A Non-Peptidic MAS1 Agonist AVE0991 Alleviates Hippocampal Synaptic Degeneration in Rats with Chronic Cerebral Hypoperfusion

被引：6
作者：
Xue, Xiao [1 ]
Duan, Rui [1 ,2 ]
Zhang, Qiao-Quan [3 ]
Wang, Si-Yu [1 ]
Gong, Peng-Yu [1 ]
Yan, E. [1 ]
Zhang, Ying-Dong [1 ,2 ]
Jiang, Teng [1 ]
机构：
[1] Nanjing Med Univ, Nanjing Hosp 1, Dept Neurol, Nanjing 210006, Peoples R China
[2] China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Nanjing 211198, Peoples R China
[3] Nanjing Med Univ, Nanjing Brain Hosp, Dept Pathol, Nanjing 210029, Peoples R China
来源：
CURRENT NEUROVASCULAR RESEARCH | 2021年 / 18卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Renin-angiotensin System; chronic cerebral hypoperfusion; synaptic degeneration; Ang-(1-7); AVE0991; neuroin-flammation; A-BETA; ANGIOTENSIN-(1-7); INFLAMMATION; IMPAIRMENT; ACTIVATION; APOPTOSIS; AVE-0991; BRAIN;
D O I：
10.2174/1567202618666211012095210
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Background: Chronic cerebral hypoperfusion (CCH) is a contributing factor for neurodegenerative diseases. As a recently identified heptapeptide of the brain renin-angiotensin system, angiotensin-(1-7) has been revealed to activate its receptor MAS1 and thus ameliorated cognitive impairments in rats with CCH. Since hippocampal synaptic degeneration represents an important pathological basis of cognitive deficits, we hypothesize that activating MAS1-mediated signaling may alleviate CCH-induced synaptic degeneration in the hippocampus. Methods: In this study, we tested this hypothesis and uncovered the underlying mechanisms in a rat model of CCH induced by bilateral common carotid artery ligation surgery. At one week after the surgery, rats received a daily intraperitoneal vehicle injection or a non-peptidic MAS1 agonist AVE0991 for 8 weeks. During this procedure, Cerebral Blood Flow (CBF) was recorded. The levels of MAS1, amyloid-beta (A beta), neuroinflammatory cytokines, glial cell markers, and synaptophysin in the hippocampus were assessed at the end of the treatment period. Results: We showed that AVE0991 significantly alleviated hippocampal synaptic degeneration in rats with CCH. This protection might be achieved by facilitating CBF recovery, reducing hippocampal A beta levels, and suppressing neuroinflammatory responses. Conclusion: These findings indicate that MAS1-mediated signaling may represent a novel therapeutic target for CCH-related neurodegenerative diseases.
引用
收藏
页码：343 / 350
页数：8
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