STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior

Scientific Reports
Eryan KongDaniela D Pollak

Abstract

Experimental evidence suggests a role for the immune system in the pathophysiology of depression. A specific involvement of the proinflammatory cytokine interleukin 6 (IL6) in both, patients suffering from the disease and pertinent animal models, has been proposed. However, it is not clear how IL6 impinges on neurotransmission and thus contributes to depression. Here we tested the hypothesis that IL6-induced modulation of serotonergic neurotransmission through the STAT3 signaling pathway contributes to the role of IL6 in depression. Addition of IL6 to JAR cells, endogenously expressing SERT, reduced SERT activity and downregulated SERT mRNA and protein levels. Similarly, SERT expression was reduced upon IL6 treatment in the mouse hippocampus. Conversely, hippocampal tissue of IL6-KO mice contained elevated levels of SERT and IL6-KO mice displayed a reduction in depression-like behavior and blunted response to acute antidepressant treatment. STAT3 IL6-dependently associated with the SERT promoter and inhibition of STAT3 blocked the effect of IL6 in-vitro and modulated depression-like behavior in-vivo. These observations demonstrate that IL6 directly controls SERT levels and consequently serotonin reuptake and identify STAT3-depe...Continue Reading

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Citations

Nov 7, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Qian LiQiyong Gong
Dec 24, 2015·Medicine and Science in Sports and Exercise·Inga Bae-GartzEva Hucklenbruch-Rother
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Apr 19, 2017·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Łukasz ZadkaMarcin Olajossy
Jan 12, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Mohamed Saleem Abdul ShukkoorSharida Fakurazi
Nov 6, 2018·Development, Growth & Differentiation·Jun KitanoMakoto Kusakabe
May 10, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sun-Ho KwonSang-Kyu Ye
Feb 28, 2019·Frontiers in Neuroscience·Anne BaudryBenoit Schneider
Jul 28, 2016·Scientific Reports·Yong SunXiangdong Deng
Feb 18, 2021·Journal of Neuroinflammation·Elnaz RoohiFarshad Hashemian
Aug 8, 2021·International Journal of Molecular Sciences·Ning LiuXiaoyu Wang
Mar 16, 2017·ACS Chemical Neuroscience·Md Sharif ShajibWaliul I Khan
Sep 3, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sabah HaqWaliul I Khan

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Methods Mentioned

BETA
immunoprecipitation
immunoprecipitation assay
immunoprecipitations

Software Mentioned

BioStat
VIDEOTRACK PORSOLT

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