Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition

Abstract Postmortem and neuroimaging studies show low levels of cortical muscarinic M1 receptors (CHRM1) in patients with schizophrenia which is significant because CHRM signalling has been shown to change levels of gene expression and cortical gene expression is altered in schizophrenia. We decided...

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Autores principales:	Brian Dean, Elizabeth Scarr
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/f5d1a6cc2fbf49c198d455a4481819e1
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spelling	oai:doaj.org-article:f5d1a6cc2fbf49c198d455a4481819e12021-12-02T18:49:53ZChanges in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition10.1038/s41537-021-00174-z2334-265Xhttps://doaj.org/article/f5d1a6cc2fbf49c198d455a4481819e12021-09-01T00:00:00Zhttps://doi.org/10.1038/s41537-021-00174-zhttps://doaj.org/toc/2334-265XAbstract Postmortem and neuroimaging studies show low levels of cortical muscarinic M1 receptors (CHRM1) in patients with schizophrenia which is significant because CHRM signalling has been shown to change levels of gene expression and cortical gene expression is altered in schizophrenia. We decided to identify CHRM1-mediated changes in cortical gene expression by measuring levels of RNA in the cortex of the Chrm1−/− mouse (n = 10), where there would be no signalling by that receptor, and in wild type mouse (n = 10) using the Affymetrix Mouse Exon 1.0 ST Array. We detected RNA for 15,501 annotated genes and noncoding RNA of which 1,467 RNAs were higher and 229 RNAs lower in the cortex of the Chrm1− /− mouse. Pathways and proteins affected by the changes in cortical gene expression in the Chrm1−/− are linked to the molecular pathology of schizophrenia. Our human cortical gene expression data showed 47 genes had altered expression in Chrm1−/− mouse and the frontal pole from patients with schizophrenia with the change in expression of 44 genes being in opposite directions. In addition, genes with altered levels of expression in the Chrm1− /− mouse have been shown to affect amyloid precursor protein processing which is associated with the pathophysiology of Alzheimer’s disease, and 69 genes with altered expression in the Chrm1− /− mouse are risk genes associated with human cognitive ability. Our findings argue CHRM1-mediated changes in gene expression are relevant to the pathophysiologies of schizophrenia and Alzheimer’s disease and the maintenance of cognitive ability in humans.Brian DeanElizabeth ScarrNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 7, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Brian Dean Elizabeth Scarr Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
description	Abstract Postmortem and neuroimaging studies show low levels of cortical muscarinic M1 receptors (CHRM1) in patients with schizophrenia which is significant because CHRM signalling has been shown to change levels of gene expression and cortical gene expression is altered in schizophrenia. We decided to identify CHRM1-mediated changes in cortical gene expression by measuring levels of RNA in the cortex of the Chrm1−/− mouse (n = 10), where there would be no signalling by that receptor, and in wild type mouse (n = 10) using the Affymetrix Mouse Exon 1.0 ST Array. We detected RNA for 15,501 annotated genes and noncoding RNA of which 1,467 RNAs were higher and 229 RNAs lower in the cortex of the Chrm1− /− mouse. Pathways and proteins affected by the changes in cortical gene expression in the Chrm1−/− are linked to the molecular pathology of schizophrenia. Our human cortical gene expression data showed 47 genes had altered expression in Chrm1−/− mouse and the frontal pole from patients with schizophrenia with the change in expression of 44 genes being in opposite directions. In addition, genes with altered levels of expression in the Chrm1− /− mouse have been shown to affect amyloid precursor protein processing which is associated with the pathophysiology of Alzheimer’s disease, and 69 genes with altered expression in the Chrm1− /− mouse are risk genes associated with human cognitive ability. Our findings argue CHRM1-mediated changes in gene expression are relevant to the pathophysiologies of schizophrenia and Alzheimer’s disease and the maintenance of cognitive ability in humans.
format	article
author	Brian Dean Elizabeth Scarr
author_facet	Brian Dean Elizabeth Scarr
author_sort	Brian Dean
title	Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
title_short	Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
title_full	Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
title_fullStr	Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
title_full_unstemmed	Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
title_sort	changes in cortical gene expression in the muscarinic m1 receptor knockout mouse: potential relevance to schizophrenia, alzheimer’s disease and cognition
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f5d1a6cc2fbf49c198d455a4481819e1
work_keys_str_mv	AT briandean changesincorticalgeneexpressioninthemuscarinicm1receptorknockoutmousepotentialrelevancetoschizophreniaalzheimersdiseaseandcognition AT elizabethscarr changesincorticalgeneexpressioninthemuscarinicm1receptorknockoutmousepotentialrelevancetoschizophreniaalzheimersdiseaseandcognition
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Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition

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