Down-regulation of Dickkopf 3, a regulator of the Wnt signalling pathway, in elderly schizophrenic subjects
Article first published online: 10 JUN 2005
Journal of Neurochemistry
Volume 94, Issue 2, pages 520–530, July 2005
How to Cite
Ftouh, S., Akbar, M. T., Hirsch, S. R. and De Belleroche, J. S. (2005), Down-regulation of Dickkopf 3, a regulator of the Wnt signalling pathway, in elderly schizophrenic subjects. Journal of Neurochemistry, 94: 520–530. doi: 10.1111/j.1471-4159.2005.03239.x
- Issue published online: 10 JUN 2005
- Article first published online: 10 JUN 2005
- Received November 19, 2004; revised manuscript received April 11, 2005; accepted April 11, 2005.
- gene expression;
- Wnt signalling
The aetiology of schizophrenia is complex and the pathological mechanisms involved are still not fully understood. The aim of this project was to gain insight into the underlying molecular changes occurring in schizophrenia through the analysis of gene expression. Using suppression subtractive hybridization to isolate differentially expressed genes in superior temporal cortex (BA22), we detected one prominent sequence with reduced expression in schizophrenia and represented in at least nine clones. This was then selected for further validation. This 190-bp partial transcript showed identity to part of the Dickkopf-3 (Dkk3) gene sequence. Differential expression was initially confirmed in BA22 by slot blot hybridization where expression was decreased by 35% (p < 0.026). These results were further authenticated in a larger panel (12 control and 11 schizophrenia cases) using SYBR Green I real-time quantitative RT–PCR, in which a 41% decrease in expression of Dkk3 mRNA in schizophrenia was obtained (p < 0.012). Furthermore, using in situ hybridization, Dkk3 mRNA was shown to be abundantly expressed in cortical neurones, with prominent expression in layers II/III and V/VI of BA22. Dkk3 belongs to a novel family of Dkk proteins, which have been shown to be potent inhibitors of the neurodevelopmental wingless (Wnt) signalling pathway, and is therefore a putative candidate for further investigation into the aetiology of schizophrenia.