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Publisher: Elsevier   (Total: 3161 journals)

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Showing 1 - 200 of 3161 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 33, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 23, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 94, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 34, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 411, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 250, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 16, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 147, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 31, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 9)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 24)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 28, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 44, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 56, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 16, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 9)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 62)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 397, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 10, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 31, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 47, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 341, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 11, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 446, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 17, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 44, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 2)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 57, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 50, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 54, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 45, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 34, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 28, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 46)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 205, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 38, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 62, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 17, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 43, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 177, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 11, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 190, SJR: 1.58, CiteScore: 3)

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Journal Cover
Neuroscience Research
Journal Prestige (SJR): 1.091
Citation Impact (citeScore): 2
Number of Followers: 9  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0168-0102
Published by Elsevier Homepage  [3161 journals]
  • Mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in
           the substantia nigra of mice with MPTP-induced Parkinson’s disease
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Yuina Kusuda, Ai Takemura, Masaki Nakano, Akihiko IshiharaAbstractWe examined whether exposure to mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the substantia nigra of a neurotoxic animal model with Parkinson’s disease. Mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride and probenecid twice a week were divided into two groups: mice with mild hyperbaric oxygen and those without. The mice with mild hyperbaric oxygen were exposed to 1317 hPa with 45% oxygen for 3 h, three times a week. The decrease in dopaminergic neurons of mice with Parkinson’s disease was inhibited by 11 weeks of exposure to mild hyperbaric oxygen. We conclude that exposure to mild hyperbaric oxygen is effective in preventing the progression of Parkinson’s disease.
       
  • Striatonigral direct pathway activation is sufficient to induce repetitive
           behaviors
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Youcef Bouchekioua, Iku Tsutsui-Kimura, Hiromi Sano, Miwako Koizumi, Kenji F. Tanaka, Keitaro Yoshida, Yutaka Kosaki, Shigeru Watanabe, Masaru MimuraAbstractPharmacological intervention in the substantia nigra is known to induce repetitive behaviors in rodents, but a direct causal relationship between a specific neural circuit and repetitive behavior has not yet been established. Here we demonstrate that optogenetic activation of dopamine D1 receptor-expressing MSNs terminals in the substantia nigra pars reticulata resulted in sustained and chronic repetitive behaviors. These data show for the first time that activation of the striatonigral direct pathway is sufficient to generate motor stereotypies.
       
  • Qualitative differences in offline improvement of procedural memory by
           daytime napping and overnight sleep: An fMRI study
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Sho K. Sugawara, Takahiko Koike, Hiroaki Kawamichi, Kai Makita, Yuki H. Hamano, Haruka K. Takahashi, Eri Nakagawa, Norihiro SadatoAbstractDaytime napping offers various benefits for healthy adults, including enhancement of motor skill learning. It remains controversial whether napping can provide the same enhancement as overnight sleep, and if so, whether the same neural underpinning is recruited. To investigate this issue, we conducted functional MRI during motor skill learning, before and after a short day-nap, in 13 participants, and compared them with a larger group (n = 47) who were tested following regular overnight sleep. Training in a sequential finger-tapping task required participants to press a keyboard in the MRI scanner with their non-dominant left hand as quickly and accurately as possible. The nap group slept for 60 min in the scanner after the training run, and the previously trained skill was subsequently re-tested. The whole-night sleep group went home after the training, and was tested the next day. Offline improvement of speed was observed in both groups, whereas accuracy was significantly improved only in the whole-night sleep group. Correspondingly, the offline increment in task-related activation was significant in the putamen of the whole-night group. This finding reveals a qualitative difference in the offline improvement effect between daytime napping and overnight sleep.
       
  • Receptive field properties of cat perigeniculate neurons correlate with
           excitatory and inhibitory connectivity to LGN relay neurons
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Hironobu Osaki, Tomoyuki Naito, Shogo Soma, Hiromichi SatoAbstractThe cat perigeniculate nucleus (PGN) is a visual sector of the thalamic reticular nucleus that consists of GABAergic neurons. It receives excitatory axon-collateral input from relay neurons of the dorsal lateral geniculate nucleus (LGN) to which it provides inhibitory input. Thus, it is usually argued that the PGN works as feedback inhibition to the LGN. At the single neuron level, however, this circuit can also provide lateral inhibition. Which inhibition dominates in the visual circuit of the thalamus has yet to be well characterized. In this study, we conducted cross-correlation analysis of single spike trains simultaneously recorded from PGN and LGN neurons in anesthetized cats. For 12 pairs of functionally connected PGN and LGN neurons with overlapped receptive fields (RF), we quantitatively compared RF properties including the spatial frequency (SF) and temporal frequency (TF) tunings of each neuron. We found the SF and TF tunings of PGN neurons and LGN neurons were similar when there was only excitatory input from the LGN neuron to the PGN neuron, but different when the PGN neuron returned inhibitory inputs back, suggesting the circuit between PGN and LGN neurons works as lateral inhibition for these properties.
       
  • A transient insulin system dysfunction in newborn rat brain followed by
           neonatal intracerebroventricular administration of streptozotocin could be
           accompanied by a labile cognitive impairment
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Zohreh Abbasi, Fatemeh Behnam-Rassouli, Mohammad Mahdi Ghahramani Seno, Masoud FereidoniAbstractThe early postnatal period is a critical period of hippocampus development, which is highly dependent on insulin receptor (IR) signaling and very important in cognitive function. The present study was conducted in order to present a model of neonatal transient brain insulin system dysfunction through finding an appropriate dose of injection of streptozotocin (STZ) during the neonatal period.Sixty male Wistar rat pups were divided into 4 groups of 15 and received intracerebroventricular saline or STZ (icv-STZ) (15, 20 and 25 μg/kg) on postnatal day 7. Gene expression of IR and target genes for IR signaling (choline acetyltransferase (ChAT) and Tau) were measured at the ages of 2 and 7 weeks. Behavioral tests were performed at the ages of 3 and 6 weeks to assess short- and long-term cognitive function. 20 μg/kg dose of icv-STZ was estimated as the optimal dose causing transient alteration in gene expression of IR, ChAT and Tau. Additionally, cognitive function of the animals restored to normal level at the age of 6 weeks. Therefore, 20 μg/kg dose of icv-STZ is proposed as a new approach to generating transient brain insulin system dysfunction associated with transient cognitive impairments at a critical postnatal period of brain development.
       
  • Modulation of hyperpolarization-activated cation current I h by volatile
           
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Yusuke Sugasawa, Masataka Fukuda, Nozomi Ando, Ritsuko Inoue, Sakura Nakauchi, Masami Miura, Kinya NishimuraAbstractVolatile anesthetics have been reported to inhibit hyperpolarization-activated cyclic-nucleotide gated channels underlying the hyperpolarization-activated cation current (Ih) that contributes to generation of synchronized oscillatory neural rhythms. Meanwhile, the developmental change of Ih has been speculated to play a pivotal role during maturation. In this study, we examined the effect of the volatile anesthetic sevoflurane, which is widely used in pediatric surgery, on Ih and on functional Ih activation kinetics of cholinergic interneurons in developing striatum. Our analyses showed that the changes in Ih of cholinergic interneurons occurred in conjunction with maturation. Sevoflurane application (1–4%) caused significant inhibition of Ih in a dose-dependent manner, and apparently slowed Ih activation. In current-clamp recordings, sevoflurane significantly decreased spike firing during the rebound activation, which is essential for responses to the sensory inputs from the cortex and thalamus. The sevoflurane-induced inhibition of Ih in striatal cholinergic interneurons may lead to alterations of the acetylcholine-dopamine balance in the neural circuits during the early postnatal period.
       
  • Generation of Pax6-IRES-EGFP knock-in mouse via the cloning-free
           CRISPR/Cas9 system to reliably visualize neurodevelopmental dynamics
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Yukiko U. Inoue, Yuki Morimoto, Mikio Hoshino, Takayoshi InoueAbstractPax6 encodes a transcription factor that plays pivotal roles in eye development, early brain patterning, neocortical arealization, and so forth. Visualization of Pax6 expression dynamics in these events could offer numerous advantages to neurodevelopmental studies. While CRISPR/Cas9 system has dramatically accelerated one-step generation of knock-out mouse, establishment of gene-cassette knock-in mouse via zygote injection has been considered insufficient due to its low efficiency. Recently, an improved CRISPR/Cas9 system for effective gene-cassette knock-in has been reported, where the native form of guide RNAs (crRNA and tracrRNA) assembled with recombinant Cas9 protein are directly delivered into mouse fertilized eggs. Here we apply this strategy to insert IRES-EGFP-pA cassette into Pax6 locus and achieve efficient targeted insertions of the 1.8 kb reporter gene. In Pax6-IRES-EGFP mouse we have generated, EGFP-positive cells reside in the eyes and cerebellum as endogenous Pax6 expressing cells at postnatal day 2. At the early embryonic stages when the embryos are transparent, EGFP-positive regions can be easily identified without PCR-based genotyping, precisely recapitulating the endogenous Pax6 expression patterns. Remarkably, at E12.5, the graded expression patterns of Pax6 in the developing neocortex now become recognizable in our knock-in mice, serving a sufficiently sensitive and useful tool to precisely visualize neurodevelopmental processes.
       
  • PRELIM II(EDI BOARD)
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s):
       
  • Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated
           neuronal death induced by status epilepticus
    • Abstract: Publication date: July 2018Source: Neuroscience Research, Volume 132Author(s): Ji-Eun Kim, Tae-Cheon KangAbstractAberrant cell cycle re-entry promotes neuronal death in various neurological diseases. Thus, cyclin-dependent kinases (CDKs) seem to be one of potential therapeutic targets to prevent neuronal loss. In the present study, we investigated the involvements of CDK4, CDK5 and p27Kip1 (an endogenous CDK inhibitor) in status epilepticus (SE)-induced neuronal death. Following SE, CDK4 expression was increased in CA1 neurons, while CDK5 was decreased. Most of TUNEL-positive neurons showed CDK4 expression, but less CDK5 expression. Flavopiridol (a CDK4 inhibitor) attenuated TUNEL signal and CDK4 expression in CA1 neurons following SE. CDK5 inhibitors did not affect these phenomena. Both flavopiridol and leptomycin B (an inhibitor of chromosome region maintenance 1) mitigated SE-induced neuronal death by inhibiting nucleocytoplasmic p27Kip1 translocation. These findings suggest that SE may lead to nucleocytoplasmic p27Kip1 export that initiates CDK4, not CDK5, induction, which an abortive and fatal cell cycle re-entry progress in CA1 neurons.
       
  • Brain mechanisms of visual long-term memory retrieval in primates
    • Abstract: Publication date: Available online 30 June 2018Source: Neuroscience ResearchAuthor(s): Masaki TakedaAbstractMemorizing events or objects and retrieving them from memory are essential for daily life. Historically, memory processing was studied in neuropsychology, in which patients provided us with insights into the brain mechanisms underlying memory. Psychological hypotheses about memory processing have been further investigated using neuroscience techniques, such as functional imaging and electrophysiology. In this article, I briefly summarize recent findings on multi-scale neural circuitry for memory at the scale of single neurons and cortical layers as well as inter-area and whole-brain interactions. The key idea which connects multi-scale neural circuits is how neuronal assemblies utilize the frequency of communication between neurons, cortical layers, and brain areas. Using findings and ideas from other cognitive function studies, I discuss the plausible communication between neurons involved in memory.
       
  • Cell death cascade and molecular therapy in ADAR2-deficient motor neurons
           of ALS
    • Abstract: Publication date: Available online 23 June 2018Source: Neuroscience ResearchAuthor(s): Takenari Yamashita, Shin KwakTAR DNA-binding protein (TDP-43) pathology in the motor neurons is the most reliable pathological hallmark of amyotrophic lateral sclerosis (ALS), and motor neurons bearing TDP-43 pathology invariably exhibit failure in RNA editing at the GluA2 glutamine/arginine (Q/R) site due to down-regulation of adenosine deaminase acting on RNA 2 (ADAR2). Conditional ADAR2 knockout (AR2) mice display ALS-like phenotype, including progressive motor dysfunction due to loss of motor neurons. Motor neurons devoid of ADAR2 express Q/R site-unedited GluA2, and AMPA receptors with unedited GluA2 in their subunit assembly are abnormally permeable to Ca2+, which results in progressive neuronal death. Moreover, analysis of AR2 mice has demonstrated that exaggerated Ca2+ influx through the abnormal AMPA receptors overactivates calpain, a Ca2+-dependent protease, that cleaves TDP-43 into aggregation-prone fragments, which serve as seeds for TDP-43 pathology. Activated calpain also disrupts nucleo-cytoplasmic transport and gene expression by cleaving molecules involved in nucleocytoplasmic transport, including nucleoporins. These lines of evidence prompted us to develop molecular targeting therapy for ALS by normalization of disrupted intracellular environment due to ADAR2 down-regulation. In this review, we have summarized the work from our group on the cell death cascade in sporadic ALS and discussed a potential therapeutic strategy for ALS.Graphical abstractGraphical abstract for this article
       
  • Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in
           Alzheimer’s disease model mouse
    • Abstract: Publication date: Available online 6 June 2018Source: Neuroscience ResearchAuthor(s): Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Xianghong Li, Feng Tian, Xia Liu, Yong Huang, Xiaowen Shi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji AbeCerebral neuroinflammation defines a novel pathway for progressing Alzheimer’s disease (AD) pathology. We investigated immunohistological changes of neuroinflammation with nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3), activated caspase-1 and interleukin-1 beta (IL-1β) in a novel AD (APP23) mice with chronic cerebral hypoperfusion (CCH) model from 4 months (M) of age, moreover, examined protective effect of galantamine. CCH strongly enhanced NLRP3, activated caspase-1 and IL-1β expressions in hippocampus and thalamus at age 12 M of AD mice. CCH also exaggerated amyloid-beta (Aβ) 40 depositions in cerebral cortex. Furthermore, CCH exacerbated a marked dissociation of neurovascular unit (NVU). These pathological changes were ameliorated by galantamine treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology including neuroinflammation, Aβ accumulations and NVU dissociation in AD mice, which was greatly protected by an allosterically potentiating ligand galantamine.Graphical abstractChronic cerebral hypoperfusion (CCH) strongly exaggerated Aβ accumulations. CCH greatly exacerbated neuroinflammation and NVU dissociation in AD mice. Primary AD pathology was greatly protected by galantamine.Graphical abstract for this article
       
  • Systemic administration of α-lipoic acid suppresses excitability of
           nociceptive wide-dynamic range neurons in rat spinal trigeminal nucleus
           caudalis
    • Abstract: Publication date: Available online 6 June 2018Source: Neuroscience ResearchAuthor(s): S. Hidaka, Y. Kanai, S. Takehana, Y. Syoji, Y. Kubota, N. Uotsu, K. Yui, Y. Shimazu, M. TakedaAbstractAlthough a modulatory role has been reported for α-lipoic acid (LA) on T-type Ca2+ channels in the nervous system, the acute effects of LA in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous LA administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from seventeen SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was significantly and dose-dependently inhibited by LA (1–100 mM, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 5 min. These inhibitory effects lasted for approximately 10 min. These results suggest that acute intravenous LA administration suppresses trigeminal sensory transmission, including nociception, via possibly blocking T-type Ca2+ channels. LA may be used as a therapeutic agent for the treatment of trigeminal nociceptive pain.
       
  • Effect of orexin-A in the arcuate nucleus on cisplatin-induced gastric
           side effects in rats
    • Abstract: Publication date: Available online 4 June 2018Source: Neuroscience ResearchAuthor(s): Feifei Guo, Luo Xu, Shengli Gao, Xiangrong Sun, Nana Zhang, Yanling GongAbstractThe most common side effects of the cancer chemotherapy drug cisplatin are nausea and vomiting. These effects are heavily influenced by orexigenic and anorexigenic peptides. We explored the effects of orexin-A on the cisplatin-treated rats and a possible mechanism for its effects on cisplatin-induced side effects. Quantitative real-time PCR was used to measure the change of prepro-orexin mRNA in the hypothalamus following cisplatin treatment. The effect of orexin-A and cisplatin on the firing rate of arcuate nucleus neurons was recorded. The effect of administration of orexin-A and a neuropeptide Y1 receptor antagonist to the arcuate nucleus on food intake, pica, and gastric motility on cisplatin treated rats were also measured. The relative expression of prepro-orexin mRNA in the hypothalamus was reduced by cisplatin. Exogenous orexin-A altered cisplatin-induced changes to the neuronal firing of gastric distension-responsive neurons, alleviated the cisplatin-induced anorexia, pica and improves the weakened gastric motility in the arcuate nucleus of rats. These effects could be partially blocked by intracerebroventricular injection (i.c.v.) of a neuropeptide Y1 receptor antagonist. These results suggest that orexin-A signaling ameliorates the gastric disorder induced by cisplatin in rats, and may act through neuropeptide Y neurons in the arcuate nucleus.
       
  • Role of the epigenetic factor Sirt7 in neuroinflammation and neurogenesis
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Nicolas Burg, Stefan Bittner, Erik EllwardtAbstractEpigenetic regulators are increasingly recognized as relevant modulators in the immune and nervous system. The class of sirtuins consists of NAD+-dependent histone deacetylases that regulate transcription. Sirtuin family member Sirt1 has already been shown to influence the disease course in an animal model of autoimmune neuroinflammation (experimental autoimmune encephalomyelitis (EAE). A role of Sirt7, a related epigenetic regulator, on immune system regulation has been proposed before, as these mice are more susceptible to develop inflammatory cardiomyopathy. Sirt7−/− animals showed no differences in clinical score compared to wild-type littermates after EAE induction with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, although we found subtle immune alterations at different phases of EAE and decreased survival of newly generated neurons in the hippocampus. Our data indicate that Sirt7 has a slight protective impact on both the adaptive immune system and neurogenesis. However, overall this epigenetic factor is not capable of impacting the acute or chronic phase of neuroinflammation.
       
  • PRELIM II(EDI BOARD)
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s):
       
  • Prolonged sleep deprivation decreases cell proliferation and immature
           newborn neurons in both dorsal and ventral hippocampus of male rats
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Yusuke Murata, Ayana Oka, Ayaka Iseki, Masayoshi Mori, Kenji Ohe, Kazunori Mine, Munechika EnjojiAbstractPrevious studies have indicated that sleep deprivation negatively affects hippocampal neurogenesis, which may explain the reason for the relation between sleep loss and depression. Increasing evidence indicates that the hippocampus is anatomically and functionally segregated along a dorsolateral (cognitive function)/ventromedial (control for mood and stress response) axis. Thus, the present study was conducted to elucidate regional differences in the adverse effects of sleep deprivation on hippocampal neurogenesis. Male Sprague-Dawley rats were subjected to sleep deprivation using the “platform on the water” method for 24- or 72-h. Quantification of hippocampal cell proliferation and immature newborn neurons was stereologically estimated using immunostaining with Ki-67 and doublecortin (DCX), respectively, by optical fractionator method. A consecutive three days of sleep deprivation significantly reduced the density of Ki-67- and DCX-immunopositive cells both in the dorsal and ventral hippocampal subgranular zone and the decrease in DCX-labeled cells was more pronounced in the ventral hippocampus than in dorsal region. Our results indicate that prolonged sleep deprivation decreases hippocampal cell proliferation and neurogenesis in both the dorsal and ventral dentate gyrus. Future studies will be needed to clarify the impact of sleep deprivation-induced decreases in hippocampal neurogenesis on the development of depression.
       
  • The Pyk2/MCU pathway in the rat middle cerebral artery occlusion model of
           ischemic stroke
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Kun Zhang, Jiajia Yan, Liang Wang, Xinying Tian, Tong Zhang, Li Guo, Bin Li, Wang Wang, Xiaoyun LiuAbstractMitochondrial dysfunction caused by Ca2+ overload plays an important role in ischemia-induced brain damage. Mitochondrial calcium uniporter (MCU), located on the mitochondrial inner membrane, is the major channel responsible for mitochondrial Ca2+ uptake. Activated proline-rich tyrosine kinase 2 (Pyk2) can directly phosphorylate MCU, which enhances mitochondrial Ca2+ uptake in cardiomyocytes. It has been suggested that the Pyk2/MCU pathway may be a novel therapeutic target in stress-induced cellular apoptosis. In this study, we explored the role of the Pyk2/MCU pathway in the ischemic brain following a stroke injury. We found that the Pyk2/MCU pathway is activated in a rat cerebral ischemia model, and is responsible for mitochondrial dysfunction and neuronal apoptosis. Inhibiting the Pyk2/MCU pathway with a Pyk2 inhibitor (PF-431396) prevented mitochondrial Ca2+ overload, mitochondrial injury, proapoptotic protein release, and cell death. Interestingly, human urinary kallidinogenase (HUK) alleviated neuronal ischemic injury by inhibiting the Pyk2/MCU pathway, suggesting that the Pyk2/MCU pathway may be a protective target for ischemic stroke treatment.
       
  • The relationship between the superior frontal cortex and alpha oscillation
           in a flanker task: Simultaneous recording of electroencephalogram (EEG)
           and near infrared spectroscopy (NIRS)
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Kota Suzuki, Yasuko Okumura, Yosuke Kita, Yuhei Oi, Haruo Shinoda, Masumi InagakiAbstractActivity in the alpha band of the electroencephalogram (EEG) reflects functional inhibition of the cerebral cortex. The superior frontal cortex (SFC) is known to control alpha activity. Based on this relationship between SFC and alpha, we hypothesized that SFC controlled alpha mediates proactive control over interference. In this study, we examined the relationship between SFC and alpha in the flanker task by simultaneously recording EEG and near infrared spectroscopy (NIRS). Forty participants performed a flanker task with occasional (compatible 75%, incompatible 25%) and successive (incompatible 100%) conditions. In the occasional condition, larger SFC activity was related to pre-stimulus alpha enhancement under occipital electrodes. This is consistent with a model in which SFC enhances pre-stimulus alpha activity, leading to proactive control over interference. However, we could not detect a correlation between SFC activity and alpha activity in the successive condition. Active inhibition may have been reduced by a need to continuously inhibit brain regions associated with the irrelevant information. This may have reduced the role of the SFC in controlling alpha activity. Based on these findings, we postulate that there are two cerebral mechanisms of proactive control over interference.
       
  • Immediate elimination of injured white matter tissue achieves a rapid
           axonal growth across the severed spinal cord in adult rats
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Takeshi Nishio, Hiroshi Fujiwara, Isaku KannoAbstractIn general, axonal regeneration is very limited after transection of adult rat spinal cord. We previously demonstrated that regenerative axons reached the lesion site within 6 h of sharp transection with a thin scalpel. However, they failed to grow across the lesion site, where injured axon fragments (axon-glial complex, AGC) were accumulated. Considering a possible role of these axon fragments as physicochemical barriers, we examined the effects of prompt elimination of the barriers on axonal growth beyond the lesion site. In this study, we made additional oblique section immediately after the primary transection and surgically eliminated the AGC (debridement). Under this treatment, regenerative axons successfully traversed the lesion site within 4 h of surgery. To exclude axonal sparing, we further inserted a pored sheet into the debrided lesion and observed the presence of fascicles of unmyelinated axons traversing the sheet through the pores by electron microscopy, indicating bona fide regeneration. These results suggest that the sequential trial of reduction and early elimination of the physicochemical barriers is one of the effective approaches to induce spontaneous and rapid regeneration beyond the lesion site.
       
  • Corticomuscular coherence reflects somatosensory feedback gains during
           motor adaptation
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Shoko Kasuga, Natsumi Momose, Junichi Ushiyama, Junichi UshibaAbstractBeta-band corticomuscular coherence (CMC) observed between the sensorimotor cortex activity and contracting muscle is declaratively described as a neurophysiological reflection of sensorimotor binding. However, much remains unknown about the functional meaning of ‘sensorimotor binding.’ The efficacy of information binding in the sensorimotor system is assumed to be influenced by the gain of the feedback controller, which is regulated through a process that may in part be implemented in the primary sensorimotor cortex (SM1). Thus, we predicted that CMC is modulated together with feedback gains during motor learning. We examined this hypothesis using a hand-reaching adaptation task under a novel dynamical environment. CMC modulation was assessed before and after adaptation, and feedback gains were probed by long latency triggered muscle reactions. Overall, we found that CMC significantly decreased during the adaptation period, and such CMC decrease was associated with the decreased long latency reflexes. These results suggest that CMC has a related function to modulation of feedback gains. Our findings provided an electrophysiological hallmark of the sensorimotor binding process, which was stated as a function of CMC but poorly understood.
       
  • Activity changes in the left superior temporal sulcus reflect the effects
           of childcare training on young female students’ perceptions of
           infants’ negative facial expressions
    • Abstract: Publication date: June 2018Source: Neuroscience Research, Volume 131Author(s): Ayahito Ito, Katsuko Niwano, Motoko Tanabe, Yosuke Sato, Toshikatsu FujiiAbstractIn many developed countries, the number of infants who experience non-parent childcare is increasing, and the role of preschool teachers is becoming more important. However, little attention has been paid to the effects of childcare training on students who are studying to become preschool teachers. We used functional magnetic resonance imaging (fMRI) to investigate whether and how childcare training affects brain responses to infants’ facial expressions among young females studying to become preschool teachers. Twenty-seven subjects who attended a childcare training session (i.e., the experimental group) and 28 subjects who did not attend the training (i.e., the control group) participated in this study. The participants went through fMRI scanning twice: before and after the childcare training session. They were presented with happy, neutral, and sad infant faces one by one during fMRI scanning. The present neuroimaging results revealed that the activity patterns of the left superior temporal sulcus (STS) for sad faces were modulated by the interaction between the time point of the data collection and group differences. The present results are the first to highlight the effects of childcare training on the human brain.
       
  • Np95/Uhrf1 regulates tumor suppressor gene expression of neural
           stem/precursor cells, contributing to neurogenesis in the adult mouse
           brain
    • Abstract: Publication date: Available online 31 May 2018Source: Neuroscience ResearchAuthor(s): Naoya Murao, Shuzo Matsubara, Taito Matsuda, Hirofumi Noguchi, Tetsuji Mutoh, Masahiro Mutoh, Haruhiko Koseki, Masakazu Namihira, Kinichi NakashimaAbstractAdult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.
       
  • In utero electroporation-based translating ribosome affinity purification
           identifies age-dependent mRNA expression in cortical pyramidal neurons
    • Abstract: Publication date: Available online 29 May 2018Source: Neuroscience ResearchAuthor(s): Tianxiang Huang, Lena H. Nguyen, Tiffany V. Lin, Xuan Gong, Longbo Zhang, Gi Bum Kim, Matthew R. Sarkisian, Joshua J. Breunig, Angelique BordeyAbstractWe combined translating ribosome affinity purification (TRAP) with in utero electroporation (IUE), called iTRAP to identify the molecular profile of specific neuronal populations during neonatal development without the need for viral approaches and FACS sorting. We electroporated a plasmid encoding EGFP-tagged ribosomal protein L10a at embryonic day (E) 14–15 to target layer 2–4 cortical neurons of the somatosensory cortex. At three postnatal (P) ages—P0, P7, and P14—when morphogenesis occurs and synapses are forming, TRAP and molecular profiling was performed from electroporated regions. We found that ribosome bound (Ribo)-mRNAs from ∼7300 genes were significantly altered over time and included classical neuronal genes known to decrease (e.g., Tbr1, Dcx) or increase (e.g., Eno2, Camk2a, Syn1) as neurons mature. This approach led to the identification of specific developmental patterns for Ribo-mRNAs not previously reported to be developmentally regulated in neurons, providing rationale for future examination of their role in selective biological processes. These include upregulation of Lynx1, Nrn1, Cntnap1 over time; downregulation of St8sia2 and Draxin; and bidirectional changes to Fkbp1b. iTRAP is a versatile approach that allows researchers to easily assess the molecular profile of specific neuronal populations in selective brain regions under various conditions, including overexpression and knockdown of target genes, and in disease settings.
       
  • Non-structured spike sequences of hippocampal neuronal ensembles in awake
           animals
    • Abstract: Publication date: Available online 26 May 2018Source: Neuroscience ResearchAuthor(s): Takuya SasakiAbstractThe hippocampal network generates synchronized spikes of a large population of pyramidal neurons associated with sharp-wave ripples in local field potential signals. Ample evidence demonstrates that the synchronized spikes are created by sequential activation of hippocampal place cells that correspond to the animal’s past or future trajectories and are hypothesized to play instrumental roles in mnemonic functions. However, not all place-cell spike sequences are precisely organized, and some sequences are composed of spikes from non-spatial cells, implying that not all hippocampal synchronized events directly replicate learned behavioral episodes. While less attention has been given to such non-ordered spike sequences, variable and dynamic selection of active neuronal assemblies may be optimal mechanisms for rapidly reorganizing functional circuits and self-developing novel representations to enable flexible decision-making processes. We recently showed that specific neurons, including both spatial and non-spatial cells, are preferentially recruited in synchronous events for particular time periods, suggesting that there are temporally fluctuating background states of the hippocampal network that determine active neuronal ensembles. Based on recent reports, this review discusses potential roles of the low-fidelity, heterogeneous repertoire of synchronized spike sequences of hippocampal neurons.
       
  • Serotonergic projections to the ventral respiratory column from raphe
           nuclei in rats
    • Abstract: Publication date: Available online 24 May 2018Source: Neuroscience ResearchAuthor(s): Ryosuke Morinaga, Nobuaki Nakamuta, Yoshio YamamotoAbstractThe ventral respiratory column (VRC) generates rhythmical respiration and is divided into four compartments: the Bötzinger complex (BC), pre-Bötzinger complex (PBC), rostral ventral respiratory group (rVRG), and caudal ventral respiratory group (cVRG). Serotonergic nerve fibers are densely distributed in the rostral to caudal VRC and serotonin would be one of the important modulators for the respiratory control in the VRC. In the present study, to elucidate detailed distribution of serotonergic neurons in raphe nuclei projecting to the various rostrocaudal levels of VRC, we performed combination of retrograde tracing technique by cholera toxin B subunit (CTB) with immunohistochemistry for tryptophan hydroxylase 2 (TPH2). The double-immunoreactive neurons with CTB and TPH2 were distributed in the both rostral and caudal raphe nuclei, i.e. dorsal raphe nucleus, raphe magnus nucleus, gigantocellular reticular nucleus alpha and ventral parts, lateral paragigantocellular nucleus, parapyramidal area, raphe obscurus nucleus, and raphe pallidus nucleus. The distributions of double-immunoreactive neurons were similar among injection groups of BC, PBC, anterior rVRG, and posterior rVRG/cVRG. In conclusion, serotonergic neurons in both rostral and caudal raphe nuclei projected throughout the VRC and these serotonergic projections may contribute to respiratory responses to various environmental and vital changes.
       
  • Effects of propofol on IPSCs in CA1 and dentate gyrus cells of rat
           hippocampus: Propofol effects on hippocampal cells’ IPSCs
    • Abstract: Publication date: Available online 17 May 2018Source: Neuroscience ResearchAuthor(s): Masanori Ishiguro, Suguru Kobayashi, Kiyoji Matsuyama, Takashi NagamineAbstractPropofol (2, 6-diisopropylphenol) is one of the most popular intravenous anesthetic agents. In this study, we compared the effects of propofol on inhibitory postsynaptic currents (IPSCs) induced by single and paired electrical stimulations in CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices using the whole cell patch-clamp technique. In the absence of propofol, the amplitude of evoked IPSC by single stimulation and decay time constants were stable in both CA1-PCs and DG-GCs for 30 min. Propofol (1 μM and 10 μM) increased both IPSC amplitude in CA1-PCs, but not in DG-GCs. Further, using a paired pulse stimulation protocol, the ratio of IPSC amplitudes (the second response: A2/the first response: A1) was increased by propofol in CA1, but not in DG-GCs. These results suggest that propofol selectively affects IPSCs in CA1-PCs, which is similar to previously reported actions of benzodiazepines.
       
  • Effects of SC99 on cerebral ischemia-perfusion injury in rats: Selective
           modulation of microglia polarization to M2 phenotype via inhibiting
           JAK2-STAT3 pathway
    • Abstract: Publication date: Available online 12 May 2018Source: Neuroscience ResearchAuthor(s): Yiping Ding, Jinhong Qian, Haiying Li, Haitao Shen, Xiang Li, Yan Kong, Zhuan Xu, Gang ChenAbstractInhibition of Janus kinases 2-Signal transducers and activators of transcription3 (JAK2-STAT3) pathway has been shown to exert anti-inflammatory actions. SC99, a novel specific inhibitor targeting JAK2-STAT3 pathway, has been verified to negatively modulate platelet activation and aggregation in vitro. In current study, a middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in Sprague Dawley rats and primary cultured microglia was exposed to oxygen and glucose deprivation (OGD/R) in vitro. Different dosages were employed to detect the effects of SC99 on cerebral ischemia-perfusion (I/R) injury and evaluate the underlying mechanisms. Our results showed that intracerebroventricular injection of SC99 (10 mmol/L, 15 μL) produced an effective inhibitory effect on the phosphorylation of JAK2 and STAT3. Correspondingly, SC99 ameliorated neuronal apoptosis and degeneration, neurobehavioral deficits, inflammatory response and brain edema. And SC99 promoted microglia polarization to an anti-inflammatory M2 phenotype. We concluded that SC99 could alleviate brain damage and play an anti-inflammatory action by promoting microglia polarization to an anti-inflammatory phenotype after I/R injury, which provides an emerging and promising alternative to protect the brain against MCAO/R injury in the future investigations.
       
  • Role of C1 neurons in anti-inflammatory reflex: Mediation between
           afferents and efferents
    • Abstract: Publication date: Available online 8 May 2018Source: Neuroscience ResearchAuthor(s): Chikara Abe, Tsuyoshi InoueAbstractNeuroimmune communication, the connection between the autonomic regulatory pathway and immune cells, has been implicated in the regulation of immune function and inflammation. The role of afferents (vagal afferent and somatic sensory nerves) and efferents (autonomic nervous and hypothalamic-pituitary-adrenal systems) in the inflammatory reflex has been well studied; however, the central pathway remains unknown. C1 neurons include both catecholaminergic and glutamatergic neurons, which are located in the rostral ventrolateral medulla. C1 neurons project to the spinal cord, dorsal motor nucleus of the vagus, and hypothalamus to regulate the sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems, respectively. Because C1 neurons respond to stressors, including inflammation, hypotension, hypoxia, and hypoglycemia, it is believed that the autonomic regulatory pathway, via C1 neurons, contributes to the maintenance of physiological homeostasis. Recently, selective neural manipulation has revealed that C1 neurons participate in restraint stress-induced anti-inflammation, and protection against acute kidney injury has been attributed to stress-induced sympathoexcitation through C1 neurons. We focus here on the role of C1 neurons, which act as mediators between afferents and efferents, in the anti-inflammatory pathway.
       
  • Performance monitoring in the medial frontal cortex and related neural
           
    • Abstract: Publication date: Available online 27 April 2018Source: Neuroscience ResearchAuthor(s): Taihei Ninomiya, Atsushi Noritake, Markus Ullsperger, Masaki IsodaAbstractAction is a key channel for interacting with the outer world. As such, the ability to monitor actions and their consequences – regardless as to whether they are self-generated or other-generated – is of crucial importance for adaptive behavior. The medial frontal cortex (MFC) has long been studied as a critical node for performance monitoring in nonsocial contexts. Accumulating evidence suggests that the MFC is involved in a wide range of functions necessary for one’s own performance monitoring, including error detection, and monitoring and resolving response conflicts. Recent studies, however, have also pointed to the importance of the MFC in performance monitoring under social conditions, ranging from monitoring and understanding others’ actions to reading others’ mental states, such as their beliefs and intentions (i.e., mentalizing). Here we review the functional roles of the MFC and related neural networks in performance monitoring in both nonsocial and social contexts, with an emphasis on the emerging field of a social systems neuroscience approach using macaque monkeys as a model system. Future work should determine the way in which the MFC exerts its monitoring function via interactions with other brain regions, such as the superior temporal sulcus in the mentalizing system and the ventral premotor cortex in the mirror system.
       
  • Vascular Endothelial Growth Factor Improves the Cognitive Decline of
           Alzheimer’s Disease via Concurrently Inducing the Expression of ADAM10
           and Reducing the Expression of β-site APP cleaving enzyme 1 in Tg2576
           mice
    • Abstract: Publication date: Available online 24 April 2018Source: Neuroscience ResearchAuthor(s): Hongwei Guo, Deyu Xia, Shaohua Liao, Bing Niu, Jigang Tang, Huaiqiang Hu, Hairong Qian, Bingzhen CaoAlzheimer’s disease (AD) is primarily characterized by the production and deposit of β-amyloid protein (Aβ) in β-amyloid plaques (APs). On this basis, we investigated whether vascular endothelial growth factor (VEGF), a growth factor with important neuroprotective activity, may provide a therapeutic opportunity for treating AD. We initially found that the expression and production of VEGF was downregulated in the brains of Tg2576 mice during the course of AD development and progression. Restoring VEGF in the brains of Tg2576 mice antagonized the production and deposit of Aβ in Tg2576 mice. The addition of VEGF concurrently increased the expression of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and decreased the expression of β-site APP cleaving enzyme 1 (BACE1), which contributes to the enhanced clearance of Aβ in vivo. By decreasing the production and deposit of Aβ, VEGF improved the cognitive decline of Tg2576 mice. These observations provide a novel implication for VEGF as a therapeutic approach for the treatment of AD.Graphical abstractGraphical abstract for this article
       
  • Upregulation of Cav3.2 T-type calcium channels in adjacent intact L4
           dorsal root ganglion neurons in neuropathic pain rats with L5 spinal nerve
           ligation
    • Abstract: Publication date: Available online 21 April 2018Source: Neuroscience ResearchAuthor(s): Qing-Ying Liu, Wen Chen, Shuang Cui, Fei-Fei Liao, Ming Yi, Feng-Yu Liu, You WanAbstractBesides the injured peripheral dorsal root ganglion (DRG) neurons, the adjacent intact DRG neurons also have important roles in neuropathic pain. Ion channels including Cav3.2 T-type calcium channel in the DRG neurons are important in the development of neuropathic pain. In the present study, we aimed to examine the expression of Cav3.2 T-type calcium channels in the intact DRG neurons in neuropathic pain. A neuropathic pain model of rat with lumbar 5 (L5) spinal nerve ligation (SNL) was established, in which the L4 DRG was separated from the axotomized L5 DRG, and the molecular, morphological and electrophysiological changes of Cav3.2 T-type calcium channels in L4 DRG neurons were investigated. Western blotting showed that total and membrane protein levels of Cav3.2 in L4 DRG neurons increased, and voltage-dependent patch clamp recordings revealed an increased T-type current density with a curve shift to the left in steady-state activation in the acutely isolated L4 DRG neurons in neuropathic pain rats. Immunofluorescent staining further showed that the membrane expression of Cav3.2 increased in CGRP-, IB4-positive small neurons and NF200-positive large ones. In conclusion, the membrane expression and the function of Cav3.2 T-type calcium channels are increased in the intact L4 DRG neurons in neuropathic pain rats with peripheral nerve injury like SNL.
       
  • Vowel-speech versus pure-tone processing in healthy subjects
    • Abstract: Publication date: Available online 6 April 2018Source: Neuroscience ResearchAuthor(s): Hiroko Iino, Katsuya Ohta, Keiko Hara, Miho Miyajima, Minoru Hara, Eisuke Matsushima, Masato MatsuuraAbstractTo investigate the characteristics of speech perception, we evaluated the differences in mismatch negativity (MMN) between vowel change and frequency change. Additionally, we examined the effects of gender, age, and educational length on MMN. Forty healthy adults (21 females), who were native Japanese speakers, participated in the study. A Japanese vowel-speech pair (standard/a/vs. deviant/o/) and a pure-tone pair (standard 1000 Hz vs. deviant 1050 Hz) were constructed. MMN elicited by vowel-speech sounds was larger and earlier compared with pure-tone sounds. Larger and earlier MMNs for vowel-speech sounds than for pure-tone sounds suggest different processing of linguistically relevant information at the early stage in the auditory cortex. In conclusion, the factors influencing on MMN are different between vowel-speech sounds and pure-tone sounds.
       
  • Local traction force in the proximal leading process triggers nuclear
           translocation during neuronal migration
    • Abstract: Publication date: Available online 5 April 2018Source: Neuroscience ResearchAuthor(s): Hiroki Umeshima, Ken-ichi Nomura, Shuhei Yoshikawa, Marcel Hörning, Motomu Tanaka, Shinya Sakuma, Fumihito Arai, Makoto Kaneko, Mineko KengakuAbstractSomal translocation in long bipolar neurons is regulated by actomyosin contractile forces, yet the precise spatiotemporal sites of force generation are unknown. Here we investigate the force dynamics generated during somal translocation using traction force microscopy. Neurons with a short leading process generated a traction force in the growth cone and counteracting forces in the leading and trailing processes. In contrast, neurons with a long leading process generated a force dipole with opposing traction forces in the proximal leading process during nuclear translocation. Transient accumulation of actin filaments was observed at the dipole center of the two opposing forces, which was abolished by inhibition of myosin II activity. A swelling in the leading process emerged and generated a traction force that pulled the nucleus when nuclear translocation was physically hampered. The traction force in the leading process swelling was uncoupled from somal translocation in neurons expressing a dominant negative mutant of the KASH protein, which disrupts the interaction between cytoskeletal components and the nuclear envelope. Our results suggest that the leading process is the site of generation of actomyosin-dependent traction force in long bipolar neurons, and that the traction force is transmitted to the nucleus via KASH proteins.
       
  • Elavl3 regulates neuronal polarity through the alternative splicing of an
           embryo-specific exon in AnkyrinG
    • Abstract: Publication date: Available online 31 March 2018Source: Neuroscience ResearchAuthor(s): Yuki Ogawa, Junji Yamaguchi, Masato Yano, Yasuo Uchiyama, Hirotaka James OkanoAbstractAlternative splicing of RNAs diversifies the functionalities of proteins, and it is optimized for each cell type and each developmental stage. nElavl (composed of Elavl2, Elavl3, and Elavl4) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Recent studies revealed that Elavl3 knockout (Elavl3−/−) mice completely lost the expression of nElavl proteins in the Purkinje cells and exhibited cerebellar dysfunction. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elavl3−/− mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions. We revealed that exon 34 of AnkyrinG was normally included in immature neurons and was mostly excluded in mature neurons; however, it was included in the cerebella of Elavl3−/− mice even in adulthood. In the Purkinje cells of adult Elavl3−/− mice, the length of the AnkyrinG-positive region shortened and somatic organelles leaked into the axons. These results suggested that exon 34 of AnkyrinG is an embryonic-stage-preferential exon that should be excluded from mature neurons and that Elavl3 regulates neuronal polarity through alternative splicing of this exon.
       
  • Therapeutic time window of anti-high mobility group box-1 antibody
           administration in mouse model of spinal cord injury
    • Abstract: Publication date: Available online 28 March 2018Source: Neuroscience ResearchAuthor(s): Masahide Nakajo, Naohiro Uezono, Hideyuki Nakashima, Hidenori Wake, Setsuro Komiya, Masahiro Nishibori, Kinichi NakashimaAbstractSpinal cord injury (SCI) is a devastating neurologic disorder that often leads to permanent disability, and there is no effective treatment for it. High mobility group box-1 (HMGB1) is a damage-associated molecular protein that triggers sterile inflammation upon injuries. We have previously shown that two administrations of neutralizing monoclonal antibody (mAb) against HMGB1 (immediately after (0 h) and 6 h after) SCI dramatically improves functional recovery after SCI in mice. However, when considering clinical application, 0 h after SCI is not practical. Therefore, in this study, we examined the therapeutic time window of the mAb administration. Injection at 3 h after SCI significantly improved the functional recovery comparably to injection immediately after SCI, while injection at 6 h was less effective, and injection at 9 or 12 h had no therapeutic effect. We also found beneficial effects of injection at 3 h after injury on blood-spinal cord barrier maintenance, inflammatory-related gene expression and preservation of the damaged spinal cord tissue. Taken together, our results suggest that a single administration of anti-HMGB1 mAb within a proper time window could be a novel and potential therapeutic strategy for SCI.
       
  • Neuroimaging correlates of narcolepsy with cataplexy: A systematic review
    • Abstract: Publication date: Available online 23 March 2018Source: Neuroscience ResearchAuthor(s): Masataka Wada, Masaru Mimura, Yoshihiro Noda, Shotaro Takasu, Eric Plitman, Makoto Honda, Akiyo Natsubori, Kamiyu Ogyu, Ryosuke Tarumi, Ariel Graff-Guerrero, Shinichiro NakajimaAbstractRecent developments in neuroimaging techniques have advanced our understanding of biological mechanisms underpinning narcolepsy. We used MEDLINE to retrieve neuroimaging studies to compare patients with narcolepsy and healthy controls. Thirty-seven studies were identified and demonstrated several replicated abnormalities: (1) gray matter reductions in superior frontal, superior and inferior temporal, and middle occipital gyri, hypothalamus, amygdala, insula, hippocampus, cingulate cortex, thalamus, and nucleus accumbens, (2) decreased fractional anisotropy in white matter of fronto-orbital and cingulate area, (3) reduced brain metabolism or cerebral blood flow in middle and superior frontal, and cingulate cortex (4) increased activity in inferior frontal gyri, insula, amygdala, and nucleus accumbens, and (5) N-acetylaspartate/creatine-phosphocreatine level reduction in hypothalamus. In conclusion, all the replicated findings are still controversial due to the limitations such as heterogeneity or size of the samples and lack of multimodal imaging or follow-up. Thus, future neuroimaging studies should employ multimodal imaging methods in a large sample size of patients with narcolepsy and consider age, duration of disease, age at onset, severity, human leukocyte antigen type, cerebrospinal fluid hypocretin levels, and medication intake in order to elucidate possible neuroimaging characteristic of narcolepsy and identify therapeutic targets.
       
  • Characterization of mouse chorda tympani responses evoked by stimulation
           of anterior or posterior fungiform taste papillae
    • Abstract: Publication date: Available online 23 March 2018Source: Neuroscience ResearchAuthor(s): Stuart A. McCaugheyAbstractDifferent gustatory papilla types vary in their locations on the tongue. Distinctions have often made between types, but variation within fungiform papillae has seldom been explored. Here, regional differences in fungiform papillae were investigated by flowing solutions selectively over either an anterior fungiform (AF, tongue tip) or a posterior fungiform (PF, middle third) region as taste-evoked activity was measured in the chorda tympani nerve of C57BL/6J (B6) mice. Significantly larger responses were evoked by NaCl applied to the AF than PF region, and the ENaC blocker amiloride reduced the NaCl response size only for the former. Umami synergy, based on co-presenting MSG and IMP, was larger for the AF than PF region. The regions did not differ in response size to sour chemicals, but responses to l-lysine, l-arginine, sucrose, and tetrasodium pyrophosphate were larger for the AF than PF region. Thus, fungiform papillae on the tongue tip differed from those found further back in their transduction mechanisms for salty and umami compounds. Gustatory sensitivity also showed regional variation, albeit with a complex relationship to palatability and taste quality. Overall, the data support a regional organization for the mouse tongue, with different functional zones for the anterior, middle, and posterior thirds.
       
  • Behavioral evaluation of auditory stream segregation in rats
    • Abstract: Publication date: Available online 23 March 2018Source: Neuroscience ResearchAuthor(s): Takahiro Noda, Hirokazu TakahashiAbstractPerceptual organization of sound sequences into separate sound sources or streams is called auditory stream segregation. Neural substrates for this process in both the spectral and temporal domains remain to be elucidated. Despite abundant knowledge about their auditory physiology, behavioral evidence for auditory streaming in rodents is still limited. We provided behavioral evidence for auditory streaming in the go/no-go discrimination task, but not in the two-alternative choice task. In the go/no-go discrimination phase, rats were able to discriminate different rhythms corresponding to segregated or integrated tone sequences in both short inter-tone interval (ITI) and long ITI conditions. Nevertheless, performance was poorer in the long ITI group. In probe testing, which assessed the ability to discriminate one of the segregated tone sequences from ABA- tone sequences, the detection rate increased with the difference in frequency (ΔF) for short (100 ms), but not long (200 ms) ITIs. Our results indicate that auditory streaming in rats on both the spectral and temporal features in the ABA- tone paradigm is qualitatively analogous to that observed in human psychophysics studies. This suggests that rodents are a valuable model for investigating the neural substrates of auditory streaming.
       
  • Salivary alpha-amylase and cortisol responsiveness to stress in first
           episode, drug-naïve patients with panic disorder
    • Abstract: Publication date: Available online 14 March 2018Source: Neuroscience ResearchAuthor(s): Mario Altamura, Salvatore Iuso, Angela Balzotti, Girolamo Francavilla, Andrea Dimitri, Giuseppe Cibelli, Antonello Bellomo, Annamaria PetitoAbstractReported findings on reactivity to stress of the sympathetic-adreno-medullar (SAM) and hypothalamic-pituitary-adrenal (HPA) systems in panic disorder (PD) are very variable. This inconsistency may be explained by differences in treatment exposure, illness duration and emotion regulation strategies. The present study examined the reactivity to mental stress of the SAM and HPA axes in a sample of first episode, drug naïve patients with PD which avoids confounds of medications exposure and illness chronicity. Activation of the SAM axis was evaluated by dosage of salivary alpha-amylase (sAA) and heart rate. Activation of the HPA axis was tested by dosage of salivary cortisol. Psychological assessments were done by the Self-Rating Depression Scale, the Self-Rating Anxiety Scale, the State-Trait Anxiety Inventory, the Cope Orientation to Problems Experienced (COPE) Inventory and the 16 Personality Factor Questionnaire (16PF). Patients showed reduced sAA stress reactivity, higher baseline cortisol levels and a more rapid decrease in stress cortisol levels as compared with controls. A significant correlation was found between active coping strategies and cortisol levels (response to stress). The findings suggest that blunted SAM stress reactivity and a rapid decrease in stress cortisol levels reflect traits that may enhance vulnerability to psychopathology in patients with PD.
       
  • Optical measurement of glutamate in slice preparations of the mouse retina
    • Abstract: Publication date: Available online 6 March 2018Source: Neuroscience ResearchAuthor(s): M. Ohkuma, M. Kaneda, S. Yoshida, A. Fukuda, E. MiyachiAbstractSignaling by glutamatergic synapses plays an important role in visual processing in the retina. In this study, we used an enzyme-linked fluorescence assay system to monitor the dynamics of extracellular glutamate in a slice preparation from the mouse retina. High K stimulation induced an elevation of fluorescence in the inner plexiform layer (IPL) of the retina when glutamate transporters were inhibited by dl-threo-β-benzyloxyaspartic acid (TBOA). The high K-induced fluorescence signals in the IPL were inhibited by the calcium channel blocker Cd2+. Blockade of GABAergic and glycinergic circuits by picrotoxin and strychnine also elevated the fluorescence signals in the IPL. Thus, the enzyme-linked fluorescence assay system might be useful for monitoring the bulk concentration of extracellular glutamate released by synapses in the inner retina.
       
  • Loss of GPRC5B impairs synapse formation of Purkinje cells with cerebellar
           nuclear neurons and disrupts cerebellar synaptic plasticity and motor
           learning
    • Abstract: Publication date: Available online 23 February 2018Source: Neuroscience ResearchAuthor(s): Takamitsu Sano, Ayako Kohyama-Koganeya, Masami O. Kinoshita, Tetsuya Tatsukawa, Chika Shimizu, Eriko Oshima, Kazuyuki Yamada, Tung Dinh Le, Takumi Akagi, Koujiro Tohyama, Soichi Nagao, Yoshio HirabayashiAbstractGPRC5B is a membrane glycoprotein robustly expressed in mouse cerebellar Purkinje cells (PCs). Its function is unknown. In Gprc5b−/− mice that lack GPRC5B, PCs develop distal axonal swellings in deep cerebellar nuclei (DCN). Numerous misshapen mitochondria, which generated excessive amounts of reactive oxygen species (ROS), accumulated in these distal axonal swellings. In primary cell cultures of Gprc5b−/− PCs, pharmacological reduction of ROS prevented the appearance of such swellings. To examine the physiological role of GPRC5B in PCs, we analyzed cerebellar synaptic transmission and cerebellum-dependent motor learning in Gprc5b−/− mice. Patch-clamp recordings in cerebellum slices in vitro revealed that the induction of long-term depression (LTD) at parallel fiber-PC synapses was normal in adult Gprc5b−/− mice, whereas the induction of long-term potentiation (LTP) at mossy fiber-DCN neuron synapses was attenuated in juvenile Gprc5b−/− mice. In Gprc5b−/− mice, long-term motor learning was impaired in both the rotarod test and the horizontal optokinetic response eye movement (HOKR) test. These observations suggest that GPRC5B plays not only an important role in the development of distal axons of PCs and formation of synapses with DCN neurons, but also in the synaptic plasticity that underlies long-term motor learning.
       
  • Local anesthetic effect of docosahexaenoic acid on the nociceptive
           jaw-opening reflex in rats
    • Abstract: Publication date: Available online 23 February 2018Source: Neuroscience ResearchAuthor(s): Kazuki Mitome, Shiori Takehana, Katsuo Oshima, Yoshihito Shimazu, Mamoru TakedaAbstractAlthough docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1–5 x threshold). At 3 x threshold, local administration of DHA (0.1, 10 and 25 mM) dose-dependently inhibited the dEMG response, and lasted 40 min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10 min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25 mM) was almost equal to the local anesthetic, 1% lidocaine (37 mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception.
       
  • TNFR2 mediated TNF-α signaling and Nf-κB activation in hippocampus of
           1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice
    • Abstract: Publication date: Available online 23 February 2018Source: Neuroscience ResearchAuthor(s): Nabanita Ghosh, Soham Mitra, Priyobrata Sinha, Nilkanta Chakrabarti, Arindam BhattacharyyaAbstract1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) −induced neuroinflammation and its impact in hippocampus remain elusive till date. Our present study includes the time dependent changes of inflammatory molecules in mouse hippocampus during MPTP treatment. MPTP treatment increased level of TNF-α, enhanced expression of TNFR2 along with PI3 kinase (PI3K) induced phosphorylation of Akt resulting in persistent nuclear factor-κB (NF-κB) activation. The expressions gradually increased from Day1 post-MPTP treatment, maximally at Day3 post-treatment. MPTP induced translocation of p65 and p52, two subunits of NF-κB family, to nucleus where they had been found to dimerize. Therefore, MPTP induced TNF-α signaling through TNFR2 mediated pathway and recruited p65-p52 dimer in hippocampal nucleus which is reported to have protective effect on hippocampal neurons indicated by unchanged neuronal count in hippocampus in treated groups with respect to control. Our finding suggests that this unique NF-κB dimer plays some role in providing inherent protection to hippocampus during MPTP-treatment.
       
  • Monitoring brain neuronal activity with manipulation of cardiac events in
           a freely moving rat
    • Abstract: Publication date: Available online 15 February 2018Source: Neuroscience ResearchAuthor(s): Yu Shikano, Yuji Ikegaya, Takuya SasakiAbstractBehavioral and cognitive studies have demonstrated that brain functions are affected by the activity states of the peripheral organs, such as the cardiac and respiratory systems. However, detailed neurophysiological mechanisms underlying the body-brain interactions remain unknown. In this study, we developed a method for manipulating activity levels of the heart using direct cardiac stimulation and vagus nerve stimulation that can be combined with recording cerebral local field potentials using a microdrive system, electrocardiograms, electromyograms, in a freely moving rat. With this method, the electrical stimulation to the heart increases heart rates up to 14 Hz, whereas the vagus nerve stimulation decreases heart rates to 3 Hz. Transient electrical artifacts arising from the peripheral stimulation are not contaminated in cortical local field potential signals low-pass filtered at 150 Hz and distinguishable from extracellular multiunit signals. The technique will contribute to understanding the neurophysiological correlate of mind-body associations in health and disease.
       
  • The differential roles of PEA15 phosphorylations in reactive astrogliosis
           and astroglial apoptosis following status epilepticus
    • Abstract: Publication date: Available online 10 February 2018Source: Neuroscience ResearchAuthor(s): Jin-Young Park, Tae-Cheon KangAbstractUp to this day, the roles of PEA15 expression and its phosphorylation in seizure-related events have not been still unclear. In the present study, we found that PEA15 was distinctly phosphorylated in reactive astrocytes and apoptotic astrocytes in the rat hippocampus following LiCl-pilocarpine-induced status epilepticus (SE, a prolonged seizure activity). PEA15-serine (S) 104 phosphorylation was up-regulated in reactive astrocytes following SE, although PEA15 expression and its S116 phosphorylation were unaltered. Bisindolylmaleimide (BIM), a protein kinase C (PKC) inhibitor, attenuated SE-induced reactive astrogliosis, but phorbol 12-myristate 13-acetate (PMA, a PKC activator) aggravated it. Unlike reactive astrocytes, PEA15-S116 phosphorylation was reduced in apoptotic astrocytes. However, PEA15 expression and its S104 phosphorylation were unchanged in apoptotic astrocyte. Neither BIM nor PMA affected SE-induced astroglial apoptosis. PEA15 expression and its phosphorylations were not relevant to SE-induced CA1 neuronal death. These findings indicate that PEA15-S104 and S116 phosphorylations may play a role in reactive astrogliosis and prevention of astroglial apoptosis, respectively. Therefore, we suggest that the selective manipulation of PEA15 phosphorylations may regulate apoptotic and/or proliferative signals in astrocytes.
       
  • Ethological and multi-behavioral analysis of learning and memory
           performance in laboratory rodent models
    • Abstract: Publication date: Available online 9 February 2018Source: Neuroscience ResearchAuthor(s): Hiroyuki Arakawa, Yoshio IguchiAbstractBehavioral studies using animal models have widely contributed to advancing our understanding of the neuroregulatory mechanisms of human cognitive states and disorders. A variety of behavioral tests and theoretical models have been developed that provide a standardized toolbox of behavioral test paradigms available to researchers, and thus allow rapid progress in studies of the molecular-genetic bases of behavior relevant to neurocognitive diseases. However, a growing effort to utilize standardized paradigms has overlooked the diverse behavioral characteristics of test rodents expressed in standardized test situations. This review describes two popular test paradigms for cognitive assessment in rodents: social recognition and fear conditioning tasks. An extensive assessment of observed behavior during testing indicates a need to further elucidate the sequential strategic processes employed by test animals in conjunction with the use of standardized test settings and dependent variables. The present study calls specific attention to the considerable but improvable problem of the appropriateness and applicability of these standardized test paradigms; it thereby unravels the essential contribution of multi-behavioral assessment to further advancing neuroscience research using rodent behavioral models.
       
  • Calcium-binding protein, secretagogin, specifies the microcellular
           tegmental nucleus and intermediate and ventral parts of the cuneiform
           nucleus of the mouse and rat
    • Abstract: Publication date: Available online 3 February 2018Source: Neuroscience ResearchAuthor(s): Toshio Kosaka, Katsuko KosakaAbstractSecretagogin (SCGN) is a recently discovered calcium binding protein of the EF hand family, cloned from β cells of pancreatic island of Langerhans and endocrine cells of the gastrointestinal gland. SCGN characterizes some particular neuron groups in various regions of the nervous system and is considered as one of the useful neuron subpopulation markers. In the present study we reported that SCGN specifically labelled a particular neuronal cluster in the brainstem of the mice and rats. The comparison of the SCGN immunostaining with the choline acetyltransferase immunostaining and acetylcholinesterase staining clearly indicated that the particular cluster of SCGN positive neurons corresponded to the microcellular tegmental nucleus (MiTg) and the ventral portion of the cuneiform nucleus (CnF), both of which are components of the isthmus. The analyses in mice indicated that SCGN positive neurons in the MiTg and CnF were homogeneous in size and shape, appearing to compose a single complex: their somata were small comparing with the adjacent cholinergic neurons in the pedunculotegmantal nucleus, 10.5 vs 16.0 μm in diameter, and extended 2–3 slender smooth processes. SCGN might be one of significant markers to reconsider the delineations of the structures of the mouse, and presumably rat, brainstem.
       
  • Real-time imaging of synaptic vesicle exocytosis by total internal
           reflection fluorescence (TIRF) microscopy
    • Abstract: Publication date: Available online 2 February 2018Source: Neuroscience ResearchAuthor(s): Mitsuharu MidorikawaAbstractSynaptic vesicles are one of the smallest organelle in the cell with their sizes far below the diffraction limit of the light microscopy. Exocytosis at the synapse is tightly regulated reaction which typically occurs within a millisecond after the arrival of an action potential. It has been assumed that synaptic vesicles have to be ready for immediate exocytosis upon the arrival of final trigger before exocytosis. But direct observation of the pre-exocytotic synaptic vesicle dynamics have been lacking. Total internal reflection microscopy (TIRFM) is a fluorescence microscopy which has best z-axis resolution (∼100 nm) as a light microscopy, and is close to that of the ultrathin section used for electron microscopy. Although its application is limited to the objects just beneath the plasma membrane, TIRFM has revealed dynamics of various organelles and proteins. We recently managed to dissociate mammalian neuronal presynaptic terminals and let the exocytotic sites adhere tightly to the coverslip. There, TIRFM revealed the detailed dynamics of pre-exocytotic vesicles. Our work opened up the way to visualize dynamics of sub-diffraction limited sized organelle in a real time, and will be useful for direct visualization of various synaptic components in the future.
       
  • U1 small nuclear RNA overexpression implicates autophagic-lysosomal system
           associated with AD
    • Abstract: Publication date: Available online 1 February 2018Source: Neuroscience ResearchAuthor(s): Zhi Cheng, Zhanqiang Du, Baohui Zhai, Zhuo Yang, Tao ZhangAbstractRecently, we reported that presenilin 1 considerably increased the expression level of U1 small nuclear RNA (snRNA) accompanied with the adverse change of amyloid precursor protein (APP) expression, β-amyloid (Aβ) production and cell apoptosis. In the present study, it was found that U1 snRNA overexpression significantly elevated the expression level of autophagy. Moreover, rapamycin further enhanced the Aβ production and cell apoptosis, whereas these processes were effectively inhibited by 3-MA. Acridine orange staining images showed that U1 snRNA overexpression not only activated autophagy pathway, but also led to the autophagic-lysosomal system dysfunction in cells. Immunofluorescence assay showed autophagic vacuoles localization with APP, which was the precursor protein of main component of toxic protein in AD. Meanwhile, the superoxide dismutase activity was remarkably decreased and MDA level was significantly increased by U1 snRNA overexpression in cells, suggesting that there was a possible pathway to elucidate how the U1 snRNA overexpression induced cell damage. We further found that U1 snRNA overexpression altered lysosomal biogenesis and autophagic-lysosomal fusion. In combination with our previous results, it suggests that the malfunction of autophagy pathway provides important insight into molecular mechanisms of augment the aggregation of Aβ and induction of cell apoptosis contributed to AD.
       
  • Stimulation-induced changes in diffusion and structure of calmodulin and
           calmodulin-dependent protein kinase II proteins in neurons
    • Abstract: Publication date: Available online 1 February 2018Source: Neuroscience ResearchAuthor(s): Morteza Heidarinejad, Hideki Nakamura, Takafumi InoueAbstractCalcium/calmodulin-dependent protein kinase II (CaMKII) and calmodulin (CaM) play essential roles in synaptic plasticity, which is an elementary process of learning and memory. In this study, fluorescence correlation spectroscopy (FCS) revealed diffusion properties of CaM, CaMKIIα and CaMKIIβ proteins in human embryonic kidney 293 (HEK293) cells and hippocampal neurons. A simultaneous multiple-point FCS recording system was developed on a random-access two-photon microscope, which facilitated efficient analysis of molecular dynamics in neuronal compartments. The diffusion of CaM in neurons was slower than that in HEK293 cells at rest, while the diffusion in stimulated neurons was accelerated and indistinguishable from that in HEK293 cells. This implied that activity-dependent binding partners of CaM exist in neurons, which slow down the diffusion at rest. Diffusion properties of CaMKIIα and β proteins implied that major populations of these proteins exist as holoenzymatic forms. Upon stimulation of neurons, the diffusion of CaMKIIα and β proteins became faster with reduced particle brightness, indicating drastic structural changes of the proteins such as dismissal from holoenzyme structure and further fragmentation.
       
  • Comparative review of adult midbrain and striatum neurogenesis with
           classical neurogenesis
    • Abstract: Publication date: Available online 12 January 2018Source: Neuroscience ResearchAuthor(s): Parisa FarzanehfarAbstractParkinson’s Disease (PD) motor symptoms are caused by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine cell replacement therapy (DA CRT), either by cell transplantation or endogenous repair, has been a potential treatment to replace dead cells and improve PD motor symptoms. Adult midbrain and striatum have been studied for many years to find evidence of neurogenesis. Although the literature is controversial, recent research has revived the possibility of neurogenesis here. This paper aims to review the process of neurogenesis (by focusing on gene expression patterns) in the adult midbrain/striatum and compare it with classical neurogenesis that occurs in developing midbrain, Sub Ventricular Zone (SVZ) and Sub Granular Zone (SGZ) of the adult brain.
       
  • Development of stereotaxic recording system for awake marmosets
           (Callithrix jacchus)
    • Abstract: Publication date: Available online 6 January 2018Source: Neuroscience ResearchAuthor(s): Masahiro Wakabayashi, Daisuke Koketsu, Hideki Kondo, Shigeki Sato, Kiichi Ohara, Zlata Polyakova, Satomi Chiken, Nobuhiko Hatanaka, Atsushi NambuAbstractThe common marmoset has been proposed as a potential alternative to macaque monkey as a primate model for neuroscience and medical research. Here, we have newly developed a stereotaxic neuronal recording system for awake marmosets under the head-fixed condition by modifying that for macaque monkeys. Using this system, we recorded neuronal activity in the cerebral cortex of awake marmosets and successfully identified the primary motor cortex by intracortical microstimulation. Neuronal activities of deep brain structures, such as the basal ganglia, thalamus, and cerebellum, in awake marmosets were also successfully recorded referring to magnetic resonance images. Our system is suitable for functional mapping of the brain, since the large recording chamber allows access to arbitrary regions over almost the entire brain, and the recording electrode can be easily moved stereotaxically from one site to another. In addition, our system is desirable for neuronal recording during task performance to assess motor skills and cognitive function, as the marmoset sits in the marmoset chair and can freely use its hands. Moreover, our system can be used in combination with cutting-edge techniques, such as two-photon imaging and optogenetic manipulation. This recording system will contribute to boosting neuroscience and medical research using marmosets.
       
 
 
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