The Innate Immune Receptors TLR2/4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation

Neuron
Xiang NieTomoyuki Furuyashiki

Abstract

Repeated environmental stress has been proposed to induce neural inflammation together with depression and anxiety. Innate immune receptors, such as Toll-like receptors (TLRs), are activated by exogenous or endogenous ligands to evoke inflammation. Here we show that the loss of TLR2 and TLR4 (TLR2/4) abolished repeated social defeat stress (R-SDS)-induced social avoidance and anxiety in mice. TLR2/4 deficiency mitigated R-SDS-induced neuronal response attenuation, dendritic atrophy, and microglial activation in the medial prefrontal cortex (mPFC). Furthermore, mPFC microglia-specific TLR2/4 knockdown blocked social avoidance. Transcriptome analyses revealed that R-SDS induced IL-1α and TNF-α in mPFC microglia in a TLR2/4-dependent manner, and antibody blockade of these cytokines in the mPFC suppressed R-SDS-induced social avoidance. These results identify TLR2/4 as crucial mediators of R-SDS-induced microglial activation in the mPFC, which leads to neuronal and behavioral changes through inflammation-related cytokines, highlighting unexpected pivotal roles of innate immunity in the mPFC in repeated environmental stress-induced behavioral changes. VIDEO ABSTRACT.

References

Nov 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Linda I PerrottiEric J Nestler
May 21, 2005·Atherosclerosis·Jane E MurphySreenivasan Ponnambalam
Jan 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ja Wook Koo, Ronald S Duman
Oct 17, 2008·Nature·Vaishnav Krishnan, Eric J Nestler
May 23, 2009·Nature Reviews. Immunology·Serge Rivest
Aug 1, 2009·Science·Eduardo Dias-FerreiraNuno Sousa
Jan 16, 2010·Science·Akiko Iwasaki, Ruslan Medzhitov
Apr 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eric S WohlebJohn F Sheridan
Jul 23, 2011·Science·Rosa C PaolicelliCornelius T Gross
Mar 24, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kohei TanakaShuh Narumiya
Oct 9, 2012·Science·Ronald S Duman, George K Aghajanian
Nov 28, 2012·Brain Structure & Function·Javier Gilabert-JuanJuan Nacher
Aug 24, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eric S WohlebJohn F Sheridan
Oct 29, 2013·Nature Neuroscience·Allison R Bialas, Beth Stevens
Dec 10, 2013·Nature Neuroscience·Oleg ButovskyHoward L Weiner
Apr 15, 2014·Nature Medicine·Kristie T OtaRonald S Duman
May 9, 2015·Nature Communications·Rosemary C BagotEric J Nestler
Dec 22, 2015·Cell·Samia HabbasAndrea Volterra
Jan 19, 2017·Nature·Shane A LiddelowBen A Barres

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Citations

Jan 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yasuhisa AnoKeiji Kondo
Feb 16, 2019·Neuropsychopharmacology Reports·Satoshi OkamuraTomoyuki Furuyashiki
May 6, 2019·Molecular Brain·Ruili DangMing-Gao Zhao
Jun 20, 2019·Psychiatry and Clinical Neurosciences·Tomoyuki Furuyashiki, Shiho Kitaoka
Nov 20, 2019·Brain and Behavior·Takashi KomoriToshifumi Kishimoto
Apr 12, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Ryota NakayamaTakuya Sasaki
May 23, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Caroline M SawickiJohn F Sheridan
Sep 18, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hikaru ItoHidenori Aizawa
Jul 15, 2020·The Journal of Pharmacology and Experimental Therapeutics·Alexandros G Kokkosis, Stella E Tsirka
Sep 29, 2020·Neural Regeneration Research·Yun-Wei FuChao-Ran Ren
Feb 28, 2019·International Immunology·Tomoyuki FuruyashikiShiho Kitaoka
Mar 7, 2020·EMBO Reports·Helena Caria Martins, Gerhard Schratt
Jul 19, 2020·Current Medical Science·Si-Long DengFang Wang
Jul 2, 2019·Biological & Pharmaceutical Bulletin·Takuya Sasaki
Sep 29, 2020·Neural Regeneration Research·Akitoshi OzakiGen Ohtsuki
Oct 18, 2020·Science China. Life Sciences·Xiaoning JiaHailan Hu
Nov 3, 2020·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Shiho Kitaoka
Sep 10, 2020·Journal of Neurochemistry·Luis A- Trujillo VillarrealAlberto Camacho-Morales
Feb 1, 2021·Brain, Behavior, and Immunity·A M HamiehF Marchand
Jan 12, 2021·Frontiers in Pharmacology·Ruyan Wu, Jun-Xu Li
Dec 23, 2020·International Journal of Molecular Sciences·Yasuhisa AnoTomoyuki Furuyashiki
Nov 15, 2020·Scientific Reports·Midori NagaiTomoyuki Furuyashiki
Mar 12, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Keitaro YoshidaKenji F Tanaka

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