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Decreased BDNF, trkB-TK+ and GAD<sub>67</sub> mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders

2011· article· en· 353 citations· W1656703530 on OpenAlex· 10.1503/jpn.100048

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Canadian venueIt was published in a Canadian venue.

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Opus teacher head0.018
GPT teacher head0.242
Teacher spread
0.224 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

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.

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The record

Venue
Journal of Psychiatry and Neuroscience
Topic
Nerve injury and regeneration
Field
Neuroscience
Canadian institutions
Funders
University of New South WalesStanley Medical Research Institute
Keywords
Glutamate decarboxylaseHippocampusInternal medicineEndocrinologyDentate gyrusTropomyosin receptor kinase BBipolar disorderBrain-derived neurotrophic factorIn situ hybridizationSubiculumSchizophrenia (object-oriented programming)Entorhinal cortexPsychologyPrefrontal cortexNeurotrophic factorsNeuroscienceBiologyMedicinePsychiatryMessenger RNAReceptorLithium (medication)Enzyme
Has abstract in OpenAlex
yes