IGF‐1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging

Aging Cell

Peter Toth¹  Stefano Tarantini¹  Nicole M. Ashpole¹  Zsuzsanna Tucsek¹  Ginger L. Milne³  Noa M. Valcarcel-Ares¹  Akos Menyhart²  Eszter Farkas²  William E. Sonntag¹  Anna Csiszar¹ 

[1] Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA;Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary;Division of Clinical Pharmacology, Vanderbilt University Medical Center D-3100, Medical Center North, Nashville, TN, USA

关键词: arachidonic acid metabolites;    astrocyte;    endothelial dysfunction;    functional hyperemia;    Insulin‐like growth factor‐1;    neurovascular uncoupling;    nitric oxide;    somatomedin C;    vascular aging;    vascular cognitive impairment;   

DOI  :  10.1111/acel.12372

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.