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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
MicroRNA-195 rescues the impaired MS-dCA1

neural circuit and spatial memory in rats with
chronic cerebral hypoperfusion

Xuqiao Wang , Yi Xu , Shuai Zhang, Yang Qu, Dongyang Wang, Xiaobin An,
†
†
Lu Zeng, Wentao Xu, Yan Wu, Haihui Chen, Qin Wang, and Jing Ai*
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics
of China), College of Pharmacy of Harbin Medical University, Harbin, Heilongjiang Province, 150086,
China

Abstract

Chronic cerebral hypoperfusion (CCH) is a common risk factor for vascular dementia
and Alzheimer’s disease (AD). The previous studies have shown that CCH-induced
multiple AD-like pathological changes in the hippocampus and cortex through
downregulating the microRNA-195 (miR-195) expression. However, whether and
how miR-195 participates in the dysfunction of the medial septum (MS)-dorsal
hippocampal CA1 (dCA1) neural circuit following CCH is still obscure. In the present
study, we found that miR-195 was downregulated in the MS region of CCH rats.
Moreover, using electrophysiological recording and immunofluorescence staining
technique, we found that the knockdown of miR-195 through the injection of lenti-
† These authors contributed equally
to this work. AMO-195 into the MS region led to a pathological change that mimicked the damage
to the MS-dCA1 neural circuit in CCH rats, including the decreased input-output
*Corresponding author: (I/O) curve, increased paired-pulse ratio (PPR), decreased numbers of ChAT and PV
+
+
Jing Ai (aijing@ems.hrbmu.edu.cn;
azhrbmu@126.com) neurons in MS, and diminished theta rhythm in the hippocampus. More importantly,
exogenously supplemented miR-195 into the MS region rescued the damaged neural
Citation: Wang X, Xu Y, Zhang S,
et al., 2022 MicroRNA-195 rescues circuit in MS-dCA1 of CCH rats by injecting lenti-pre-miR-195. Gain-of-function of
the impaired MS-dCA1 neural circuit miR-195 in the MS region significantly improved the cognitive dysfunction in CCH
and spatial memory in rats with rats assessed by the Morris water maze test. In conclusion, knockdown of miR-195 in
chronic cerebral hypoperfusion. Adv
Neuro, 1(2): 116. the MS region can impair MS-dCA1 neural circuit function, while upregulation of miR-
https://doi.org/10.36922/an.v1i2.116 195 can rescue the impaired function of MS-dCA1 neural circuit and spatial memory
Received: May 30, 2022 ability in CCH rats. This provides a valuable reference for future anti-dementia therapy
involving miR-195.
Accepted: August 9, 2022
Published Online: August 30, 2022
Keywords: Chronic cerebral hypoperfusion; MicroRNA-195; Medial septum-dorsal
Copyright: © 2022 Author(s). hippocampal CA1 neural circuit
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. With the increasing incidence of cerebrovascular diseases and the aggravation of
Publisher’s Note: AccScience population aging, vascular dementia (VaD) has become the most common type of
Publishing remains neutral with dementia after Alzheimer’s disease (AD) . VaD is a clinical syndrome of cognitive decline
[1]
regard to jurisdictional claims in
published maps and institutional caused by cerebral hypoperfusion due to various ischemic or hemorrhagic cerebrovascular
affiliations. diseases . It is well known that chronic cerebral hypoperfusion (CCH), which usually
[2]
Volume 1 Issue 2 (2022) 1 https://doi.org/10.36922/an.v1i2.116