Quercetin ameliorates memory impairment by inhibiting abnormal microglial activation in a mouse model of paradoxical sleep deprivation

Yangming Zhang; Yuqiao Xie; Zishuo Cheng; Kaiwen Xi; Xin Huang; Fang Kuang; Wenting Wang; Tiaotiao Liu; Baolin Guo; Shengxi Wu

doi:10.1016/j.bbrc.2022.09.088

Quercetin ameliorates memory impairment by inhibiting abnormal microglial activation in a mouse model of paradoxical sleep deprivation

Biochem Biophys Res Commun. 2022 Dec 3:632:10-16. doi: 10.1016/j.bbrc.2022.09.088. Epub 2022 Sep 27.

Authors

Affiliations

¹ Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
² School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, China.
³ Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: baolguo@fmmu.edu.cn.
⁴ Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: shengxi@fmmu.edu.cn.

PMID: 36191372
DOI: 10.1016/j.bbrc.2022.09.088

Abstract

Paradoxical sleep deprivation (PSD) is prevalent in modern society, and impaired memory is one of its serious consequences. The pathogenic mechanism is still unclear, and the therapeutic strategies for PSD are limited. Here, we found that quercetin treatment ameliorated memory impairments caused by PSD in a dose-dependent manner in an animal model. Quercetin could restore the dynamic changes of the gamma band while the animals performed novel object recognition (NOR) tasks as determined by electroencephalogram analysis. Morphological analysis showed that quercetin, by targeting the hippocampal CA1 region, strikingly ameliorated the overactivation of microglia induced by PSD. Mechanistically, quercetin inhibited the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-b (NF-κB) cascade, which is critical for abnormal microglial activation following PSD stress. Our results provided experimental evidence for the therapeutic effects of quercetin on PSD-related memory impairments by suppressing TLR4/MyD88/NF-κB signaling that mediated abnormal microglia activation in the hippocampus.

Keywords: Microglia; Neuroinflammation; Quercetin; Sleep deprivation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Memory Disorders* / drug therapy
Memory Disorders* / etiology
Mice
Microglia* / metabolism
Myeloid Differentiation Factor 88 / metabolism
NF-kappa B / metabolism
Quercetin* / pharmacology
Quercetin* / therapeutic use
Sleep, REM / drug effects
Toll-Like Receptor 4 / metabolism

Substances

Myeloid Differentiation Factor 88
NF-kappa B
Quercetin
Toll-Like Receptor 4