Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them

作者：Alzahra J. Al Omran, Amy S. Shao, Saki Watanabe, Zeyu Zhang, Jifeng Zhang, Xue Chen, Junji Watanabe, Daryl L. Davies, Xuesi M. Shao, Jing Liang · 发表于：Journal of Neuroinflammation · 年份：2022 · DOI：10.1186/s12974-021-02368-9 · 被引用次数：81 · 研究领域：Medicinal plant effects and applications、Natural product bioactivities and synthesis、Biological Activity of Diterpenoids and Biflavonoids

BACKGROUND: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country's mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. METHODS: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. RESULTS: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivatio...