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PMID: 21223646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders.

Journal of psychiatry & neuroscience : JPN ·Vol. 36 ·No. 3 ·2011-05-00 ·Pages 195-203

Thompson Ray M, Weickert CS, Wyatt E, Webster MJ

Abstract

Brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor (trkB-TK+) and glutamic acid decarboxylase (GAD67) mRNA levels have previously been found to be reduced in the prefrontal cortex of patients with schizophrenia. To determine whether this reduction extends to other brain regions, we measured the expression levels of BDNF, trkB-TK+ and GAD67 mRNA in regions of the hippocampus, including the dentate gyrus (DG), cornu ammonis subfields (CA1-4), subiculum and entorhinal cortex (EC) of individuals with schizophrenia, bipolar disorder, major depression and unaffected controls. In situ hybridization was performed on postmortem brain tissue obtained from the Stanley Foundation Consortium and analyzed using film-based quantification. Analyses of covariance comparing the expression of mRNA among all groups revealed a significant decrease in BDNF mRNA in CA4 in the bipolar disorder group compared with controls (33%). We found trkB-TK+ mRNA levels to be significantly reduced in CA4 in the schizophrenia group (36%) and in layer II of the EC in the bipolar disorder and major depression groups (28%, 21%, respectively) compared with controls. In addition, GAD67 mRNA levels were reduced in patients with schizophrenia in both the DG (23%) and CA4 (60%) compared with controls. Individuals with major depression also expressed significantly less GAD67 mRNA (44%) compared with controls in CA4 of the hippocampus. It is necessary to account for factors that influence the molecular preservation in postmortem brain tissue, including pH, postmortem interval and tissue storage time. Moreover, there are limitations to the sensitivity of the film-based method of quantification. Our findings show abnormal BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders, indicating that fundamental properties of hippocampal signalling transmission, plasticity and circuitry may be affected in individuals with these major mental illnesses.

MeSH Terms
Adult Analysis of Variance Brain-Derived Neurotrophic Factor/genetics,metabolism Female Glutamate Decarboxylase/genetics,metabolism Hippocampus/metabolism Humans In Situ Hybridization Male Middle Aged Mood Disorders/genetics,metabolism RNA, Messenger/genetics,metabolism Receptor, trkB/genetics,metabolism Schizophrenia/genetics,metabolism
Chemicals
Brain-Derived Neurotrophic Factor RNA, Messenger Receptor, trkB Glutamate Decarboxylase glutamate decarboxylase 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Thompson Ray Mia
Stanley Laboratory of Brain Research, Rockville, MD 20850, USA. [email protected]
Weickert Cynthia Shannon
Wyatt Eugene
Webster Maree J
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Article Info
Journal
Journal of psychiatry & neuroscience : JPN
Abbr.
J Psychiatry Neurosci
ISSN
1488-2434
DOI
10.1503/jpn.100048
Email
[email protected]
Published
2011-05-00
Pages
195-203
Language
English
Region
Canada
NLM ID
9107859
PMCID
PMC3080515
Subset
IM
External Links
PubMed source DOI: 10.1503/jpn.100048 PMC Full Text View journal details
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