Sanfilippo, Cristina;
Giuliano, Loretta;
Castrogiovanni, Paola;
Imbesi, Rosa;
Ulivieri, Martina;
Fazio, Francesco;
Blennow, Kaj;
... Di Rosa, Michelino; + view all
(2023)
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.
Current Neuropharmacology
, 21
(3)
pp. 740-760.
10.2174/1570159X21666221207091209.
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Abstract
Cholinergic hypofunction and sleep disturbance are hallmarks of Alzheimer's disease (AD), a progressive disorder leading to neuronal deterioration. Muscarinic acetylcholine receptor (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 the rapid eye movement (REM) sleep. 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. 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. 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.
| Type: | Article |
|---|---|
| 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 |
| Location: | United Arab Emirates |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.2174/1570159X21666221207091209 |
| Publisher version: | http://dx.doi.org/10.2174/1570159X2166622120709120... |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer’s disease, REM-Sleep; Sleep disturbance; Bioinformatics; CHRM1; CHRM3 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10164251 |
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