血管保护性
血管平滑肌
血管性痴呆
内科学
内分泌学
自动调节
医学
胰岛素样生长因子1受体
认知功能衰退
受体
神经科学
心理学
痴呆
血压
生长因子
平滑肌
疾病
一氧化氮
作者
Lauren R. Miller,Marisa A. Bickel,Stefano Tarantini,Megan E. Runion,Zoe Matacchiera,Mary Lee Vance,Cecily A. Hibbs,Hannah Vaden,Domonkos Nagykaldi,Teryn Martin,Elizabeth C. Bullen,J. Keith Pinckard,Tamás Kiss,Eric W. Howard,Andriy Yabluchanskiy,Shannon M. Conley
标识
DOI:10.3389/fnagi.2024.1320808
摘要
Introduction Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms, but the cellular mechanisms underlying IGF-1-deficiency associated pathologies in the aged cerebrovasculature remain poorly understood. Here, we test the hypothesis that vascular smooth muscle cells (VSMCs) play an integral part in mediating the vasoprotective effects of IGF-1. Methods We used a hypertension-based model of cerebrovascular dysfunction in mice with VSMC-specific IGF-1 receptor ( Igf1r ) deficiency and evaluated the development of cerebrovascular pathologies and cognitive dysfunction. Results VSMC-specific Igf1r deficiency led to impaired cerebral myogenic autoregulation, independent of blood pressure changes, which was also associated with impaired spatial learning and memory function as measured by radial arm water maze and impaired motor learning measured by rotarod. In contrast, VSMC-specific IGF-1 receptor knockdown did not lead to cerebral microvascular rarefaction. Discussion These studies suggest that VSMCs are key targets for IGF-1 in the context of cerebrovascular health, playing a role in vessel stability alongside other cells in the neurovascular unit, and that VSMC dysfunction in aging likely contributes to VCID.
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