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

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

Mia Thompson Ray et al. J Psychiatry Neurosci. 2011 May.

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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Figures

Fig. 1

The top 4 panels show the distribution of brain-derived neurotrophic factor (BDNF) mRNA in (A) control, (B) schizophrenia, (C) bipolar disorder and (D) major depression groups. Middle panels display the distribution of tyrosine kinase receptor (trkB-TK+) mRNA in (E) control, (F) schizophrenia, (G) bipolar disorder and (H) major depression groups, and the bottom panels show the distribution of glutamic acid decarboxylase (GAD67) mRNA in (I) control, (J) schizophrenia, (K) bipolar disorder and (L) major depression groups.

Fig. 2

(A) Mean brain-derived neurotrophic factor (BDNF) mRNA levels in CA4 in the diagnostic groups and controls. (B) Mean tyrosine kinase receptor (trkB-TK+) mRNA levels in CA4 and layer II of the entorhinal cortex in the diagnostic groups and controls. (C) Mean glutamic acid decarboxylase (GAD67) mRNA levels in the dentate gyrus and CA4 of the diagnostic groups and controls. Standard error is represented by error bars. B = bipolar disorder; CA = cornu ammonis subfield; D = major depression; N = unaffected controls; S = schizophrenia. (*p ≤ 0.05). All reported significance values are in comparison to controls.

Fig. 3

Mean brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor (trkB-TK+) and glutamic acid decarboxylase (GAD67) mRNA levels of individuals taking antidepressants at the time of death, patients not taking antidepressants at the time of death and unaffected controls in the dentate gyrus and cornu ammonis (CA) subfield 4. Standard error is represented by error bars (*p ≤ 0.05; **p ≤ 0.01).

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