Journal Article

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

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

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amygdala / Animals / Antiretroviral drugs / Antiretroviral therapy / Anxiety / Biomedical and Life Sciences / Biomedicine / Care and treatment / Cerebrospinal fluid / Chronic stress / Cyclic GMP-AMP synthase / Depression - drug therapy / Diagnosis / Diseases / Drug therapy / Emotional behavior / Emotions / Endogenous retrovirus / Endogenous Retroviruses / Gene expression / Gene regulation / Genetic aspects / Hypotheses / Immuno-inflammation / Immunology / Inflammasomes / Inflammation / Inflammation - metabolism / Information technology / Life sciences / Male / Medical innovations / Mental disorders / Mental illness / Mice / Mice, Inbred C57BL / Microglia / Microglia - metabolism / Neurobiology / Neurology / Neurosciences / NF-κB protein / p53 Protein / Proteins / Psychosis / Relapse / Signal Transduction / Stimulator of interferon genes / Stress / Stress, Psychological - psychology / Transcription / Transcription activation / Tumor necrosis factor-TNF