NYMC Faculty Publications
IGF1R Signaling Regulates Astrocyte-Mediated Neurovascular Coupling in Mice: Implications for Brain Aging
Author Type(s)
Faculty
Journal Title
Geroscience
First Page
901
Last Page
911
Document Type
Article
Publication Date
4-2021
Department
Pharmacology
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.
Recommended Citation
Tarantini, S., Balasubramanian, P., Yabluchanskiy, A., Ashpole, N. M., Logan, S., Kiss, T., Ungvari, A., Nyúl-Tóth, Á., Schwartzman, M. L., Benyo, Z., Sonntag, W. E., Csiszar, A., & Ungvari, Z. (2021). IGF1R Signaling Regulates Astrocyte-Mediated Neurovascular Coupling in Mice: Implications for Brain Aging. Geroscience, 43 (2), 901-911. https://doi.org/10.1007/s11357-021-00350-0
