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Publication : Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner.

First Author  González-Vila A Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  8175
PubMed ID  38071352 Mgi Jnum  J:343729
Mgi Id  MGI:7566744 Doi  10.1038/s41467-023-44039-8
Citation  Gonzalez-Vila A, et al. (2023) Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner. Nat Commun 14(1):8175
abstractText  Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity in female mice and food entrainment in male mice. Additionally, ablating the insulin receptor in hypothalamic astrocytes alters cyclic energy homeostasis differently in male and female mice. Remarkably, the mutants exhibit altered dopamine metabolism, and the pharmacological modulation of dopaminergic signaling partially restores distinct circadian traits in both male and female mutant mice. Our findings highlight the role of astrocytic insulin-dopaminergic signaling in conveying time-of-feeding or lighting cues to the astrocyte clock, thus governing circadian behavior in a sex-specific manner.
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