| Decreased glutamic acid decarboxylase mRNA expression in prefrontal cortex in Parkinson's disease. | |
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MedLine Citation:
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PMID: 20832408 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Parkinson's disease (PD) patients typically suffer from motor disorders but mild to severe cognitive deficits can also be present. Neuropathology of PD primarily involves loss of dopaminergic neurons in the substantia nigra, pars compacta, although more widespread pathology from the brainstem to the cerebral cortex occurs at different stages of the disease. Cognitive deficits in PD are thought to involve the cerebral cortex, and imaging studies have identified the dorsolateral prefrontal cortex (DLPFC) as a possible site for some of the symptoms. GABAergic neurons in the cerebral cortex play a key role in the modulation of pyramidal neurons and alterations in muscimol binding to GABA(A) receptors have been reported in Brodmann area 9 (BA9) of the prefrontal cortex in PD patients (Nishino et al., 1988). In order to further assess the likelihood that GABAergic activity is altered in the prefrontal cortex in PD, gene expression of the 67 kilodalton isoform of the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD67 encoded by the GAD1 gene), was examined in BA9 of post-mortem brains from 19 patients and 20 controls using isotopic in situ hybridization histochemistry. GAD67 mRNA labeling was examined and quantified on X-ray films and emulsion radioautographs. We show that GAD67 mRNA labeling is significantly lower in PD compared to control cases. Analysis of emulsion radioautographs indicates that GAD67 mRNA labeling is decreased in individual neurons and is not paralleled by a decrease in the number of GAD67 mRNA-labeled neurons. Analysis of expression data from a microarray study performed in 29 control and 33 PD samples from BA9 confirms that GAD67 expression is decreased in PD. Another finding from the microarray study is a negative relationship between GAD67 mRNA expression and age at death. Altogether, the results support the possibility that GABAergic neurotransmission is impaired in the DLPFC in PD, an effect that may be involved in some of the behavioral deficits associated with the disease. |
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Authors:
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Amélie C Lanoue; Alexandra Dumitriu; Richard H Myers; Jean-Jacques Soghomonian |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2010-09-09 |
Journal Detail:
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Title: Experimental neurology Volume: 226 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-15 Completed Date: 2010-10-28 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 207-17 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, 02118, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Aging / physiology Autoradiography Brain Chemistry / physiology Glutamate Decarboxylase / biosynthesis* Humans In Situ Hybridization Male Microarray Analysis Middle Aged Parkinson Disease / enzymology* Prefrontal Cortex / enzymology* RNA, Messenger / biosynthesis* gamma-Aminobutyric Acid / physiology |
| Grant Support | |
ID/Acronym/Agency:
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P30 AG019610-10S1/AG/NIA NIH HHS; P30 AG19610/AG/NIA NIH HHS; R01-NS036711/NS/NINDS NIH HHS; R24 MH 068855/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 56-12-2/gamma-Aminobutyric Acid; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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