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Current Opinion in Pharmacology
Journal Prestige (SJR): 2.504
Citation Impact (citeScore): 5
Number of Followers: 10  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1471-4892 - ISSN (Online) 1471-4973
Published by Elsevier Homepage  [3206 journals]
  • Adult hippocampal neurogenesis and antidepressants effects
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Barbara Planchez, Alexandre Surget, Catherine BelzungThe hippocampus is particularly involved in cognitive processes and is a key regulator of stress responses and emotions. Therefore, the role of adult-born neurons in this region has become a crucial field of research in order to understand mood and stress disorders, such as major depression. Many studies have characterized the role of these neurons in cognition, mood regulation and antidepressant actions. Nevertheless, the precise mechanisms underpinning these antidepressant effects remain unclear. In this review, we first discuss the effects of stress and antidepressant treatments on adult-born neurons, and subsequently, the role and mechanisms of neurogenesis in antidepressant action. Some studies have shown that adult-born neurons could affect overall hippocampal activity, thus normalizing the latter which could restore neuronal pathways underlying antidepressant effects.
       
  • Potential of glucocorticoids to treat intestinal inflammation during
           sepsis
    • Abstract: Publication date: August 2020Source: Current Opinion in Pharmacology, Volume 53Author(s): Kelly Van Looveren, Charlotte Wallaeys, Claude LibertGlucocorticoids (GCs) are steroid hormones characterized by their anti-inflammatory and immunosuppressive nature. Although GCs are very commonly prescribed, in several diseases, including sepsis, their clinical treatment is hampered by side effects and by the occurrence of glucocorticoid resistance (GCR). Sepsis is defined as a life-threatening organ dysfunction, initiated by a dysregulated systemic host response to infections. With at least 19 million cases per year and a lethality rate of about 25%, sepsis is one of the most urgent unmet medical needs. The gut is critically affected during sepsis and is considered as a driving force in this disease. Despite there is no effective treatment for sepsis, pre-clinical studies show promising results by preserving or restoring gut integrity. Since GC treatment reveals therapeutic effects in Crohn’s disease (CD) and in pre-clinical sepsis models, we hypothesize that targeting GCs to the gut or stimulating local GC production in the gut forms an interesting strategy for sepsis treatment. According to recent findings that show that dimerization of the glucocorticoid receptor (GR) is essential in inducing anti-inflammatory effects in pre-clinical sepsis models, we predict that new generation GCs that selectively dimerize the GR, can therefore positively affect the outcome of sepsis treatment.
       
  • Next-generation drug repurposing using human genetics and network biology
    • Abstract: Publication date: Available online 22 January 2020Source: Current Opinion in PharmacologyAuthor(s): Serguei Nabirotchkin, Alex E Peluffo, Philippe Rinaudo, Jinchao Yu, Rodolphe Hajj, Daniel CohenDrug repurposing has attracted increased attention, especially in the context of drug discovery rates that remain too low despite a recent wave of approvals for biological therapeutics (e.g. gene therapy). These new biological entities-based treatments have high costs that are difficult to justify for small markets that include rare diseases. Drug repurposing, involving the identification of single or combinations of existing drugs based on human genetics data and network biology approaches represents a next-generation approach that has the potential to increase the speed of drug discovery at a lower cost. This Pharmacological Perspective reviews progress and perspectives in combining human genetics, especially genome-wide association studies, with network biology to drive drug repurposing for rare and common diseases with monogenic or polygenic etiologies. Also, highlighted here are important features of this next generation approach to drug repurposing, which can be combined with machine learning methods to meet the challenges of personalized medicine.
       
  • Null hypothesis significance testing and effect sizes: can we ‘effect’
           everything … or … anything'
    • Abstract: Publication date: Available online 14 January 2020Source: Current Opinion in PharmacologyAuthor(s): David P LovellThe Null Hypothesis Significance Testing (NHST) paradigm is increasingly criticized. Estimation approaches such as point estimates and confidence intervals, while having limitations, provide better descriptions of results than P-values and statements about significance levels. Their use is supported by many statisticians. The effect size approach is an important part of power and sample size calculations at the experimental design stage and in meta-analysis and in the interpretation of the biological importance of study results. Care is needed, however, to ensure that such effect sizes are relevant for the endpoint. Effect sizes should not be used to interpret results without accompanying limits, such as confidence intervals. New methods, especially Bayesian approaches, are being developed; however, no single method provides a simple answer. Rather there is a need to improve researchers understanding of the complex issues underlying experimental design, statistical analysis and interpretation of results.
       
  • Impact of gut microbiota on neurogenesis and neurological diseases during
           infancy
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Tomás Cerdó, Estefanía Diéguez, Cristina CampoyThe first years of life constitute a crucial period for neurodevelopment and a window of opportunity to develop new strategies to prevent neurological and mental diseases. Different studies have shown the influence of gut bacteria in neurogenesis and a functional relationship between gut microbiota and the brain, known as ‘gut–brain axis’, in which the intestinal microbiota is proposed to play a key role in neurophysiological processes. It has been observed that certain microbiome metabolites could be related to the development of neurological disorders through mechanisms still unknown. Then, more studies are needed to broaden the knowledge regarding the relationship between the Central Nervous System and the gastrointestinal tract, which could help to develop new preventive and treatment protocols.
       
  • Ependymal cells in the spinal cord as neuronal progenitors
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Victoria Moreno-ManzanoEpendymal cells are neural progenitors and form part of the central canal of the spinal cord. Therefore, ependymal cells could serve as a potential source of neural progenitors for regenerative medicine applications. Such applications consist of endogenous activation or exogenous transplantation, alone or in combination with pharmacological treatments, to repair spinal cord injuries. This mini review describes the main phenotypical characteristics of ependymal cells from spinal cord and the opportunities offered for spinal cord injury therapeutic application.
       
  • Understanding the effects of air pollution on neurogenesis and gliogenesis
           in the growing and adult brain
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Enrica Boda, Antonello E Rigamonti, Valentina BollatiExposure to air pollution — and particularly to particulate matter (PM) – is strongly associated with higher risk of neurodevelopmental disorders, poor mental health and cognitive defects. In animal models, disruption of CNS development and disturbances of adult neurogenesis contribute to PM neurotoxicity. Recent studies show that gestational PM exposure not only affects embryonic neurodevelopment, but also disturbs postnatal brain growth and maturation, by interfering with neurogenic/gliogenic events, myelination and synaptogenesis. Similarly, adult neurogenesis is affected at many levels, from neural stem cell amplification up to the maturation and integration of novel neurons in the adult brain parenchyma. The underlying mechanisms are still by and large unknown. Beyond microglia activation and neuroinflammation, recent studies propose a role for novel epigenetic mechanisms, including DNA methylation and extracellular vesicles-associated microRNAs.
       
  • NG2 cells and their neurogenic potential
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Denisa Kirdajova, Miroslava AnderovaNG2 cells, which comprise a cycling population of glial cells, appear in the early phases of development and are present in the adult central nervous system. When a specific subpopulation of NG2 cells give rise to myelinating oligodendrocytes, they are also termed as oligodendrocyte precursor cells. Considering their capacity to proliferate and differentiate into other cellular types, their fate has been extensively investigated in several genetically modified mice. It is generally accepted that NG2 cells are restricted to the oligodendrocyte lineage, but numerous reports describe their differentiation into astrocytes or even neurons. Here, we summarize studies that can prove and also disprove possible neurogenesis from NG2 cells in the different regions of the brain and spinal cord, with the main emphasis on the developmental stages and pathological conditions.Graphical abstractGraphical abstract for this article
       
  • Nutrients and neurogenesis: the emerging role of autophagy and gut
           microbiota
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Virve Cavallucci, Marco Fidaleo, Giovambattista PaniAdult neurogenesis, the generation of mature functional neurons from neural stem cells in specific regions of the adult mammalian brain, is implicated in brain physiology, neurodegeneration and mood disorders. Among the many intrinsic and extrinsic factors that modulate neurogenic activity, the role of nutrients, energy metabolism, and gut microbiota has recently emerged. It is increasingly evident that excessive calorie intake accelerates the age-dependent decline of neurogenesis, while calorie restriction and physical exercise have the opposite effect. Mechanistically, nutrient availability could affect neurogenesis by modulating autophagy, a cell-rejuvenating process, in neural stem cells. In parallel, diet can alter the composition of gut microbiota thus impacting the intestine-neurogenic niche communication. These exciting breakthroughs are here concisely reviewed.
       
  • New insights into the regulatory roles of microRNAs in adult neurogenesis
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Marta Esteves, Catarina Serra-Almeida, Cláudia Saraiva, Liliana BernardinoAdult neurogenesis, the process of generation of new functional neurons from neural stem cells, occurs in the subventricular zone and the subgranular zone neurogenic niches. This neurogenic process is tightly controlled by several intrinsic factors, including microRNAs (miRNAs), a class of small non-coding RNAs, which control protein translation. MiRNAs have emerged as important regulators of both embryonic and adult neural stem cells self-renewal and proliferation, neuronal differentiation, migration, maturation and integration into the complex neuronal circuitry. Herein, we will provide a review of the most prominent and recent findings underlying the physiological regulatory role of several miRNAs during adult neurogenesis.Graphical abstractGraphical abstract for this article
       
  • Untangling human neurogenesis to understand and counteract brain disorders
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Ruth Beckervordersandforth, Chiara RolandoNeurogenesis in the human postnatal brain occurs in two regions, the subventricular zone of the later ventricle and the dentate gyrus of the hippocampus. While it is well accepted that SVZ and hippocampal neurogenesis are active during juvenile stages in human, their contribution during adulthood and ageing as well as pathological states is recently animating the neural stem cell research field. In this review we will discuss recent evidence about the organization of SVZ and hippocampal neurogenic niches, and will report on how human adult neurogenesis may contribute to disease and appears to respond to neurodegeneration. In light of these novel findings, we will discuss how we can target human adult neurogenesis in order to influence brain disease trajectories.
       
  • Endocannabinoid system and adult neurogenesis: a focused review
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Sergio Oddi, Lucia Scipioni, Mauro MaccarroneThe endocannabinoid system (eCB) is a ubiquitous lipid signaling system composed of at least two receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. Within the brain, the eCB system is highly expressed in the hippocampus and controls basic biological processes, including neuronal proliferation, migration and differentiation, which are intimately linked with embryonal neurogenesis. Accumulated preclinical evidence has indicated that eCBs play a major role also in regulating adult neurogenesis. Increased cannabinoid receptor activity, either by increased eCB content or by pharmacological blockade of their degradation, produces neurogenic effects alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. Therefore, in the light of the higher therapeutic potential of adult neurogenesis compared to the embryonic one, here we sought to summarize the most recent evidence pointing towards a neurogenic role for eCBs in the adult brain, both under normal and pathological conditions.
       
  • Histone deacetylases 1, 2 and 3 in nervous system development
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Santosh R D’MelloAlthough histone acetylases (HDACS) were initially believed to render chromatin in a transcriptionally repressed state by deacetylating histones, it is now known that they both repress and activate transcription. Moreover, HDACs regulate the activity and/or function of a large number of other cellular proteins localized in the nucleus and cytoplasm. Accumulating evidence indicates that HDACs also play a key role in the development of the nervous system. This review focuses on three classical HDACS — HDACs 1, 2 and 3. Although much evidence on the involvement of HDACs in neurodevelopment has come from the use of pharmacological inhibitors, because these agents are not specific in their action on individual HDAC proteins, this review only describes evidence derived from the use of molecular genetic approaches. Our review describes that HDACs 1, 2 and 3 play crucial roles in neurodevelopment by regulating neurogenesis, gliogenesis, the development of neural circuitry and synaptic transmission.
       
  • Editorial
    • Abstract: Publication date: Available online 10 December 2019Source: Current Opinion in PharmacologyAuthor(s): Michael Williams, David Trist
       
  • Adult hippocampal neurogenesis and antidepressants effects
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Barbara Planchez, Alexandre Surget, Catherine BelzungThe hippocampus is particularly involved in cognitive processes and is a key regulator of stress responses and emotions. Therefore, the role of adult-born neurons in this region has become a crucial field of research in order to understand mood and stress disorders, such as major depression. Many studies have characterized the role of these neurons in cognition, mood regulation and antidepressant actions. Nevertheless, the precise mechanisms underpinning their antidepressant effects remain unclear. In this review, we first discuss the effects of stress and antidepressant treatments on adult neurogenesis, and subsequently, the functional roles of adult-born neurons and the mechanisms underlying their antidepressant action. Some studies have shown that adult-born neurons could affect overall hippocampal activity and thus normalize it under depression, which could restore neuronal pathways underlying antidepressant effects.
       
  • Neuroimmune and epigenetic mechanisms underlying persistent loss of
           hippocampal neurogenesis following adolescent intermittent ethanol
           exposure
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Victoria Macht, Fulton T Crews, Ryan P VetrenoAlcohol abuse and binge drinking are common during adolescence — a maturational period characterized by heightened hippocampal neuroplasticity and neurogenesis. Preclinical rodent models of adolescent binge drinking (i.e., adolescent intermittent ethanol [AIE]) find unique vulnerability of adolescent hippocampal neurogenesis with reductions persisting into adulthood after ethanol cessation. Recent discoveries implicate increased neuroimmune signaling and decreased neurotrophic support through epigenetic mechanisms in the persistent AIE-induced loss of neurogenesis. Importantly, interventions aimed at rectifying the increased neuroimmune signaling and neurotrophic-epigenetic modifications through physical activity, anti-inflammatory drugs, and histone deacetylase inhibitors protect and recover the loss of neurogenesis and cognitive deficits. The mechanisms underlying the persistent AIE-induced loss of adult hippocampal neurogenesis could contribute to broader neurodegeneration, loss of hippocampal neuroplasticity, and cognitive dysfunction.
       
  • Rejuvenating subventricular zone neurogenesis in the aging brain
    • Abstract: Publication date: February 2020Source: Current Opinion in Pharmacology, Volume 50Author(s): Ronald R Cutler, Erzsebet KokovayNeural stem cells exist in specialized regions of the brain and have the capacity to give rise to neurons and glia over the lifespan. The process of giving rise to new neurons, also known as neurogenesis, is thought to be important in cognition and certain types of brain repair. However, during aging, neural stem cell number and function is reduced resulting in fewer new neurons and declines in learning, memory and repair. Recently, research has approached this problem through the lens of rejuvenation that now has produced several strategies, from dietary to pharmacological interventions, to restore functional neurogenesis that resembles the youthful brain. Here, we outline aging in the subventricular zone neurogenic niche, review the multiple modalities of rejuvenation strategies, and propose next steps for future studies to approach translational outcomes.
       
  • Adult hippocampal neurogenesis as a target for cocaine addiction: a review
           of recent developments
    • Abstract: Publication date: Available online 8 November 2019Source: Current Opinion in PharmacologyAuthor(s): Estela Castilla-Ortega, Luis J SantínBasic research in rodents has shown that adult hippocampal neurogenesis (AHN) plays a key role in neuropsychiatric disorders that compromise hippocampal functioning. The discovery that dependence-inducing drugs regulate AHN has led to escalating interest in the potential involvement of AHN in drug addiction over the last decade, with cocaine being one of the most frequently investigated drugs. This review argues that, unlike other drugs of abuse, preclinical studies do not, overall, support that cocaine induces a marked or persistent impairment in AHN. Nevertheless, experimental reduction of AHN consistently exacerbates vulnerability to cocaine. Interestingly, preliminary evidence suggests that, on the contrary, increasing AHN might help both to prevent and treat addiction.Graphical abstractGraphical abstract for this article
       
 
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