In:
Current Neuropharmacology, Bentham Science Publishers Ltd., Vol. 21, No. 3 ( 2023-03), p. 740-760
Abstract:
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 nondemented
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 ageand
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.
Type of Medium:
Online Resource
ISSN:
1570-159X
DOI:
10.2174/1570159X21666221207091209
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2023
detail.hit.zdb_id:
2119376-9
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