GAD mRNA in Orbital Prefrontal Cortex and Anterior Cingulate Cortex in Alcoholics Compared with Nonpsychiatric Controls: A Negative Postmortem Study

Alcohol increases inhibitory neurotransmission, an effect mediated through GABA receptors. With chronic alcohol exposure, the inhibitory effects diminish. Glutamic acid decarboxylase (GAD) catalyzes glutamate in the synthesis of GABA. We sought to determine the amount of GAD mRNA in anterior cingula...

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Bibliographic Details
Published inJournal of psychiatry and brain science Vol. 4; no. 2
Main Authors Underwood, Mark D, Bakalian, Mihran J, Dwork, Andrew J, Min, Eli, Mann, J John, Arango, Victoria
Format Journal Article
LanguageEnglish
Published England 2019
Subjects
alcohol
GABA
postmortem
human
in situ hybridization
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Summary:Alcohol increases inhibitory neurotransmission, an effect mediated through GABA receptors. With chronic alcohol exposure, the inhibitory effects diminish. Glutamic acid decarboxylase (GAD) catalyzes glutamate in the synthesis of GABA. We sought to determine the amount of GAD mRNA in anterior cingulate cortex (BA24) and orbital prefrontal cortex (BA45) of medication-free alcoholics and nonpsychiatric controls postmortem. Studies were performed in 16 pairs of nonpsychiatric controls and alcoholics, matched for age, sex and PMI. DSM-IV diagnosis of alcohol use disorder (AUD) was made by the SCID I in a psychological autopsy. Frozen blocks of BA24 or BA45 were sectioned (10 µm) for hybridization of S-labelled riboprobe for GAD mRNA and autoradiograms were analyzed by quantitative densitometry. Three isodensity bands of labeling were evident, with different relative amounts of GAD and GAD (outer and inner, predominantly GAD , intermediate predominantly GAD ), and the isodensity bands were analyzed separately. GAD mRNA levels were not different between alcoholics and controls in the gray matter of BA24 ( = 0.53) or BA45 ( = 0.84) or in any of the three isodensity bands in which the GAD mRNA was distributed. GAD mRNA in white matter underlying either region was also not different in alcoholics ( > 0.05). GAD mRNA levels did not correlate with age, sex or duration of alcoholism in either BA24 or BA45. Effects on inhibitory neurotransmission in alcoholics do not appear to be associated with change in the levels of GAD or GAD mRNA.
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AUTHOR CONTRIBUTIONS
VA, JJM and MDU designed the study. All authors contributed to the acquisition, analysis and interpretation of the data and drafted the manuscript, revising it critically for important intellectual content. MDU and MJB wrote the paper with input from all authors. All authors provided final approval of the published version of the manuscript, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
ISSN:2398-385X
2398-385X
DOI:10.20900/jpbs.20190007