Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There...

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Elmentve itt :
Bibliográfiai részletek
Szerzők: Tarantini Stefano
Valcarcel-Ares Marta Noa
Tóth Péter József
Yabluchanskiy Andriy
Zsuzsanna Tucsek
Kiss Tamás
Hertelendy Péter
Kinter Michael
Ballabh Praveen
Süle Zoltán
Farkas Eszter
Baur Joseph A.
Sinclair David A.
Csiszar Anna
Ungvári Zoltán István
Dokumentumtípus: Cikk
Megjelent: 2019
Sorozat:REDOX BIOLOGY 24
Tárgyszavak:
doi:10.1016/j.redox.2019.101192

mtmt:30646506
Online Access:http://publicatio.bibl.u-szeged.hu/25656
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520 3 |a Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI). 
650 4 |a Klinikai orvostan 
700 0 2 |a Valcarcel-Ares Marta Noa  |e aut 
700 0 2 |a Tóth Péter József  |e aut 
700 0 2 |a Yabluchanskiy Andriy  |e aut 
700 0 2 |a Zsuzsanna Tucsek  |e aut 
700 0 2 |a Kiss Tamás  |e aut 
700 0 2 |a Hertelendy Péter  |e aut 
700 0 2 |a Kinter Michael  |e aut 
700 0 2 |a Ballabh Praveen  |e aut 
700 0 2 |a Süle Zoltán  |e aut 
700 0 2 |a Farkas Eszter  |e aut 
700 0 2 |a Baur Joseph A.  |e aut 
700 0 2 |a Sinclair David A.  |e aut 
700 0 2 |a Csiszar Anna  |e aut 
700 0 2 |a Ungvári Zoltán István  |e aut 
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