Electroacupuncture Improved Chronic Cerebral Hypoperfusion-Induced Anxiety-Like Behavior and Memory Impairments in Spontaneously Hypertensive Rats by Downregulating the ACE/Ang II/AT1R Axis and Upregulating the ACE2/Ang-(1-7)/MasR Axis.

Peipei Feng,Yafang Shen,Hao Liu,Zemin Wu,Xu Yao,Xinwei Li,Zui Shen

doi:10.1155/2020/9076042

Abstract

Electroacupuncture (EA) can effectively alleviate anxiety disorders and memory impairments caused by various neurodegenerative diseases; however, the molecular mechanisms underlying its neuroprotective effects are unclear. Previous studies have shown that the renin-angiotensin system (RAS) comprises of two axes with mutual antagonism: the classical angiotensin converting enzyme/angiotensin II/angiotensin II type 1 receptor (ACE/Ang II/AT1R) axis and the protective angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor (ACE2/Ang-(1-7)/MasR) axis. In this study, we observed that chronic cerebral hypoperfusion (CCH) mediated anxiety-like behavior and memory impairments in spontaneously hypertensive rats (SHR) via upregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and the partial hippocampal protective axis (ACE2/Ang-(1-7)). However, Ang II levels were much higher than those of Ang-(1–7), indicating that the ACE/Ang II/AT1R axis plays a dominant role in the comorbidity of CCH and hypertension. Moreover, candesartan cilexetil (Canc) and perindopril (Peril) were used as positive control drugs. We found that EA, Canc, and Peril attenuated CCH-induced anxiety-like behavior and memory impairments in SHR, potentially via downregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and upregulation of the whole hippocampal protective axis (ACE2/Ang-(1-7)/MasR). These results suggest that EA therapy for CCH with hypertension may be mediated by two hippocampal RAS axes.

Highlights

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological state of the central nervous system [1, 2]
On day 7, the right common carotid artery (2VO-R) was occluded; 1 week later, the left common carotid artery (2VO-L) was occluded using the same method. Following this preparation of the CCH model, the EA, candesartan cilexetil (Canc), and Peril interventions were initiated for 28 days (4 weeks)
The Open-Field Test (OFT) was performed on day 19, the Novel-Object Recognition Test (NORT) was performed on days 20−22, and the Morris Water Maze (MWM) test was performed on days 23−28

Summary

Introduction

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological state of the central nervous system [1, 2]. Longterm CCH can trigger neurodegeneration and eventually lead to progressive cognitive dysfunction [3,4,5]. Clinical research has shown that CCH is the common pathological foundation of Alzheimer’s disease, vascular dementia, vascular cognitive impairment, and other neurodegenerative diseases [6,7,8]. Understanding the mechanisms underlying CCH will facilitate the development of therapeutic strategies for the prevention and treatment of CCH-induced neurodegeneration [6]. The pathological and neuroprotective mechanisms of CCH are complicated. CCH is not an isolated pathophysiological phenomenon, but rather occurs alongside other vascular risk factors, including hypertension [10]. In order to better replicate the pathophysiology of human diseases, Neural Plasticity

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Conclusion