Early-life inflammation increases aggressive behavior in adult male mice through an astrocyte-neuron signaling
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.
Authors
- Qingtao Meng (ORCID: https://orcid.org/0000-0002-1936-3050)
- Jiabei Wang (ORCID: https://orcid.org/0000-0002-4578-3817)
- Jing Xiong (ORCID: https://orcid.org/0000-0002-2221-5972)
- Wei Houren (ORCID: https://orcid.org/0000-0002-6467-7788)
- Liang Zhao (ORCID: https://orcid.org/0000-0002-3464-6956)
- Yonggang Lv (ORCID: https://orcid.org/0000-0003-3966-8975)
- Feng Gao (ORCID: https://orcid.org/0000-0002-7539-6455)
- Hongyu Chen (ORCID: https://orcid.org/0000-0002-5329-8854)
- Zhi-Hao Wang (ORCID: https://orcid.org/0000-0002-2517-8679)
- Xin Chen (ORCID: https://orcid.org/0000-0002-2628-4027)
- Xiang Li (ORCID: https://orcid.org/0000-0002-4855-0701)
- Xuejie Li (ORCID: https://orcid.org/0000-0001-9706-3435)
- Xuan Xiao (ORCID: https://orcid.org/0000-0001-7762-8689)
- Jianhao Wang (ORCID: https://orcid.org/0000-0002-4325-2860)
- Li Fang (ORCID: https://orcid.org/0009-0008-6436-8388)
- Yuke Shi
- Junqin Zhao
- Shuai Ding
- Ruifeng Xu
Institutions
- Anhui Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Wuhan University (CN)
- Renmin Hospital of Wuhan University (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
Publication Details
- Journal
- Molecular Psychiatry
- Published
- 2025-09-16
- DOI
- https://doi.org/10.1038/s41380-025-03260-1
- Primary Topic
- Tryptophan and brain disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Natural Science Foundation of Hubei Province
- Wuhan University
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences