Insulin-like growth factor I sensitization rejuvenates sleep patterns in old mice

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Zegarra-Valdivia, Jonathan A. ; Fernandes, Jansen ; Fernandez de Sevilla, Maria Estrella ; Trueba-Saiz, Angel ; Pignatelli, Jaime ; Suda, Kentaro ; Martinez-Rachadell, Laura ; Maria Fernandez, Ana ; Esparza, Julio ; Vega, Miguel ; Nunez, Angel ; Torres Aleman, Ignacio

• Document type: Journal article
• Source: GEROSCIENCE; v. 44, n. 4, p. 15-pg., 2022-05-23.

Abstract

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. (AU)

• FAPESP's process: 17/14742-0 - Effects of prenatal exercise on behavioral, morphological and epigenetic changes in the offspring of immune-challenged mothers
• Grantee: Jansen Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/03368-5 - Effects of exercise-induced increases in brain uptake of serum IGF-1 on raphe nuclei-hippocampal circuitry: implication on adult neurogenesis and mood homeostasis.
• Grantee: Jansen Fernandes
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor