期刊
GEROSCIENCE
卷 44, 期 4, 页码 2243-2257出版社
SPRINGER
DOI: 10.1007/s11357-022-00589-1
关键词
Aging; Cortical activation; IGF-I; Orexinergic neurons; Sleep; Rejuvenation
资金
- Ciberned
- MCIN/AEI [SAF2016-76462]
- National Council of Science, Technology and Technological Innovation (CONCYTEC, Peru) through the National Fund for Scientific and Technological Development (FONDECYT, Peru)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2017/14742-0, 2019/03368-5]
Sleep disturbances in aging mice are related to impaired IGF-I signaling onto orexin neurons, and modulation of the activity of orexin neurons in the lateral hypothalamus can improve sleep patterns.
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.
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