scholarly journals Cannabinoid signalling in embryonic and adult neurogenesis: possible implications for psychiatric and neurological disorders

2018 ◽  
Vol 31 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Rúbia W. de Oliveira ◽  
Cilene L. Oliveira ◽  
Francisco S. Guimarães ◽  
Alline C. Campos
Keyword(s):  
Animal Models ◽  
Adult Neurogenesis ◽  
Neurological Disorders ◽  
Cannabinoid Receptors ◽  
System Development ◽  
Endocannabinoid System ◽  
Qualitative Evaluation ◽  
Nervous System Development ◽  
Cannabinoid Compounds ◽  
Anxiety Depression

AbstractCannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. Studies reporting participation of cannabinoids on the regulation of any step of neurogenesis and the effects of cannabinoid compounds on animal models possessing neurogenesis-dependent features were selected from Medline. Qualitative evaluation of the selected studies indicated that activation of cannabinoid receptors may change neurogenesis in embryonic or adult nervous systems alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. The text offers an overview on the effects of cannabinoids on central nervous system development and the possible links with psychiatric and neurological disorders such as anxiety, depression, schizophrenia, brain ischaemia/stroke and Alzheimer’s disease. An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.

scholarly journals Zebrafish Models of Autosomal Recessive Ataxias

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 836
Author(s):  
Ana Quelle-Regaldie ◽  
Daniel Sobrido-Cameán ◽  
Antón Barreiro-Iglesias ◽  
María Jesús Sobrido ◽  
Laura Sánchez
Keyword(s):  
Animal Models ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
System Development ◽  
Rapid Development ◽  
Nervous System Development ◽  
Central Nervous System Development ◽  
Cellular Processes ◽  
Recessive Disorders

Autosomal recessive ataxias are much less well studied than autosomal dominant ataxias and there are no clearly defined systems to classify them. Autosomal recessive ataxias, which are characterized by neuronal and multisystemic features, have significant overlapping symptoms with other complex multisystemic recessive disorders. The generation of animal models of neurodegenerative disorders increases our knowledge of their cellular and molecular mechanisms and helps in the search for new therapies. Among animal models, the zebrafish, which shares 70% of its genome with humans, offer the advantages of being small in size and demonstrating rapid development, making them optimal for high throughput drug and genetic screening. Furthermore, embryo and larval transparency allows to visualize cellular processes and central nervous system development in vivo. In this review, we discuss the contributions of zebrafish models to the study of autosomal recessive ataxias characteristic phenotypes, behavior, and gene function, in addition to commenting on possible treatments found in these models. Most of the zebrafish models generated to date recapitulate the main features of recessive ataxias.

scholarly journals From the Clinic to the Laboratory, and Back Again: Investigations on Cannabinoids and Endocannabinoid System Modulators for Treating Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Kurt Leroy Hoffman
Keyword(s):  
Animal Models ◽  
Outcome Measures ◽  
Clinical Studies ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Clinical Work ◽  
Clinical Results ◽  
Cognitive Outcome ◽  
Experimental Drugs ◽  
First Results

The present mini-review focuses on animal models of schizophrenia that have explored the effects of cannabidiol (CBD; a non-psychoactive component of cannabis) or the pharmacological manipulation of the endocannabinoid system on behavioral and cognitive outcome measures. First, results of some relevant clinical studies in this area are summarized, and then pre-clinical work on animal models of schizophrenia based on NMDA receptor antagonism or neurodevelopmental manipulations are discussed. A brief overview is given of the theoretical framework on which these models are based, along with a concise summary of results that have been obtained. Clinical results using CBD for schizophrenia seem promising and its effects in animal models of schizophrenia support its potential as a useful pharmacotherapy. Animal models have been paramount for elucidating the actions of CBD and the function of the endocannabinoid system and for identifying novel pharmacological targets, such as cannabinoid receptors and anandamide. However, more attention needs to be placed on defining and applying independent variables and outcome measures that are comparable between pre-clinical and clinical studies. The objective of this review is, on the one hand, to emphasize the potential of such models to predict clinical response to experimental drugs, and on the other hand, to highlight areas in which research on such models could be improved.

scholarly journals Neuroprotective Properties of Cannabinoids in Cellular and Animal Models: Hypotheses and Facts

2020 ◽  
Author(s):  
Lucas D. Udovin ◽  
Andrea Aguilar ◽  
Tamara Kobiec ◽  
María I. Herrera ◽  
Santiago Perez Lloret ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Cannabinoid Receptors ◽  
Neuronal Loss ◽  
Cholinergic Neurons ◽  
Endocannabinoid System ◽  
Lipid Mediators ◽  
New Drugs ◽  
Memory And Attention ◽  
Neuroprotective Drugs

Progressive neuronal loss is a typical characteristic of neurodegenerative diseases. In Parkinson’s disease, the loss of dopaminergic neurons in the basal ganglia results in impaired mobility and flawed muscle control. The loss of cholinergic neurons largely in the basal forebrain contributes to memory and attention deficits and the overall cognitive impairment in Alzheimer’s disease. This being said, neuroprotective drugs should be expected to preserve and/or restore the functions affected by neuronal loss, and substantially prevent cell death. The endocannabinoid system, comprising lipid mediators able to bind to and activate cannabinoid receptors, has emerged as a therapeutic target of potential interest in a variety of central nervous system diseases. Palmitoylethanolamide (PEA) is one of the most important endocannabinoids, which has a key role in modulating oxidative stress and inflammatory response with neuroprotective potential in neurological disorders. Neurodegenerative diseases undergo varied, progressive stages. The current therapeutical approaches are beginning to fall short when it comes to meet the expected results, urging to either develop or identify or develop new effective treatments. This chapter discusses the neuroprotective potential of new drugs, aiming to shed some light on their proposed mechanism of action and their effect in cellular and animal models of neurodegeneration.

scholarly journals Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence

2022 ◽  
Vol 12 (1) ◽  
pp. 101
Author(s):  
Riccardo Bortoletto ◽  
Matteo Balestrieri ◽  
Sagnik Bhattacharyya ◽  
Marco Colizzi
Keyword(s):  
Safety Profile ◽  
Cannabinoid Receptors ◽  
Human Study ◽  
Endocannabinoid System ◽  
Human Studies ◽  
Acute Seizures ◽  
Cannabinoid Compounds ◽  
Seizure Episode ◽  
Animal Models Of Epilepsy ◽  
Significant Attention

Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA’s role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy.

scholarly journals SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

2021 ◽  
Vol 14 ◽  
Author(s):  
Milena Stevanovic ◽  
Danijela Drakulic ◽  
Andrijana Lazic ◽  
Danijela Stanisavljevic Ninkovic ◽  
Marija Schwirtlich ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Adult Neurogenesis ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Glial Differentiation ◽  
Neural Lineage ◽  
Stage Of Development ◽  
Sox Proteins

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.

scholarly journals Role of the Endocannabinoid System in the Central Regulation of Nonmammalian Vertebrate Reproduction

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Erika Cottone ◽  
Valentina Pomatto ◽  
Patrizia Bovolin
Keyword(s):  
Animal Models ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Central Regulation ◽  
Signalling Molecules ◽  
Reproductive Control ◽  
Amphibian Reproduction ◽  
Multiple Levels ◽  
Insight Into

The endocannabinoid system (ECS) has a well-documented pivotal role in the control of mammalian reproductive functions, by acting at multiple levels, that is, central (CNS) and local (gonads) levels. Since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, in the present paper we review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, focussing in particular on the central regulation of teleost and amphibian reproduction. The morphofunctional distribution of brain cannabinoid receptors will be discussed in relation to other crucial signalling molecules involved in the control of reproductive functions, such as GnRH, dopamine, aromatase, and pituitary gonadotropins.

scholarly journals Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa)

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Lena-Louise Schuele ◽  
Britta Schuermann ◽  
Andras Bilkei-Gorzo ◽  
Sara Gorgzadeh ◽  
Andreas Zimmer ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mouse Strains ◽  
Specific Cell ◽  
Experimental Conditions ◽  
Diacylglycerol Lipase

AbstractThe endocannabinoid system modulates adult hippocampal neurogenesis by promoting the proliferation and survival of neural stem and progenitor cells (NSPCs). This is demonstrated by the disruption of adult neurogenesis under two experimental conditions: (1) NSPC-specific deletion of cannabinoid receptors and (2) constitutive deletion of the enzyme diacylglycerol lipase alpha (DAGLa) which produces the endocannabinoid 2-arachidonoylglycerol (2-AG). However, the specific cell types producing 2-AG relevant to neurogenesis remain unknown. Here we sought to identify the cellular source of endocannabinoids in the subgranular zone of the dentate gyrus (DG) in hippocampus, an important neurogenic niche. For this purpose, we used two complementary Cre-deleter mouse strains to delete Dagla either in neurons, or in astroglia and NSPCs. Surprisingly, neurogenesis was not altered in mice bearing a deletion of Dagla in neurons (Syn-Dagla KO), although neurons are the main source for the endocannabinoids in the brain. In contrast, a specific inducible deletion of Dagla in NPSCs and astrocytes (GLAST-CreERT2-Dagla KO) resulted in a strongly impaired neurogenesis with a 50% decrease in proliferation of newborn cells. These results identify Dagla in NSPCs in the DG or in astrocytes as a prominent regulator of adult hippocampal neurogenesis. We also show a reduction of Daglb expression in GLAST-CreERT2-Dagla KO mice, which may have contributed to the neurogenesis phenotype.

scholarly journals Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

2016 ◽  
Vol 4 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Shikshya Shrestha ◽  
Steven M. Offer
Keyword(s):  
Brain Development ◽  
Neurological Disorders ◽  
System Development ◽  
Neuronal Cell ◽  
Autism Spectrum ◽  
Nervous System Development ◽  
Adult Brain ◽  
Epigenetic Therapy ◽  
Gabaergic Neurotransmission ◽  
Epigenetic Regulations

The GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotransmission, both excitatory and inhibitory, in neurogenesis and central nervous system development including its control of neuronal cell proliferation and migration, synaptogenesis, dendrite formation and branching, and new neuronal cell integration in the adult brain. There has been remarkable progress in understanding the epigenetic regulations of GABAergic genes and their aberrant expressions in various neurological disorders such as autism spectrum disorder, Rett's syndrome, schizophrenia and PWS. The roles of histone modifications, chromatin looping and gene methylation have been implicated in altered regulations of key genes in the GABAergic pathway. Taken together, they affect the functioning of GABAergic neurotransmission and disrupt various events in brain development. Here, we focus on the role of GABAergic neurotransmission in brain development and on how various genetic and epigenetic events regulate the GABAergic genes in pre- and postnatal brain. We also discuss how these regulatory mechanisms contribute to the pathogenesis of neurological disorders and, therefore, can be used in the development of potential epigenetic therapy for these diseases.

scholarly journals Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities

2012 ◽  
Vol 367 (1607) ◽  
pp. 3353-3363 ◽  
Author(s):  
Roger G. Pertwee
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Symptomatic Relief ◽  
Endocannabinoid System ◽  
Cancer Drug ◽  
Receptor Agonists ◽  
Underlying Causes ◽  
Anxiety Depression ◽  
Lateral Sclerosis ◽  
Stimulation Of

Human tissues express cannabinoid CB 1 and CB 2 receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB 1 /CB 2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ 9 -tetrahydrocannabinol ( Δ 9 -THC)) and Sativex ( Δ 9 -THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB 2 receptors, and/or (v) adjunctive ‘multi-targeting’.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

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