Open AccessIGF1R signaling regulates astrocyte-mediated neurovascular coupling in mice: implications for brain aging
Author(s) -
Stefano Tarantini,
Priya Balasubramanian,
Andriy Yabluchanskiy,
Nicole M. Ashpole,
Sreemathi Logan,
Tamás Kiss,
Anna Ungvari,
Ádám NyúlTóth,
Michal Laniado Schwartzman,
Zoltán Benyó,
William E. Sonntag,
Anna Csiszár,
Zoltán Ungvári
Publication year - 2021
Publication title -
geroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.883
H-Index - 63
eISSN - 2509-2715
pISSN - 2509-2723
DOI - 10.1007/s11357-021-00350-0
Subject(s) - astrocyte , downregulation and upregulation , neuroscience , insulin like growth factor 1 receptor , medicine , endocrinology , neurovascular bundle , signal transduction , receptor , chemistry , biology , microbiology and biotechnology , growth factor , pathology , central nervous system , biochemistry , gene
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.