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Open Access 01-12-2023 | Retrovirus | Research

Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress

Authors: Han Bao, Jinqi Yan, Jiancheng Huang, Wenjuan Deng, Ce Zhang, Cong Liu, Ailing Huang, Qiao Zhang, Ying Xiong, Qiang Wang, Huanghui Wu, Lichao Hou

Published in: Journal of Neuroinflammation | Issue 1/2023

Abstract

Background

The “missing” link of complex and multifaceted interplay among endogenous retroviruses (ERVs) transcription, chronic immuno-inflammation, and the development of psychiatric disorders is still far from being completely clarified. The present study was aimed to investigate the mechanism of protective role of inhibiting ERVs on reversing microglial immuno-inflammation in basolateral amygdala (BLA) in chronic stress-induced negative emotional behaviors in mice.

Methods

Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 6 w. Negative emotional behaviors were comprehensively investigated to identify the susceptible mice. Microglial morphology, ERVs transcription, intrinsic nucleic acids sensing response, and immuno-inflammation in BLA were assessed.

Results

Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors, and accompanied with significant microglial morphological activation, murine ERVs genes MuERV-L, MusD, and IAP transcription, cGAS–IFI16–STING pathway activation, NF-κB signaling pathway priming, as well as NLRP3 inflammasome activation in BLA. Antiretroviral therapy, pharmacological inhibition of reverse transcriptases, as well as knocking-down the ERVs transcriptional regulation gene p53 significantly inhibited microglial ERVs transcription and immuno-inflammation in BLA, as well as improved the chronic stress-induced negative emotional behaviors.

Conclusions

Our results provided an innovative therapeutic approach that targeting ERVs-associated microglial immuno-inflammation may be beneficial to the patients with psychotic disorders.

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Title: Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress
Authors: Han Bao
Jinqi Yan
Jiancheng Huang
Wenjuan Deng
Ce Zhang
Cong Liu
Ailing Huang
Qiao Zhang
Ying Xiong
Qiang Wang
Huanghui Wu
Lichao Hou
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Retrovirus
Interferon
Published in: Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-023-02724-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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