NYMC Faculty Publications

IGF1R Signaling Regulates Astrocyte-Mediated Neurovascular Coupling in Mice: Implications for Brain Aging

Author Type(s)

Faculty

DOI

10.1007/s11357-021-00350-0

Journal Title

Geroscience

First Page

901

Last Page

911

Document Type

Article

Publication Date

4-2021

Department

Pharmacology

Keywords

Aging, Animals, Astrocytes, Brain, Cerebrovascular Circulation, Mice, Neurovascular Coupling

Disciplines

Medicine and Health Sciences

Abstract

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-CreERT2/Igf1rf/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.

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