SMAD4 protein is decreased in the dorsolateral prefrontal and anterior cingulate cortices in schizophrenia

Abstract

Objectives

Signal transduction through the mothers against decapentaplegic (SMAD) is a family of signal transduction factors that mediate signalling of the transforming growth factor B (TGFB)-superfamily of cell regulatory proteins. A recent transcriptomic analysis of post-mortem, cortical tissue from subjects with schizophrenia found decreased mRNA expression of SMAD2 and SMAD4 in the dorsolateral prefrontal cortex (DLPFC) associated with the disorder. To expand this initial finding, we sought to determine whether SMAD2 and SMAD4 protein were also altered in the cortex from subjects with schizophrenia.

Methods

Western blotting was used to measure SMAD2 and SMAD4 protein levels in DLPFC and anterior cingulate cortex (ACC) taken post-mortem from subjects with schizophrenia (n = 20) and matched control (n = 20) subjects.

Results

Compared to controls, levels of SMAD4 were 25% lower in the DLPFC and 38% lower in the ACC from subjects with schizophrenia. By contrast, SMAD2 levels were not altered in either DLPFC or ACC.

Conclusions

Our finding of lower SMAD4 protein in the cortex suggests there are likely to be abnormalities in cortical TGFB-superfamily signalling in schizophrenia.

Keywords:

• SMAD
• transforming growth factor
• schizophrenia
• anti-inflammatory cytokines
• post-mortem

Acknowledgments

The authors gratefully acknowledge the Victorian Brain Bank as the source of the human post-mortem tissue used in this study. The authors also acknowledge Geoff Pavey for his technical support and curation of the human brain tissue and Clare Duncan and Monica Bos for their technical assistance.

Disclosure statement

The authors declare no conflicts of interest associated with this study.

Additional information

Funding

This project was supported by the National Health and Medical Research Council (NHMRC Australia; Project Grant 1048544 and Fellowship (BD) 1002240), the Victorian Government’s Operational Infrastructure Support Programme.