Regulation of cerebral blood flow (CBF) to neuronal activity through neurovascular coupling (NVC) plays a critical role in maintaining healthy cognitive function.In aging, increased oxidative stress and cerebral microvascular endothelial dysfunction damage NVC, leading to cognitive decline.A growing body of evidence suggests that the decline in availability of NAD + with age plays a crucial role in a range of age-related cell damage, but its role in impaired NVC response remains to be explored.The purpose of this study was to test the hypothesis that the restoration of NAD + concentration might have a beneficial effect on the NVC response in aging.To test this hypothesis, nicotinamide mononucleotide (NMN), a key NAD + intermediate, was administered to 24-month-old C57BL / 6 mice for 2 weeks.NVC was assessed by measuring the CBF response to contralateral whisker stimulation (laser doppler flowmeter).We found that the NVC response was significantly impaired in senescent mice.
NMN supplements rescue the NVC response by increasing endothelial no-mediated vasodilation, which is associated with significant improvements in spatial working memory and gait coordination.These findings are related to the protective effect of NMN on sirtuin, which produces reactive oxygen species and mitochondrial bioenergy in mitochondria derived from cultured brain microvascular endothelial cells in older animals.Therefore, the decline in the utilization rate of NAD + will lead to age-related brain microvascular dysfunction, exacerbating cognitive decline.The protective effect of NMN on cerebral microvascular highlights the prevention and treatment potential of NAD + intermediates as an effective intervention for patients at risk of vascular cognitive impairment (VCI).