IGF1R signaling regulates astrocyte-mediated neurovascular coupling in mice: implications for brain aging

Autor: Michal L. Schwartzman, Priya Balasubramanian, Anna Csiszar, Ádám Nyúl-Tóth, Tamas Kiss, Anna Ungvari, Stefano Tarantini, Nicole M. Ashpole, Zoltan Ungvari, Zoltán Benyó, Andriy Yabluchanskiy, Sreemathi Logan, William E. Sonntag
Rok vydání: 2021
Předmět:
Zdroj: GeroScience
ISSN: 2509-2715
DOI: 10.1007/s11357-021-00350-0
Popis: Aging is associated with a significant deficiency in circulating insulin-like growth factor-1 (IGF-1), which has an important role in the pathogenesis of age-related vascular cognitive impairment (VCI). Impairment of moment-to-moment adjustment of regional cerebral blood flow via neurovascular coupling (NVC) importantly contributes to VCI. Previous studies established a causal link between circulating IGF-1 deficiency and neurovascular dysfunction. Release of vasodilator mediators from activated astrocytes plays a key role in NVC. To determine the impact of impaired IGF-1 signaling on astrocytic function, astrocyte-mediated NVC responses were studied in a novel mouse model of astrocyte-specific knockout of IGF1R (GFAP-Cre(ERT2)/Igf1r(f/f)) and accelerated neurovascular aging. We found that mice with disrupted astrocytic IGF1R signaling exhibit impaired NVC responses, decreased stimulated release of the vasodilator gliotransmitter epoxy-eicosatrienoic acids (EETs), and upregulation of soluble epoxy hydrolase (sEH), which metabolizes and inactivates EETs. Collectively, our findings provide additional evidence that IGF-1 promotes astrocyte health and maintains normal NVC, protecting cognitive health.
Databáze: OpenAIRE
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