2. Academic Validation
  3. PPARγ in microglia helps protect adolescent male mice from harmful effects of stress during early development

PPARγ in microglia helps protect adolescent male mice from harmful effects of stress during early development

  • Brain Behav Immun. 2026 May:134:106483. doi: 10.1016/j.bbi.2026.106483.
Zhe Liu 1,  Jiutai Wang 2,  Yan Ge 3,  Yu Wang 4,  Hanyi Ling 5,  Yan Liu 1,  Jinqiang Zhang 6,  Zili You 7,  Yue Han 8
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, China.
  • 2 School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, China.
  • 3 Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
  • 4 Department of Rehabilitation Medicine, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 5 School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, China; College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310007, China.
  • 6 School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, China; Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China. Electronic address: [email protected].
  • 7 School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: [email protected].
  • 8 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, China; School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: [email protected].
PMID: 41672158 DOI: 10.1016/j.bbi.2026.106483
Abstract

Deficiency in the expression or activity of the nuclear hormone receptor Peroxisome Proliferator-activated Receptor γ (PPARγ) has been observed in autism spectrum disorder, bipolar disorder and Alzheimer's disease. Here we showed that separating mouse pups from their mothers for three hours daily during the first two weeks of life downregulated PPARγ, leading to pro-inflammatory polarization and activation of microglia in the hippocampus, which results in more severe responses to subsequent chronic restraint stress in adolescent Animals. These effects of maternal separation were reversed by activating PPARγ with pioglitazone at 30 mg/kg/day for one week, which also stimulated hippocampal neurogenesis. Knocking out PPARγ specifically in microglia reduced neural activity and dendritic spine density in the cortex and hippocampus and led to depressive-like behaviors in mice. These results suggest that PPARγ expression enables microglia to "remember" previous exposure to stress and thereby influence responses to future stress. The findings may help guide interventions against stress and related psychological disorders.

Keywords

Early life stress; Electrophysiology; Microglia; PPARγ; Synaptic plasticity.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.98%, PPARγ Antagonist