Dexmedetomidine mitigates neuroinflammation in an Alzheimer's disease mouse model via the miR-204-3p/FBXL7 signaling axis.

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by neuroinflammation. Dexmedetomidine (Dex) is known for its neuroprotective properties in clinical settings. In this study, we investigated the potential of Dex in protecting against neuroinflammation in an AD mouse model induced by amyloid-beta (Aβ) injection. First, in the AD mouse model, Aβ injection were administered, and the model was confirmed through behavioral tests, including the Morris water maze and Y-maze. Neuroinflammatory states in Aβ-injected mice were assessed using hematoxylin and eosin staining and enzyme-linked immunosorbent assay. Expression levels of microRNA (miR)-204-3p and F-box/LRR-repeat protein 7 (FBXL7) in mouse tissues were determined through real-time quantitative polymerase chain reaction and Western blot. The binding interaction between miR-204-3p and FBXL7 was elucidated using dual-luciferase analysis. Aβ-injected mice exhibited cognitive impairment, neuroinflammation, and downregulated miR-204-3p. Upregulation of miR-204-3p reduced inflammatory infiltration and mitigated neuroinflammation in Aβ-injected mice. Dex treatment reduced inflammation in hippocampal tissues of Aβ-injected mice. Dex treatment upregulated miR-204-3p, leading to suppressed FBXL7 expression in tissues. Inhibition of miR-204-3p or overexpression of FBXL7 reversed the alleviating effect of Dex on neuroinflammation in Aβ-injected mice. Overall, Dex increased miR-204-3p expression, resulting in the inhibition of FBXL7, and subsequently alleviated neuroinflammation in Aβ-injected mice.

• Authors: Xia Lian, Xiaomin Zhang, Wenchao Chen, Fang Xue, Gaiqing Wang
• Journal: Brain research (Brain Res) Vol. 1822 Pg. 148612 (Sep 30 2023) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 37778649 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.