RGD Reference Report - Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. - Rat Genome Database

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

Authors: Thompson Ray, M  Weickert, CS  Wyatt, E  Webster, MJ 
Citation: Thompson Ray M, etal., J Psychiatry Neurosci. 2011 May;36(3):195-203.
RGD ID: 5684778
Pubmed: PMID:21223646   (View Abstract at PubMed)
PMCID: PMC3080515   (View Article at PubMed Central)
DOI: DOI:10.1503/jpn.100048   (Journal Full-text)

BACKGROUND: 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. METHODS: In situ hybridization was performed on postmortem brain tissue obtained from the Stanley Foundation Consortium and analyzed using film-based quantification. Results: 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. LIMITATIONS: 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. CONCLUSION: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
major depressive disorder  IEP 5684778mRNA:decreased expression:depressionRGD 
major depressive disorder  ISONTRK2 (Homo sapiens)5684778; 5684778mRNA:decreased expression:depressionRGD 
schizophrenia  IEP 5684778mRNA:decreased expression:depressionRGD 
schizophrenia  ISONTRK2 (Homo sapiens)5684778; 5684778mRNA:decreased expression:depressionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ntrk2  (neurotrophic receptor tyrosine kinase 2)

Genes (Mus musculus)
Ntrk2  (neurotrophic tyrosine kinase, receptor, type 2)

Genes (Homo sapiens)
NTRK2  (neurotrophic receptor tyrosine kinase 2)


Additional Information