AUTHOR=Liu Jianhui , Ai Pu , Sun Yiyan , Yang Xiaoyu , Li Chunhong , Liu Yihan , Xia Xiaohuan , Zheng Jialin C. 

TITLE=Propofol Inhibits Microglial Activation via miR-106b/Pi3k/Akt Axis

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.768364

DOI=10.3389/fncel.2021.768364

ISSN=1662-5102

ABSTRACT=<p>Propofol is an established intravenous anesthetic agent with potential neuroprotective effects. In this study, we investigated the roles and the underlying mechanisms of propofol in inhibiting the pro-inflammatory responses of microglia. Propofol significantly reduced the messenger RNA (mRNA) levels of <italic>Tnf</italic>, <italic>Nos2</italic>, and NF-κB pathway related genes <italic>Ticam1</italic>, <italic>Myd88</italic>, <italic>Irf3</italic>, and <italic>Nfkb1</italic> in lipopolysaccharide (LPS)-treated primary microglia. After screening the miRNA profiles in microglia under LPS and propofol treatment conditions, we found propofol abrogated the LPS-induced misexpression of miRNAs including miR-106b, miR-124, miR-185, and miR-9. Perturbation of function approaches suggested miR-106b as the core miRNA that mediated the anti-inflammatory effects of propofol on microglial activation. RNA sequencing (RNA-seq) analysis further identified Pi3k/Akt signaling as one of the most affected pathways after miR-106b perturbation of function. The treatment of Pi3k/Akt signaling agonist 740Y-P elevated miR-106b-reduced Akt phosphorylation and abolished the inhibitory effects of miR-106b on the pro-inflammatory responses of microglia. Our results suggest propofol inhibits microglial activation <italic>via</italic> miR-106b/Pi3k/Akt axis, shedding light on a novel molecular mechanism of propofol-mediated immunomodulatory effects and implying propofol as potential therapeutics for treating neuroinflammation-related neurodegenerative diseases.</p>