Journal Cover Journal of Neural Transmission
  [SJR: 1.034]   [H-I: 86]   [2 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0300-9564 - ISSN (Online) 1435-1463
   Published by Springer-Verlag Homepage  [2350 journals]
  • Neuroinflammation in neurodegeneration: role in pathophysiology,
           therapeutic opportunities and clinical perspectives
    • Authors: Guillaume Dorothée
      Pages: 749 - 750
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-018-1880-6
      Issue No: Vol. 125, No. 5 (2018)
       
  • Let’s make microglia great again in neurodegenerative disorders
    • Authors: Marie-Victoire Guillot-Sestier; Terrence Town
      Pages: 751 - 770
      Abstract: All of the common neurodegenerative disorders—Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and prion diseases—are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids. Microglial phagocytosis is compromised early in the disease process, obfuscating clearance of abnormal proteins. This review identifies immune pathologies shared by the major neurodegenerative disorders. The overarching concept is that aberrant innate immune pathways can be targeted for return to homeostasis in hopes of coaxing microglia into clearing neurotoxic misfolded proteins.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1792-x
      Issue No: Vol. 125, No. 5 (2018)
       
  • Neuroinflammatory responses in Alzheimer’s disease
    • Authors: Cira Dansokho; Michael Thomas Heneka
      Pages: 771 - 779
      Abstract: Neuroinflammatory responses in Alzheimer’s disease (AD) are complex and not fully understood. They involve various cellular and molecular players and associate interaction between the central nervous system (CNS) and the periphery. Amyloid peptides within the senile plaques and abnormally phosphorylated tau in neurofibrillary tangles are able to initiate inflammatory responses, in brain of AD patients and in mouse models of this disease. The outcome of these responses on the pathophysiology of AD depends on several factors and can be either beneficial or detrimental. Thus, understanding the role of neuroinflammation in AD could help to develop safer and more efficient therapeutic strategies. This review discusses recent knowledge on microglia responses toward amyloid and tau pathology in AD, focusing on the role of Toll-like receptors and NOD-like receptor protein 3 (NLRP3) inflammasome activation in microglial cells.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1831-7
      Issue No: Vol. 125, No. 5 (2018)
       
  • The IL-1β phenomena in neuroinflammatory diseases
    • Authors: Andrew S. Mendiola; Astrid E. Cardona
      Pages: 781 - 795
      Abstract: It is becoming increasingly clear that neuroinflammation has a causal role in the pathogenesis of central nervous system (CNS)-related diseases, and therefore therapeutic strategies targeting the regulation or availability of inflammatory mediators can be used to prevent or mitigate pathology. Interestingly, the proinflammatory cytokine, interleukin-1 beta (IL-1β), has been implicated in perpetuating immune responses and contributing to disease severity in a variety of CNS diseases ranging from multiple sclerosis, neurodegenerative diseases, traumatic brain injury, and diabetic retinopathy. Moreover, pharmacological blockade of IL-1 signaling has shown to be beneficial in some autoimmune and autoinflammatory diseases, making IL-1β a promising therapeutic target in neuroinflammatory conditions. This review highlights recent advances of our understanding on the multifaceted roles of IL-1β in neuroinflammatory diseases.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1732-9
      Issue No: Vol. 125, No. 5 (2018)
       
  • Type-I interferon pathway in neuroinflammation and neurodegeneration:
           focus on Alzheimer’s disease
    • Authors: Juliet M. Taylor; Zachery Moore; Myles R. Minter; Peter J. Crack
      Pages: 797 - 807
      Abstract: Past research in Alzheimer’s disease (AD) has largely been driven by the amyloid hypothesis; the accompanying neuroinflammation seen in AD has been assumed to be consequential and not disease modifying or causative. However, recent data from both clinical and preclinical studies have established that the immune-driven neuroinflammation contributes to AD pathology. Key evidence for the involvement of neuroinflammation in AD includes enhanced microglial and astroglial activation in the brains of AD patients, increased pro-inflammatory cytokine burden in AD brains, and epidemiological evidence that chronic non-steroidal anti-inflammatory drug use prior to disease onset leads to a lower incidence of AD. Identifying critical mediators controlling this neuroinflammation will prove beneficial in developing anti-inflammatory therapies for the treatment of AD. The type-I interferons (IFNs) are pleiotropic cytokines that control pro-inflammatory cytokine secretion and are master regulators of the innate immune response that impact on disorders of the central nervous system. This review provides evidence that the type-I IFNs play a critical role in the exacerbation of neuroinflammation and actively contribute to the progression of AD.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1745-4
      Issue No: Vol. 125, No. 5 (2018)
       
  • Differential contribution of microglia and monocytes in neurodegenerative
           diseases
    • Authors: Caroline Baufeld; Elaine O’Loughlin; Narghes Calcagno; Charlotte Madore; Oleg Butovsky
      Pages: 809 - 826
      Abstract: Neuroinflammation is a hallmark of neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Microglia, the innate immune cells of the CNS, are the first to react to pathological insults. However, multiple studies have also demonstrated an involvement of peripheral monocytes in several neurodegenerative diseases. Due to the different origins of these two cell types, it is important to distinguish their role and function in the development and progression of these diseases. In this review, we will summarize and discuss the current knowledge of the differential contributions of microglia and monocytes in the common neurodegenerative diseases AD, PD, and ALS, as well as multiple sclerosis, which is now regarded as a combination of inflammatory processes and neurodegeneration. Until recently, it has been challenging to differentiate microglia from monocytes, as there were no specific markers. Therefore, the recent identification of specific molecular signatures of both cell types will help to advance our understanding of their differential contribution in neurodegenerative diseases.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1795-7
      Issue No: Vol. 125, No. 5 (2018)
       
  • Innate immunity in Alzheimer’s disease: the relevance of animal
           models'
    • Authors: Diana K. Franco Bocanegra; James A. R. Nicoll; Delphine Boche
      Pages: 827 - 846
      Abstract: The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment. With respect to Alzheimer’s disease (AD), much of the experimental information currently known about this disease has been gathered from studies using mainly mice as models. Therefore, it is notably important to fully characterise the differences between mice and humans regarding important aspects of the disease. It is now widely known that inflammation plays an important role in the development of AD, a role that is not only a response to the surrounding pathological environment, but rather seems to be strongly implicated in the aetiology of the disease as indicated by the genetic studies. This review highlights relevant differences in inflammation and in microglia, the innate immune cell of the brain, between mice and humans regarding genetics and morphology in normal ageing, and the relationship of microglia with AD-like pathology, the inflammatory profile, and cognition. We conclude that some noteworthy differences exist between mice and humans regarding microglial characteristics, in distribution, gene expression, and states of activation. This may have repercussions in the way that transgenic mice respond to, and influence, the AD-like pathology. However, despite these differences, human and mouse microglia also show similarities in morphology and behaviour, such that the mouse is a suitable model for studying the role of microglia, as long as these differences are taken into consideration when delineating new strategies to approach the study of neurodegenerative diseases.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1729-4
      Issue No: Vol. 125, No. 5 (2018)
       
  • In vivo PET imaging of neuroinflammation in Alzheimer’s disease
    • Authors: Julien Lagarde; Marie Sarazin; Michel Bottlaender
      Pages: 847 - 867
      Abstract: Increasing evidence suggests that neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer’s disease (AD). Molecular imaging by PET may be a useful tool to assess neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia. In the present review, we describe the most widely used PET tracers targeting the TSPO, the methodological issues in tracer quantification and summarize the results obtained by TSPO PET imaging in AD, as well as in neurodegenerative disorders associated with AD, in psychiatric disorders and ageing. We also briefly describe alternative PET targets and imaging modalities to study neuroinflammation. Lastly, we question the meaning of PET imaging data in the context of a highly complex and multifaceted role of neuroinflammation in neurodegenerative diseases. This overview leads to the conclusion that PET imaging of neuroinflammation is a promising way of deciphering the enigma of the pathophysiology of AD and of monitoring the effect of new therapies.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-017-1731-x
      Issue No: Vol. 125, No. 5 (2018)
       
  • Kynurenine is correlated with IL-1β in plasma of schizophrenia
           patients
    • Authors: Helena P. G. Joaquim; Alana C. Costa; Wagner F. Gattaz; Leda Leme Talib
      Pages: 869 - 873
      Abstract: The etiology of schizophrenia is still unclear. It is well-known that pro-inflammatory cytokines are higher in schizophrenia patients since the first episode psychosis comparing to healthy controls. Inflammatory downstream cascades influence different cellular pathways, like the displacement of the tryptophan (TRP) metabolism to the production of kynurenine (KYN) instead of serotonin, which results in the generation of several neuro and immunoactive metabolites. The aim of this study was to determine TRP, KYN and IL-1β plasma levels in first-onset schizophrenia (n = 28) and healthy controls (n = 30). The plasmatic levels of TRP and KYN were decreased in schizophrenic patients (p = 0.004 and p = 0.002, respectively), but there was no difference in the ratio of KYN/TRP (p = 0.554) or either in IL-1β (p = 0.101). Positive correlation was observed between KYN and IL-1β only in the schizophrenia group (r = 0.461, p = 0.021). And, there was also positive correlation between KYN and Positive and Negative Symptoms Scale (PANSS) (r = 0.395, p = 0.037). There is no correlation between the other analytes and other parameters of PANSS. Although our results of KYN have been different than expected and there was no difference in the KYN/TRP ratio, we observed a positive correlation between IL-1β and KYN, corroborating findings that pro-inflammatory agents hold up the KYN pathway.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-018-1838-8
      Issue No: Vol. 125, No. 5 (2018)
       
  • Interleukin 6 and complement serum level study in Parkinson’s
           disease
    • Authors: Branislav Veselý; Michal Dufek; Vojtech Thon; Miroslav Brozman; Silvia Királová; Tatiana Halászová; Eva Koriťáková; Ivan Rektor
      Pages: 875 - 881
      Abstract: The objective of this study is to assess whether elevation of serum inflammatory markers levels may indicate the progression of clinical impairment in Parkinson’s disease (PD) patients. In 47 PD patients, the serum levels of the C3 and C4 part of the complement and Interleukin-6 (IL-6) were measured. The results at baseline and after 2 years were correlated with scales measuring memory, depression, motor symptoms, and quality of life. Patients with higher levels of C3 and C4 at baseline had decreased quality of life, verbal ability, and memory. Patients with higher IL-6 at baseline showed worse depression scores at 2 years. Patients with persistently higher levels of C3 and C4 at 2 years had worse quality of life and memory ability. Uncorrected p values are reported due to the exploratory nature of the study. The results indicate an impact of inflammation on non-motor signs and quality of life in PD. The increase of levels of serum inflammatory biomarkers may indicate the progression of non-motor impairment in PD.
      PubDate: 2018-05-01
      DOI: 10.1007/s00702-018-1857-5
      Issue No: Vol. 125, No. 5 (2018)
       
  • Pupillometry as an indicator of l -DOPA dosages in Parkinson’s
           disease patients
    • Authors: O. Bartošová; C. Bonnet; O. Ulmanová; M. Šíma; F. Perlík; E. Růžička; O. Slanař
      Pages: 699 - 703
      Abstract: Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of l-DOPA and dopamine. The aim of this study is to evaluate the effect of l-DOPA dosage on pupillometric parameters in Parkinson’s disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose–response relationship was found between the maximum pupil diameter and both the morning l-DOPA dose (R 2 = 0.78) and the total daily l-DOPA dose (R 2 = 0.93). A sigmoid-shaped curve best describes the dose–response relationship, with a ceiling effect at about 400 mg l-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of l-DOPA, especially with daily doses below 400 mg l-DOPA.
      PubDate: 2018-04-01
      DOI: 10.1007/s00702-017-1829-1
      Issue No: Vol. 125, No. 4 (2018)
       
  • Decreased plasma agmatine levels in autistic subjects
    • Authors: Erman Esnafoglu; İlhan İrende
      Pages: 735 - 740
      Abstract: Agmatine is a polyamine endogenously synthesized from arginine and is considered to be a new neurotransmitter. Agmatine has been implicated in the pathophysiology of several diseases such as anxiety disorder, depression, and schizophrenia. Agmatine also possesses anticonvulsant, neuroprotective, antiapoptotic, antioxidant, anxiolytic, and antidepressant effects. Furthermore, agmatine inhibits the nitric oxide synthase enzyme and exerts antagonist effects on NMDA, alpha-2, and imidazoline receptors. Considering these characteristics, the present study investigated whether agmatine plays a role in the pathogenesis of autistic spectrum disorders (ASDs). Therefore, plasma agmatine levels were evaluated in 34 patients with ASD and 28 non-ASD controls. Plasma agmatine levels were measured using the HPLC method. The study found remarkably lower agmatine levels in patients with ASD compared with the non-ASD control group (p < 0.001). These findings support the notion that agmatine might contribute to the pathogenesis of ASD and may serve as a new target for treatment.
      PubDate: 2018-04-01
      DOI: 10.1007/s00702-017-1836-2
      Issue No: Vol. 125, No. 4 (2018)
       
  • CHRFAM7A gene expression in schizophrenia: clinical correlates and the
           effect of antipsychotic treatment
    • Authors: Sunil V. Kalmady; Rimjhim Agrawal; Deepthi Venugopal; Venkataram Shivakumar; Anekal C. Amaresha; Sri Mahavir Agarwal; Manjula Subbanna; Ashwini Rajasekaran; Janardhanan C. Narayanaswamy; Monojit Debnath; Ganesan Venkatasubramanian
      Pages: 741 - 748
      Abstract: Earlier studies have implicated CHRNA7, coding α-7 nicotinic acetylcholine receptor (α7 nAChR), and its partially duplicated chimeric gene CHRFAM7A in schizophrenia. However, the relationship between the alterations in peripheral gene expression of CHRFAM7A and severity of clinical symptoms has not been examined. Furthermore, potential influence of the antipsychotic medication on CHRFAM7A expression in drug-naive or drug-free schizophrenia is an unexplored area. CHRFAM7A gene expression in lymphocytes was analyzed in 90 antipsychotic-naïve or free schizophrenia patients using TaqMan-based quantitative RT-PCR. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms (SANS). The relationship between psychopathology and CHRFAM7A expression was examined. In addition, measurement of CHRFAM7A gene expression was repeated during follow-up after short-term antipsychotic treatment in 38 patients. There was significant inverse correlation between CHRFAM7A expression and total negative psychopathology score—SANS, and this relationship persisted after accounting for possible confounders such as age, sex and smoking. On exploration of the factor structure of psychopathology using principal component analysis, all the negative symptoms—affective flattening, alogia, apathy, anhedonia and inattention were found to be inversely associated with CHRFAM7A expression. Furthermore, analysis of repeated measures revealed a significant increase in CHRFAM7A expression in patients after short-term administration of antipsychotic medication. Our study observations support the role for CHRFAM7A gene in schizophrenia pathogenesis and suggest a potential novel link between deficient CHRFAM7A expression and negative psychopathology. Furthermore, up-regulation of CHRFAM7A gene expression by antipsychotics suggests that it could be a potential state marker for clinical severity.
      PubDate: 2018-04-01
      DOI: 10.1007/s00702-017-1833-5
      Issue No: Vol. 125, No. 4 (2018)
       
  • On the neuronal circuitry mediating l -DOPA-induced dyskinesia
    • Authors: M. Angela Cenci; Henrik Jörntell; Per Petersson
      Abstract: With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.
      PubDate: 2018-04-27
      DOI: 10.1007/s00702-018-1886-0
       
  • Cerebrovascular inflammation is associated with tau pathology in Guam
           parkinsonism dementia
    • Authors: Petra Majerova; Ralph M. Garruto; Andrej Kovac
      Abstract: Parkinsonism–dementia complex of Guam (Guam PDC) is a neurodegenerative disease with parkinsonism and early onset Alzheimer-like dementia. Guam PDC belongs to the family of neurodegenerative disorders, known as tauopathies, which are histopathologically characterized by abnormal deposition of microtubule-associated protein tau. While changes in the blood–brain barrier (BBB) in Alzheimer’s disease are increasingly recognized, dysfunction of BBB in Guam PDC has not been extensively studied. In this study, we characterized cerebrovascular changes in the patients with Guam PDC. The brain tissue from ten post-mortem Guam PDC patients and six non-demented controls were assessed for structural and functional changes in BBB. Entorhinal cortex sections were immunostained for the markers of brain endothelial cells (claudin-5, occludin, and collagen IV) and inflammation (VCAM-1, ICAM-1, P-Selectin, and E-Selectin). The ultrastructure of brain capillaries was investigated by confocal microscopy and morphological changes and intensity alterations were evaluated. We found a significant decrease of tight junction proteins and the upregulation of adhesion molecules that correlated with the presence of neurofibrillary tangles. In addition, we showed the presence of CD3+-positive cells in the brain areas affected by pathological lesions. Our findings indicate that pathological lesions in Guam PDC are associated with inflammatory changes of brain capillaries and could mediate transmigration of cells to the brain parenchyma.
      PubDate: 2018-04-26
      DOI: 10.1007/s00702-018-1883-3
       
  • Correction to: Pupillometry as an indicator of l -DOPA dosages in
           Parkinson’s disease patients
    • Authors: O. Bartošová; C. Bonnet; O. Ulmanová; M. Šíma; F. Perlík; E. Růžička; O. Slanař
      Abstract: Unfortunately, original article has been published without acknowledgement section.
      PubDate: 2018-04-11
      DOI: 10.1007/s00702-018-1884-2
       
  • COQ2 variants in Parkinson’s disease and multiple system atrophy
    • Authors: Michitaka Mikasa; Kazuaki Kanai; Yuanzhe Li; Hiroyo Yoshino; Kaoru Mogushi; Arisa Hayashida; Aya Ikeda; Sumihiro Kawajiri; Yasuyuki Okuma; Kenichi Kashihara; Tatsuya Sato; Hiroshi Kondo; Manabu Funayama; Kenya Nishioka; Nobutaka Hattori
      Abstract: Coenzyme Q2, polyprenyltransferase (COQ2) variants have been reported to be associated with multiple system atrophy (MSA). However, the relationship between COQ2 variants and familial Parkinson’s disease (PD) remains unclear. We investigated the frequency of COQ2 variants and clinical symptoms among familial PD and MSA. We screened COQ2 using the Sanger method in 123 patients with familial PD, 52 patients with sporadic PD, and 39 patients with clinically diagnosed MSA. Clinical information was collected from medical records for the patients with COQ2 variants. Allele frequencies of detected rare non-synonymous variants were compared by public database of the Exome Aggregation Consortium (ExAC) and Japanese genetic variation database, using Fisher’s exact test. We detected two probands with rare variants in COQ2, the p.P157S from Family A, whose patient was clinically diagnosed as having juvenile PD, and the p.H15 N/p.G331S from Family B, whose patients shared common symptoms of PD. Furthermore, in an association study comparing these familial PD and MSA cases with a public variant database, eight non synonymous variants were detected in COQ2. Three of these were very rare variants, namely, p.P157S, p.L261Qfs*4, and p.G331S, and one variant, p.G21S, was found to show a significant association with familial PD. COQ2 variants rarely may associate with the disease onset of familial PD. Our findings contribute to an understanding of COQ2 variants in neurodegenerative disorders.
      PubDate: 2018-04-11
      DOI: 10.1007/s00702-018-1885-1
       
  • 90 years of monoamine oxidase: some progress and some confusion
    • Authors: Keith F. Tipton
      Abstract: It would not be practical to attempt to deal with all the advances that have informed our understanding of the behavior and functions of this enzyme over the past 90 years. This account concentrates key advances that explain why the monoamine oxidases remain of pharmacological and biochemical interest and on some areas of continuing uncertainty. Some issues that remain to be understood or are in need of further clarification are highlighted.
      PubDate: 2018-04-10
      DOI: 10.1007/s00702-018-1881-5
       
  • Clinical utility of pharmacogenetic testing in children and adolescents
           with severe mental disorders
    • Authors: Hilario Blasco-Fontecilla
      Abstract: This is a retrospective cohort study of 20 children and adolescents to evaluate the clinical utility of a pharmacogenetic decision support tool. Twenty children and adolescents underwent pharmacogenetic testing between June 2014 and May 2017. All children and adolescents were evaluated at Puerta de Hierro University Hospital-Majadahonda (Madrid, Spain). We report the proportion of patients achieving clinical improvement, amelioration of side effects, and changes in number of drugs. Data normality was assessed with the Shapiro–Wilk test, and changes of pre- and post-pharmacogenetic testing were analyzed with the Wilcoxon test for paired samples. A two-sided p value threshold of 0.05 was considered for significance. Pharmacogenetic testing helped to improve the clinical outcome as measured by the Clinical Global Impressions (CGI) Scale in virtually all children (95%; 19 out of 20 children). The CGI improvement (CGI-I) was 2 (0.79) (range 1–4), 2.1 (0.56) (range 1–3), and 1.9 (0.99) (range 1–4) in foster and non-foster care children, respectively. Pharmacogenetic testing also helped to reduce the number of children using polypharmacy (from 65 to 45%), the mean number of drugs per children (from 3.3 to 2.4 drugs, p = 0.017), and self-reported relevant side effects (p = 0.006). Pharmacogenetic testing helped to improve the clinical outcome, and to reduce polypharmacy and the number of drugs used in children and adolescents with severe mental disorders. More evidence using robust (i.e., clinical trials) independent studies is required to properly determine the clinical utility and cost-effectiveness of pharmacogenetic testing tools in children and adolescents with mental disorders.
      PubDate: 2018-04-06
      DOI: 10.1007/s00702-018-1882-4
       
  • Behavioral mechanisms underlying the maternal disruptive effect of
           serotonin 5-HT 2A receptor activation in Sprague–Dawley rats
    • Authors: Ruiyong Wu; Collin Davis; Ming Li
      Abstract: Recent evidence indicates that acute activation of 5-HT2A receptors causes a disruption of maternal behavior in rats. However, the behavioral mechanisms underlying such a disruption are not known. We addressed this issue using two behavioral approaches targeting the maternal motivational and emotional processing systems. First, we used the pup-separation technique to increase maternal motivation to see whether pup separation is capable of reducing the maternal disruptive effect of TCB-2 (a high-affinity 5-HT2A agonist) treatment. On postpartum days 4 and 6, different groups of Sprague–Dawley dams were treated with the TCB-2 (5.0 mg/kg, sc) or vehicle and their maternal behaviors were tested after either a 4-h pup-separation or no-pup-separation condition. Although acute TCB-2 injection disrupted maternal behavior, this disruption was not attenuated by pup separation, even after we optimized the timing of separation to maximize its increase on maternal motivation. Acute TCB-2 also impaired the retrieval of food pellets, suggesting a general effect on motivated behaviors. Next, we used a pup preference test and found that dams treated with TCB-2 exhibited an even stronger preference to pups over a male conspecific than vehicle-treated dams, indicating an enhanced motivational and emotional processing of the rewarding property of pups. These findings suggest that TCB-2 has a disruptive effect on rat maternal behavior, and this disruption is not likely due to the drug’s effect on mothers’ motivational and emotional processing of the incentive salience of pups, although this motivational suppression account cannot be completely ruled out. Future work could explore other possible behavioral mechanisms, such as the drug’s effect on executive function.
      PubDate: 2018-04-03
      DOI: 10.1007/s00702-018-1878-0
       
 
 
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