Document Detail


GABA, gamma-hydroxybutyric acid, and neurological disease.
MedLine Citation:
PMID:  12891648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA is converted from glutamic acid by the action of glutamic acid decarboxylase (GAD) of which two isoforms exist GAD65 and GAD67. GABA then is broken down, both within the cell and in the synaptic cleft by GABA transaminase to form succinic semialdehyde. In turn, succinic semialdehyde is converted either to succinic acid by succinic semialdehyde dehydrogenase or into gamma-hydroxybutyric acid (GHB) by succinic semialdehyde reductase. Because GABA modulates the majority of inhibition that is ongoing in the brain, perturbations in GABAergic inhibition have the potential to result in seizures. Therefore, the most common disorder in which GABA is targeted as a treatment is epilepsy. However, other disorders such as psychiatric disease, spasticity, and stiff-person syndrome all have been related to disorders of GABAergic function in the brain. This review covers the roles of GABAergic neurotransmission in epilepsy, anxiety disorders, schizophrenia, stiff-person syndrome, and premenstrual dysphoric disorder. In the final section of this review, the GABA metabolite GHB is discussed in terms of its physiological significance and its role in epilepsy, sleep disorders, drug and alcohol addiction, and an inborn error of GABA metabolism, succinic semialdehyde dehydrogenase deficiency.
Authors:
C Guin Ting Wong; Teodoro Bottiglieri; O Carter Snead
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review    
Journal Detail:
Title:  Annals of neurology     Volume:  54 Suppl 6     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2003  
Date Detail:
Created Date:  2003-07-31     Completed Date:  2003-12-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S3-12     Citation Subset:  IM    
Affiliation:
Institute of Medical Sciences, University of Toronto, Faculty of Medicine and Brain and Behavior Research Program, Hospital for Sick Children, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Oxidoreductases / deficiency,  genetics
Animals
Humans
Mice
Nervous System Diseases / genetics*,  metabolism
Receptors, GABA-A / physiology
Receptors, GABA-B / physiology
Sodium Oxybate / metabolism*,  pharmacology
Succinate-Semialdehyde Dehydrogenase
gamma-Aminobutyric Acid / physiology*
Chemical
Reg. No./Substance:
0/Receptors, GABA-A; 0/Receptors, GABA-B; 502-85-2/Sodium Oxybate; 56-12-2/gamma-Aminobutyric Acid; EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.1.24/ALDH5A1 protein, human; EC 1.2.1.24/Succinate-Semialdehyde Dehydrogenase

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