Methamphetamine regulates microglial polarization and glycolytic activity to promote Parkinson's disease through the LIPH/LPA/PI3K/AKT signaling axis.

作者：Yanghong Zou, Chunhai Zhang, Hui Bian, Hao Fan, Ailan Pang, Yi Yuan, Jinghui Li, Xin Geng · 发表于：International Immunopharmacology · 年份：2026 · DOI：10.1016/j.intimp.2026.116306 · 被引用次数：1 · 研究领域：Medicine

BACKGROUND The abuse of methamphetamine (METH) is associated with an increased risk of Parkinson's disease (PD), whereas microglial polarization and glucose metabolism disorders are closely related to the progression of PD. This study aimed to investigate the specific molecular mechanism underlying the promotion of PD progression by METH through the regulation of microglial polarization and glycolysis. METHODS METH-induced C57BL/6 mice and BV2 cells were used to construct PD-like neurotoxicity animal and cell models for experimental investigation. Behavioral tests, immunohistochemistry and Nissl staining were used to assess the behavioral ability and neuronal damage of the animals. The levels of related proteins, inflammatory cytokines and glycolysis were detected using immunofluorescence, ELISA, Western blotting, and CCK-8 assays. RESULTS METH treatment significantly promoted behavioral disorders in PD mice, reduced the number of TH-positive neurons, and aggravated neuronal damage in the substantia nigra (SN). In addition, METH decreased the M2 marker proteins Arg-1 and CD206 and increased the M1 marker proteins iNOS and CD86; the proinflammatory cytokines TNF-α, IL-β, and IL-6; and glucose uptake, glucose consumption and lactic acid production, thus promoting M1 polarization and glycolytic activity in BV2 cells. In terms of the underlying molecular mechanism, METH treatment significantly increased the level of LPA. METH promotes LPA expression via upregulation of LIPH e...