@article{ref1,
title="The innate immune receptors TLR2/4 mediate repeated social defeat stress-induced social avoidance through prefrontal microglial activation",
journal="Neuron",
year="2018",
author="Nie, Xiang and Kitaoka, Shiho and Tanaka, Kohei and Segi-Nishida, Eri and Imoto, Yuki and Ogawa, Atsubumi and Nakano, Fumitake and Tomohiro, Ayaka and Nakayama, Kazuki and Taniguchi, Masayuki and Mimori-Kiyosue, Yuko and Kakizuka, Akira and Narumiya, Shuh and Furuyashiki, Tomoyuki",
volume="99",
number="3",
pages="464-479.e7",
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.<p /> <p>Language: en</p>",
language="en",
issn="0896-6273",
doi="10.1016/j.neuron.2018.06.035",
url="http://dx.doi.org/10.1016/j.neuron.2018.06.035"
}