Investigating the Role of GABA in Neural Development and Disease Using Mice Lacking GAD67 or VGAT Genes

Normal development and function of the central nervous system involves a balance between excitatory and inhibitory neurotransmission. Activity of both excitatory and inhibitory neurons is modulated by inhibitory signalling of the GABAergic and glycinergic systems. Mechanisms that regulate formation,...

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Published in:International journal of molecular sciences 2022-07, Vol.23 (14), p.7965
Main Authors: Bolneo, Erika, Chau, Pak Yan S., Noakes, Peter G., Bellingham, Mark C.
Format: Article
Language:English
Subjects:
Autism
Binding sites
Brain
Cell cycle
Central nervous system
Chloride channels
Epilepsy
Forebrain
GABA
GABA-receptors
GABAergic transmission
GAD65
GAD67
Mental disorders
Nervous system
Neurogenesis
Neurological diseases
Neurons
Neurotransmission
Neurotransmitters
Review
Schizophrenia
Signal transduction
Spinal cord
Synapses
VGAT
γ-Aminobutyric acid
γ-Aminobutyric acid receptors
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description Normal development and function of the central nervous system involves a balance between excitatory and inhibitory neurotransmission. Activity of both excitatory and inhibitory neurons is modulated by inhibitory signalling of the GABAergic and glycinergic systems. Mechanisms that regulate formation, maturation, refinement, and maintenance of inhibitory synapses are established in early life. Deviations from ideal excitatory and inhibitory balance, such as down-regulated inhibition, are linked with many neurological diseases, including epilepsy, schizophrenia, anxiety, and autism spectrum disorders. In the mammalian forebrain, GABA is the primary inhibitory neurotransmitter, binding to GABA receptors, opening chloride channels and hyperpolarizing the cell. We review the involvement of down-regulated inhibitory signalling in neurological disorders, possible mechanisms for disease progression, and targets for therapeutic intervention. We conclude that transgenic models of disrupted inhibitory signalling—in GAD67+/− and VGAT−/− mice—are useful for investigating the effects of down-regulated inhibitory signalling in a range of neurological diseases.
doi_str_mv 10.3390/ijms23147965
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subjects Autism
Binding sites
Brain
Cell cycle
Central nervous system
Chloride channels
Epilepsy
Forebrain
GABA
GABA-receptors
GABAergic transmission
GAD65
GAD67
Mental disorders
Nervous system
Neurogenesis
Neurological diseases
Neurons
Neurotransmission
Neurotransmitters
Review
Schizophrenia
Signal transduction
Spinal cord
Synapses
VGAT
γ-Aminobutyric acid
γ-Aminobutyric acid receptors
title Investigating the Role of GABA in Neural Development and Disease Using Mice Lacking GAD67 or VGAT Genes
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