Cholinergic Senescence in the Ts65Dn Mouse Model for Down Syndrome.
Cholinergic neurons
Down syndrome
Muscarinic receptors
Premature aging
Senescence
Ts65Dn
c-fos
Journal
Neurochemical research
ISSN: 1573-6903
Titre abrégé: Neurochem Res
Pays: United States
ID NLM: 7613461
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
19
01
2022
accepted:
14
06
2022
revised:
08
06
2022
pubmed:
30
6
2022
medline:
16
9
2022
entrez:
29
6
2022
Statut:
ppublish
Résumé
Down syndrome (DS) induces a variable phenotype including intellectual disabilities and early development of Alzheimer's disease (AD). Moreover, individuals with DS display accelerated aging that affects diverse organs, among them the brain. The Ts65Dn mouse is the most widely used model to study DS. Progressive loss of cholinergic neurons is one of the hallmarks of AD present in DS and in the Ts65Dn model. In this study, we quantify the number of cholinergic neurons in control and Ts65Dn mice, observing a general reduction in their number with age but in particular, a greater loss in old Ts65Dn mice. Increased expression of the m1 muscarinic receptor in the hippocampus counteracts this loss. Cholinergic neurons in the Ts65Dn mice display overexpression of the early expression gene c-fos and an increase in the expression of β-galactosidase, a marker of senescence. A possible mechanism for senescence induction could be phosphorylation of the transcription factor FOXO1 and its retention in the cytoplasm, which we are able to confirm in the Ts65Dn model. In our study, using Ts65Dn mice, we observe increased cholinergic activity, which induces a process of early senescence that culminates in the loss of these neurons.
Identifiants
pubmed: 35767135
doi: 10.1007/s11064-022-03659-0
pii: 10.1007/s11064-022-03659-0
pmc: PMC9470680
doi:
Substances chimiques
Cholinergic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3076-3092Informations de copyright
© 2022. The Author(s).
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