Open AccessIGF ‐1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging
Author(s) -
Toth Peter,
Tarantini Stefano,
Ashpole Nicole M.,
Tucsek Zsuzsanna,
Milne Ginger L.,
ValcarcelAres Noa M.,
Menyhart Akos,
Farkas Eszter,
Sonntag William E.,
Csiszar Anna,
Ungvari Zoltan
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12372
Subject(s) - biology , cognitive decline , neurovascular bundle , endocrinology , medicine , neuroscience , dementia , anatomy , disease
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‐ AAV 8) 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.