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Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients - PubMed

Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients

Cynthia Shannon Weickert et al. Schizophr Res. 2008 Jan.

Abstract

Genetic and molecular studies indicate that dysbindin-1 plays a role in the pathophysiology of schizophrenia. We examined dysbindin-1 mRNA in the hippocampal formation of patients with schizophrenia and found reduced expression in dentate granule and polymorph cells and in hippocampal field CA3, but not in CA1. Furthermore, there were positive correlations between dysbindin-1 mRNA and expression of synaptic markers known to be reduced in schizophrenia. Our results indicate that previously reported dysbindin-1 protein reductions may be due in part to decreased dysbindin-1 mRNA and that reduced dysbindin-1 may contribute to hippocampal formation synaptic pathology in schizophrenia.

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Figures

Figure 1
Figure 1

Autoradiographic film images of the hybridization of dysbindin-1 riboprobe in human hippocampal formation with the adjacent section from the same brain are shown (panels A &B). Panel A is taken shows the image from the antisense strand and panel B shows the image from the sense strand control.

Figure 2
Figure 2

Autoradiographic film images of the hybridization of dysbindin-1 riboprobe in human hippocampal formation are shown (panels A &B). Panel A is taken from a normal control and panel B from a patient with schizophrenia. The subregions at the midbody level of the hippocampal formation demonstrate different expression levels of dysbindin-1 mRNA. Note the intense hybridization signal in the CA3 and DGh subfields. A distinct but fairly thin line of dysbindin-1 mRNA label is found overlying the DGg (panel A & B). The CA1 region has a modest dysbindin-1 hybridization signal. Scale bar = 1 mm. Panel C: Bar graph shows the mean OD reading from dysbindin-1 mRNA signal expressed as ηCi/g radioactivity. Significant differences between controls (blue bars) and schizophrenia patients (red bars) mRNA are found in the DG (mean (SEM) =16.3(1.2), 12.2 (1.8), respectively, p=0.04), DGh (mean (SEM) = 16.6(2.0), 10.4(1.6), respectively; p=0.02), and CA3 (mean (SEM) = 24.3(3.9), 14.9(2.6), respectively; p=0.03) subregions. There were no significant changes between the groups for CA1 mRNA (mean (SEM) = 9.4(0.43), 8.4(0.58), respectively; p>0.05).

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