AccScience Publishing / AN / Volume 1 / Issue 2 / DOI: 10.36922/an.v1i2.116

MicroRNA-195 rescues the impaired MS-dCA1 neural circuit and spatial memory in rats with chronic cerebral hypoperfusion

Xuqiao Wang1† Yi Xu1† Shuai Zhang1 Yang Qu1 Dongyang Wang1 Xiaobin An1 Lu Zeng1 Wentao Xu1 Yan Wu1 Haihui Chen1 Qin Wang1 Jing Ai1*
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1 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
Advanced Neurology 2022, 1(2), 116
Submitted: 30 May 2022 | Accepted: 9 August 2022 | Published: 30 August 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

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- 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 (I/O) curve, increased paired-pulse ratio (PPR), decreased numbers of ChAT+ and PV+ neurons in MS, and diminished theta rhythm in the hippocampus. More importantly, exogenously supplemented miR-195 into the MS region rescued the damaged neural circuit in MS-dCA1 of CCH rats by injecting lenti-pre-miR-195. Gain-of-function of miR-195 in the MS region significantly improved the cognitive dysfunction in CCH rats assessed by the Morris water maze test. In conclusion, knockdown of miR-195 in the MS region can impair MS-dCA1 neural circuit function, while upregulation of miR- 195 can rescue the impaired function of MS-dCA1 neural circuit and spatial memory ability in CCH rats. This provides a valuable reference for future anti-dementia therapy involving miR-195.

Chronic cerebral hypoperfusion
Medial septum-dorsal hippocampal CA1 neural circuit
National Science and Technology Innovation 2030 - Major program of “Brain Science and Brain-Like Research”
National Natural Science Foundation of China
Key Research and Development Program of Heilongjiang Province
Heilongjiang Touyan Innovation Team Program

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Conflict of interest
The authors declare that they have no conflicts of interest to report.
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Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing