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Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances

BACKGROUND: Cholinergic hypofunction and sleep disturbance are hallmarks of Alzheimer’s disease (AD), a progressive disorder leading to neuronal deterioration. Muscarinic acetylcholine receptors (M1-5 or mAChRs), expressed in hippocampus and cerebral cortex, play a pivotal role in the aberrant alter...

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Autores principales: Sanfilippo, Cristina, Giuliano, Loretta, Castrogiovanni, Paola, Imbesi, Rosa, Ulivieri, Martina, Fazio, Francesco, Blennow, Kaj, Zetterberg, Henrik, Di Rosa, Michelino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207911/
https://www.ncbi.nlm.nih.gov/pubmed/36475335
http://dx.doi.org/10.2174/1570159X21666221207091209
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author Sanfilippo, Cristina
Giuliano, Loretta
Castrogiovanni, Paola
Imbesi, Rosa
Ulivieri, Martina
Fazio, Francesco
Blennow, Kaj
Zetterberg, Henrik
Di Rosa, Michelino
author_facet Sanfilippo, Cristina
Giuliano, Loretta
Castrogiovanni, Paola
Imbesi, Rosa
Ulivieri, Martina
Fazio, Francesco
Blennow, Kaj
Zetterberg, Henrik
Di Rosa, Michelino
author_sort Sanfilippo, Cristina
collection PubMed
description BACKGROUND: Cholinergic hypofunction and sleep disturbance are hallmarks of Alzheimer’s disease (AD), a progressive disorder leading to neuronal deterioration. Muscarinic acetylcholine receptors (M1-5 or mAChRs), expressed in hippocampus and cerebral cortex, play a pivotal role in the aberrant alterations of cognitive processing, memory, and learning, observed in AD. Recent evidence shows that two mAChRs, M1 and M3, encoded by CHRM1 and CHRM3 genes, respectively, are involved in sleep functions and, peculiarly, in rapid eye movement (REM) sleep. METHODS: We used twenty microarray datasets extrapolated from post-mortem brain tissue of non-demented healthy controls (NDHC) and AD patients to examine the expression profile of CHRM1 and CHRM3 genes. Samples were from eight brain regions and stratified according to age and sex. RESULTS: CHRM1 and CHRM3 expression levels were significantly reduced in AD compared with age- and sex-matched NDHC brains. A negative correlation with age emerged for both CHRM1 and CHRM3 in NDHC but not in AD brains. Notably, a marked positive correlation was also revealed between the neurogranin (NRGN) and both CHRM1 and CHRM3 genes. These associations were modulated by sex. Accordingly, in the temporal and occipital regions of NDHC subjects, males expressed higher levels of CHRM1 and CHRM3, respectively, than females. In AD patients, males expressed higher levels of CHRM1 and CHRM3 in the temporal and frontal regions, respectively, than females. CONCLUSION: Thus, substantial differences, all strictly linked to the brain region analyzed, age, and sex, exist in CHRM1 and CHRM3 brain levels both in NDHC subjects and in AD patients.
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spelling pubmed-102079112023-10-11 Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances Sanfilippo, Cristina Giuliano, Loretta Castrogiovanni, Paola Imbesi, Rosa Ulivieri, Martina Fazio, Francesco Blennow, Kaj Zetterberg, Henrik Di Rosa, Michelino Curr Neuropharmacol Medicine, Neurology, Pharmacology, Neuroscience BACKGROUND: Cholinergic hypofunction and sleep disturbance are hallmarks of Alzheimer’s disease (AD), a progressive disorder leading to neuronal deterioration. Muscarinic acetylcholine receptors (M1-5 or mAChRs), expressed in hippocampus and cerebral cortex, play a pivotal role in the aberrant alterations of cognitive processing, memory, and learning, observed in AD. Recent evidence shows that two mAChRs, M1 and M3, encoded by CHRM1 and CHRM3 genes, respectively, are involved in sleep functions and, peculiarly, in rapid eye movement (REM) sleep. METHODS: We used twenty microarray datasets extrapolated from post-mortem brain tissue of non-demented healthy controls (NDHC) and AD patients to examine the expression profile of CHRM1 and CHRM3 genes. Samples were from eight brain regions and stratified according to age and sex. RESULTS: CHRM1 and CHRM3 expression levels were significantly reduced in AD compared with age- and sex-matched NDHC brains. A negative correlation with age emerged for both CHRM1 and CHRM3 in NDHC but not in AD brains. Notably, a marked positive correlation was also revealed between the neurogranin (NRGN) and both CHRM1 and CHRM3 genes. These associations were modulated by sex. Accordingly, in the temporal and occipital regions of NDHC subjects, males expressed higher levels of CHRM1 and CHRM3, respectively, than females. In AD patients, males expressed higher levels of CHRM1 and CHRM3 in the temporal and frontal regions, respectively, than females. CONCLUSION: Thus, substantial differences, all strictly linked to the brain region analyzed, age, and sex, exist in CHRM1 and CHRM3 brain levels both in NDHC subjects and in AD patients. Bentham Science Publishers 2023-03-08 2023-03-08 /pmc/articles/PMC10207911/ /pubmed/36475335 http://dx.doi.org/10.2174/1570159X21666221207091209 Text en © 2023 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Medicine, Neurology, Pharmacology, Neuroscience
Sanfilippo, Cristina
Giuliano, Loretta
Castrogiovanni, Paola
Imbesi, Rosa
Ulivieri, Martina
Fazio, Francesco
Blennow, Kaj
Zetterberg, Henrik
Di Rosa, Michelino
Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances
title Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances
title_full Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances
title_fullStr Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances
title_full_unstemmed Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances
title_short Sex, Age, and Regional Differences in CHRM1 and CHRM3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer's Disease-related Sleep Disturbances
title_sort sex, age, and regional differences in chrm1 and chrm3 genes expression levels in the human brain biopsies: potential targets for alzheimer's disease-related sleep disturbances
topic Medicine, Neurology, Pharmacology, Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207911/
https://www.ncbi.nlm.nih.gov/pubmed/36475335
http://dx.doi.org/10.2174/1570159X21666221207091209
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