Ferulic Acid Ameliorates Alzheimer's Disease-like Pathology and Repairs Cognitive Decline by Preventing Capillary Hypofunction in APP/PS1 Mice
Wang, NY; Li, JN; Liu, WL; Huang, Q; Li, WX; Tan, YH; Liu, F; Song, ZH; Wang, MY; Xie, N; Mao, RR; Gan, P; Ding, YQ; Zhang, Z; Shan, BC; Chen, LD; Zhou, QX; Xu, L
2021
发表期刊NEUROTHERAPEUTICS
ISSN1933-7213
卷号18期号:2页码:1064-1080
摘要Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of brain capillaries is triggered by beta-amyloid (A beta) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating A beta plaque deposition, the primary pathophysiology of Alzheimer's disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while A beta plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early A beta plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated A beta plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating A beta plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD.
收录类别sci
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/13529
专题科研部门_学习记忆的分子神经机制(徐林)
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Wang, NY,Li, JN,Liu, WL,et al. Ferulic Acid Ameliorates Alzheimer's Disease-like Pathology and Repairs Cognitive Decline by Preventing Capillary Hypofunction in APP/PS1 Mice[J]. NEUROTHERAPEUTICS,2021,18(2):1064-1080.
APA Wang, NY.,Li, JN.,Liu, WL.,Huang, Q.,Li, WX.,...&Xu, L.(2021).Ferulic Acid Ameliorates Alzheimer's Disease-like Pathology and Repairs Cognitive Decline by Preventing Capillary Hypofunction in APP/PS1 Mice.NEUROTHERAPEUTICS,18(2),1064-1080.
MLA Wang, NY,et al."Ferulic Acid Ameliorates Alzheimer's Disease-like Pathology and Repairs Cognitive Decline by Preventing Capillary Hypofunction in APP/PS1 Mice".NEUROTHERAPEUTICS 18.2(2021):1064-1080.
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