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

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Version 2 2024-06-04, 13:32
Version 1 2018-07-10, 10:55
journal contribution
posted on 2024-06-04, 13:32 authored by E Scarr, Jeffrey CraigJeffrey Craig, MJ Cairns, MS Seo, JC Galati, NJ Beveridge, A Gibbons, S Juzva, B Weinrich, M Parkinson-Bates, AP Carroll, R Saffery, B Dean
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)-107, a CHRM1 targeting miR, are increased only in Def-Sz. We also report in vitro data strongly supporting the notion that miR-107 levels regulate CHRM1 expression. These data suggest there is a reversal of the expected inverse relationship between gene promoter methylation and CHRM1 mRNA in people with Sz and that a breakdown in gene promoter methylation control of CHRM1 expression is contributing to the global pathophysiology of the syndrome. In addition, our data argues that increased levels of at least one miR, miR-107, is contributing to the marked loss of cortical CHRM1 in Def-Sz and this may be a differentiating pathophysiology. These latter data continue to support the hypothesis that microRNAs (miRNA) have a role in the underlying neurobiology of Sz but argue they are differentially affected in subsets of people within that syndrome.

History

Journal

Translational psychiatry

Volume

3

Article number

e230

Pagination

1-9

Location

London, Eng.

eISSN

2158-3188

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2013, Macmillan Publishers

Publisher

Nature