| SSADH deficiency leads to elevated extracellular GABA levels and increased GABAergic neurotransmission in the mouse cerebral cortex. | |
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MedLine Citation:
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PMID: 18696252 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inherited disorder in which patients display neurodevelopmental retardation, ataxia, and epileptic seizures. The recently engineered SSADH knock-out (KO) mouse models the severe form of the human disorder. The SSADH enzyme participates in the breakdown of the inhibitory neurotransmitter GABA, and studies have shown increases in brain GABA and downregulation of GABA(A) receptor beta(2) subunits in the cerebral cortex of these mice. Here, we used brain slice electrophysiology to investigate the alterations in GABA neurotransmission in SSADH KO mouse cortex. In layer 2/3 pyramidal cells, spontaneous inhibitory postsynaptic currents (IPSCs), reflecting activity of GABAergic synaptic contacts, were normal in SSADH KO mice. Also, IPSCs evoked by electrical single-axon stimulation in KO mice were normal. In contrast, tonic inhibition mediated by presumed extrasynaptic GABA(A) receptors was strongly increased, indicating significantly raised extracellular GABA levels. The excessive cortical GABAergic neurotransmission may participate in the seizure activity in SSADH deficiency. |
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Authors:
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K R Drasbek; I Vardya; M Delenclos; K M Gibson; K Jensen |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-08-15 |
Journal Detail:
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Title: Journal of inherited metabolic disease Volume: 31 ISSN: 1573-2665 ISO Abbreviation: J. Inherit. Metab. Dis. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-05 Completed Date: 2009-04-24 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 7910918 Medline TA: J Inherit Metab Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 662-8 Citation Subset: IM |
Affiliation:
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Synaptic Physiology Laboratory, Institute of Physiology and Biophysics, University of Aarhus, Aarhus, Denmark. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Cerebral Cortex / metabolism* Electrophysiology / methods Female Gene Expression Regulation* Heterozygote Humans Male Mice Mice, Knockout Models, Biological Receptors, GABA-A / metabolism* Succinate-Semialdehyde Dehydrogenase / deficiency*, metabolism gamma-Aminobutyric Acid / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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NS 40270/NS/NINDS NIH HHS; R01 NS040270-07/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, GABA-A; 56-12-2/gamma-Aminobutyric Acid; EC 1.2.1.24/Succinate-Semialdehyde Dehydrogenase |
| Comments/Corrections | |
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