Open AccessNicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice
Author(s) -
Li ChengCheng,
Chen WeiXiang,
Wang Jie,
Xia Min,
Jia ZhengCai,
Guo Chao,
Tang XiaoQin,
Li MingXi,
Yin Yi,
Liu Xin,
Feng Hua
Publication year - 2020
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13276
Subject(s) - angiotensin ii , blood–brain barrier , white matter , neuroinflammation , pharmacology , vascular dementia , chemistry , medicine , endocrinology , central nervous system , disease , blood pressure , dementia , magnetic resonance imaging , radiology
Aims Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated. Methods To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. Results Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. Conclusion Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.