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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

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

Author(s): Xiao Xue, Rui Duan, Qiao-Quan Zhang, Si-Yu Wang, Peng-Yu Gong, Yan E, Ying-Dong Zhang* and Teng Jiang*

Volume 18, Issue 3, 2021

Published on: 11 October, 2021

Page: [343 - 350] Pages: 8

DOI: 10.2174/1567202618666211012095210

Price: $65

Abstract

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-β (Aβ), 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 Aβ levels, and suppressing neuroinflammatory responses.

Conclusion: These findings indicate that MAS1-mediated signaling may represent a novel therapeutic target for CCH-related neurodegenerative diseases.

Keywords: Renin-angiotensin System, chronic cerebral hypoperfusion, synaptic degeneration, Ang-(1-7), AVE0991, neuroinflammation.

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