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. 2025 Sep 16.
doi: 10.1038/s41380-025-03260-1. Online ahead of print.

Early-life inflammation increases aggressive behavior in adult male mice through an astrocyte-neuron signaling

Jiabei Wang #  1   2 , Jianhao Wang #  1   2 , Hongyu Chen #  1   2 , Feng Gao #  1   2 , Ruifeng Xu  1   2   3 , Yida Lv  1   2 , Shuai Ding  1   2 , Fang Li  1   2 , Xiang Li  1   2 , Yuke Shi  1   2 , Hangyu Wei  4 , Xinzhuo Chen  5 , Junqin Zhao  1   2 , Jing Xiong  1   2 , Xuejie Li  1   2   6 , Liang Zhao  3 , Qing-Tao Meng  7 , Xuan Xiao  8 , Zhi-Hao Wang  9   10
Affiliations

Early-life inflammation increases aggressive behavior in adult male mice through an astrocyte-neuron signaling

Jiabei Wang et al. Mol Psychiatry. .

Abstract

Accumulating research has demonstrated a significant association between early-life inflammation and behavioral disorders later in life. However, the effects of early-life inflammation on aggressive behavior in adulthood remain poorly understood. Here, we show that early-life inflammation induced by lipopolysaccharide (LPS) upregulated neuronal dynamin-related protein 1 (DRP1) and impaired mitochondrial function in medial prefrontal cortex (mPFC) of adult mice, thereby increasing aggressive behavior in adulthood. We further identify that CCAAT/enhancer binding protein β (C/EBPβ) is the transcription factor of Dnm1l, which was activated by an increased release of lysophosphatidic acid (LPA) induced by early-life inflammation. Moreover, the overproduction of LPA was due to a specific increase in astrocyte-secreted autotaxin (ATX). Specific knockdown of astrocytic ATX reduced early-life inflammation-induced aggression in wild-type mice, but not in Thy1-C/EBPβ transgenic mice. Remarkably, coenzyme Q10 decreased early-life inflammation-induced aggressive behavior in adult mice. Altogether, these findings provide new insights into the molecular mechanisms by which early inflammation promotes aggressive behavior in adulthood.

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Conflict of interest statement

Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethical approval: All animal experimental protocols were approved by the Laboratory Animal Welfare Ethical Committee of Renmin Hospital of Wuhan University (Approval No. WDRM 20250402A). Animal care and handling were conducted in accordance with the National Institutes of Health (NIH) animal care guidelines and the institutional guidelines of Wuhan University. Additionally, all procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Renmin Hospital of Wuhan University.

References

    1. Chaplin AB, Jones PB, Khandaker GM. Association between common early-childhood infection and subsequent depressive symptoms and psychotic experiences in adolescence: a population-based longitudinal birth cohort study. Psychol Med. 2020;52:1–11. - PubMed
    1. Dinel A-L, Joffre C, Trifilieff P, Aubert A, Foury A, Le Ruyet P, et al. Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood. J Neuroinflammation. 2014;11:155. - PubMed - PMC - DOI
    1. Gilmore JH, Jarskog LF. Exposure to infection and brain development: cytokines in the pathogenesis of schizophrenia. Schizophr Res. 1997;24:365–7. - PubMed - DOI
    1. Boksa P. Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav Immun. 2010;24:881–97. - PubMed - DOI
    1. Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron. 2020;107:234–56. - PubMed - PMC - DOI

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