| First Author | Toth P | Year | 2015 |
| Journal | Aging Cell | Volume | 14 |
| Issue | 6 | Pages | 1034-44 |
| PubMed ID | 26172407 | Mgi Jnum | J:271719 |
| Mgi Id | MGI:6208664 | Doi | 10.1111/acel.12372 |
| Citation | Toth P, et al. (2015) IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging. Aging Cell 14(6):1034-44 |
| abstractText | Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1(f/f) -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment. |
