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

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

  • Mol Psychiatry. 2026 Mar;31(3):1455-1474. doi: 10.1038/s41380-025-03260-1.
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

Affiliations

  • 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 2 Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 3 Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 4 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 5 Department of Hematology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 6 Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 7 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China. [email protected].
  • 8 Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China. [email protected].
  • 9 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. [email protected].
  • 10 Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, 430060, China. [email protected].
  • # Contributed equally.
PMID: 40954280 DOI: 10.1038/s41380-025-03260-1
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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