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Interaction of obesity and Nrf2 deficiency accelerates cerebromicrovascular aging and impairs neurovascular coupling responses
Author(s) -
ValcarcelAres Marta Noa,
Tarantini Stefano,
Hertelendy Peter,
Tucsek Zsuzsanna,
Gautam Tripti,
Kiss Tamas,
De Cabo Rafael,
Farkas Eszter,
Kinter Micheal,
Sonntag William E.,
Csiszar Anna,
Ungvari Zoltan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.681.5
Subject(s) - neurovascular bundle , oxidative stress , medicine , endocrinology , endothelial dysfunction , endothelium , neuroscience , biology , anatomy
Moment‐to‐moment adjustment of cerebral blood flow (CBF) via neurovascular coupling has a critical role in maintenance of healthy cognitive function. Previous studies demonstrate that obesity promotes cognitive impairment due to, at least in part, its deleterious effects on neurovascular coupling. Importantly, the effects of obesity are exacerbated in aging, but the underlying mechanisms remain elusive. There is increasing evidence that Nrf2/ARE signaling plays a critical role in vascular resilience to obesity and the metabolic syndrome and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular oxidative stress. The present study was designed to test the hypothesis that Nrf2 deficiency contributes to neurovascular uncoupling and exacerbate cerebromicrovascular dysfunction induced by obesity. To test this hypothesis Nrf2+/+ and Nrf2−/− mice were fed a standard diet or an adipogenic high fat diet (HFD) and cortical neurovascular coupling responses were assessed. In control mice feeding HFD for 6 months significantly increased vascular oxidative stress and decreased endothelium‐mediated CBF responses (laser Doppler flowmetry) in the somatosensory cortex evoked by contralateral whisker stimulation. Nrf2 deficiency significantly exacerbated HFD‐induced neurovascular uncoupling, mimicking the aging phenotype. Together, these results provide additional evidence that intact Nrf2 signaling importantly contributes to cerebromicrovascular health, preserving neurovascular coupling mechanisms. Further studies are needed to elucidate the endothelial and astrocytic mechanisms impacted by Nrf2 deficiency and HFD‐induced obesity, determining the potential roles of oxidative stress and chronic low‐grade neuroinflammation. Support or Funding Information This work was supported by grants from the American Heart Association, the National Center for Complementary and Alternative Medicine, and the National Institute on Aging