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

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

PDF

J Psychiatry Neurosci 2011;36(3):195-203

Mia Thompson Ray, PhD; Cynthia Shannon Weickert, PhD; Eugene Wyatt, BS; Maree J. Webster, PhD

Thompson Ray, Wyatt, Webster — Stanley Laboratory of Brain Research, Rockville, MD; Weickert — Schizophrenia Research Institute, School of Psychiatry, University of New South Wales, Prince of Wales Medical Research Institute, Sydney, Australia

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 bi polar 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.


Submitted Mar. 18, 2010; Revised July 9, Sept. 8, 2010; Accepted Sept. 8, 2010.

Acknowledgments: This work was supported by the Schizophrenia Research Institute, utilizing infrastructure funding from NSW Health, the University of New South Wales School of Psychiatry, and the Prince of Wales Medical Research Institute. This research was also funded by the Stanley Medical Research Institute.

Competing interests: None declared.

Contributors: Drs. Weickert and Webster designed the study. Mr. Wyatt acquired the data, which all authors analyzed. Drs. Thompson Ray and Webster wrote the article. All authors reviewed it and approved publication.

DOI: 10.1503/jpn.100048

Correspondence to: Dr. M. Thompson Ray, Stanley Laboratory of Brain Research, 9800 Medical Center Dr., Rockville, MD 20850; thompsonm@stanleyresearch.org