Regulating PPARG Reduces Lipid Accumulation in Microglia and Promotes Functional Recovery After Spinal Cord Injury

作者：Mingran Luo, Jiayun Liu, Yang Su, Tao Jiang, Xiajia Wu, Peng Gao, Tao Qin, Mengyuan Wu, Qingqing Li, Shujun Zhang, Baorong He, Yongxiang Wang, Xiaodong Guo, Wei Zhou, Shujie Zhao, Jin Fan, Jian Chen, Guoyong Yin · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202506313 · 被引用次数：11 · 研究领域：Spinal Cord Injury Research、Peroxisome Proliferator-Activated Receptors、Neuroinflammation and Neurodegeneration Mechanisms

Spinal cord injury (SCI) substantially affects functional capacity and the immune system plays a crucial role in recovery. Examining alterations in microglia metabolism can lead to improved repair mechanisms; however, the molecular subtyping of microglia lacks consensus. In this study, the effects of SCI on macrophages and microglia in mice are investigated to identify tailored therapeutic targets and interventions for patients with SCI. Macrophages infiltrate the spinal cord shortly after injury; however, infiltration decreases over time. Microglial phagocytosis of myelin debris is associated with increased lipid accumulation. Macrophage deletion improves outcomes, whereas microglial deletion worsens them. The PLIN2+ microglia subtype in lipid droplet formation shows abnormal activation of the Pparg signaling pathway compared with that with other subtypes. PPARG promotes lipid metabolism and recovery, and atorvastatin (a PPARG agonist) reverses altered metabolic processes. Macrophages and microglia play complex roles in SCI. Targeting PPARG and its agonists is a promising therapeutic approach for SCI.