Decreased cortical muscarinic M1 receptors in schizophrenia are associated with changes in gene promoter methylation, mRNA and gene targeting microRNA

E Scarr; JM Craig; MJ Cairns; MS Seo; JC Galati; NJ Beveridge; A Gibbons; S Juzva; B Weinrich; M Parkinson-Bates; AP Carroll; R Saffery; B Dean

Journal article

Decreased cortical muscarinic M1 receptors in schizophrenia are associated with changes in gene promoter methylation, mRNA and gene targeting microRNA

E Scarr, JM Craig, MJ Cairns, MS Seo, JC Galati, NJ Beveridge, A Gibbons, S Juzva, B Weinrich, M Parkinson-Bates, AP Carroll, R Saffery, B Dean

Translational Psychiatry | Published : 2013

DOI: 10.1038/tp.2013.3

Download PDF

Abstract

Many studies have shown decreased cortical muscarinic M1 receptors (CHRM1) in schizophrenia (Sz), with one study showing Sz can be separated into two populations based on a marked loss of CHRM1 (∼75%) in ∼25% of people (Def-Sz) with the disorder. To better understand the mechanism contributing to the loss of CHRM1 in Def-Sz, we measured specific markers of gene expression in the cortex of people with Sz as a whole, people differentiated into Def-Sz and people with Sz that do not have a deficit in cortical CHRM1 (Non-Def-Sz) and health controls. We now report that cortical CHRM1 gene promoter methylation and CHRM1 mRNA are decrease in Sz, Def-Sz and Non-Def-Sz but levels of the micro RNA (miR..

View full abstract

University of Melbourne Researchers

Jeff Craig Author

Richard Saffery Author

Brian Dean Author Florey Department of Neuroscience and Mental Health

Related Projects (3)

Studies on the mechanisms by which muscarinic receptors might cause schizophrenia

Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the population. This project will help define changes in the..

Muscarinic Receptors in Mood Disorders

The causes of bipolar disorder and major depressive disorder, which effect many Australians, remain unknown. We have recently shown decrease..

The cause of psychiatric disease

The Applicant seeks to understand the causes of the schizophrenia, bipolar disorder and major depressive disorder, which affect over 20% of ..

Grants

Awarded by National Science Foundation

Funding Acknowledgements

The authors are grateful for the excellent technical assistance of Mr Geoff Pavey. Tissues were received from the Victorian Brain Bank Network, which is supported by the Mental Health Research Institute, The Alfred, Victorian Forensic Institute of Medicine and The University of Melbourne and funded by Australia's National Health and Medical Research Council, Helen Macpherson Smith Trust, Parkinson's Victoria and Perpetual Philanthropic Services. Sources of support: BD is an NHMRC Senior Research Fellow (APP1002240). ES is an ARC Future Fellow (FT100100689). MSS is a recipient of a University of Melbourne International Research Scholarship. This research was principally funded by the NHMRC (Project Grant no. 509333 and 628669) but was also funded in part by the Victorian Government's Operational Infrastructure Support Programme, the Rebecca L Cooper Medical Research Foundation and the Wood's Family Research Program.