Insulin-like growth factor I sensitization rejuvenates sleep patterns in old mice.
Aging
Cortical activation
IGF-I
Orexinergic neurons
Rejuvenation
Sleep
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
03
03
2022
accepted:
06
05
2022
pubmed:
24
5
2022
medline:
2
11
2022
entrez:
23
5
2022
Statut:
ppublish
Résumé
Sleep disturbances are common during aging. Compared to young animals, old mice show altered sleep structure, with changes in both slow and fast electrocorticographic (ECoG) activity and fewer transitions between sleep and wake stages. Insulin-like growth factor I (IGF-I), which is involved in adaptive changes during aging, was previously shown to increase ECoG activity in young mice and monkeys. Furthermore, IGF-I shapes sleep architecture by modulating the activity of mouse orexin neurons in the lateral hypothalamus (LH). We now report that both ECoG activation and excitation of orexin neurons by systemic IGF-I are abrogated in old mice. Moreover, orthodromical responses of LH neurons are facilitated by either systemic or local IGF-I in young mice, but not in old ones. As orexin neurons of old mice show dysregulated IGF-I receptor (IGF-IR) expression, suggesting disturbed IGF-I sensitivity, we treated old mice with AIK3a305, a novel IGF-IR sensitizer, and observed restored responses to IGF-I and rejuvenation of sleep patterns. Thus, disturbed sleep structure in aging mice may be related to impaired IGF-I signaling onto orexin neurons, reflecting a broader loss of IGF-I activity in the aged mouse brain.
Identifiants
pubmed: 35604612
doi: 10.1007/s11357-022-00589-1
pii: 10.1007/s11357-022-00589-1
pmc: PMC9616996
doi:
Substances chimiques
Orexins
0
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2243-2257Informations de copyright
© 2022. The Author(s), under exclusive licence to American Aging Association.
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