Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice

Scientific Reports
Xiao ZhengHaiping Hao

Abstract

The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as t...Continue Reading

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Citations

Nov 24, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·Can JinDan-Shen Zhang
Dec 1, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiaojie ZangHaiping Hao
Jan 24, 2018·Behavioural Neurology·Chandran RamakrishnaEdouard M Cantin
Apr 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Weijie XieXiaobo Sun
Jun 14, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Caroline MénardScott J Russo
Sep 4, 2018·Frontiers in Neuroscience·Eva M Medina-RodriguezEléonore Beurel
Jul 31, 2018·Frontiers in Behavioral Neuroscience·Oliver AmbréeJudith Alferink
Oct 1, 2019·Annual Review of Psychology·Joana S Cruz-PereiraJohn F Cryan
Jan 29, 2019·Frontiers in Psychiatry·Carsten CulmseeJudith Alferink
Mar 12, 2021·Brain, Behavior, and Immunity·Marcel van de WouwJohn F Cryan
Jun 18, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zheng MouJun-Tian Zhang
Sep 8, 2021·Experimental & Molecular Medicine·Sherry Sin-Hang YeungRaymond Chuen-Chung Chang

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Methods Mentioned

BETA
PCR
proteomic profiling
flow cytometry
ELISA

Software Mentioned

EthoVision

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