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<p>Benzo[a]pyrene (B[a]P), an environmental neurotoxin, induces cognitive decline through ferroptosis-mediated mechanisms. Transcriptomic analysis (GSE75206) of B[a]P-exposed mouse hippocampus identified 1668 differentially expressed genes, with <i>Plin4</i> emerging as a key regulator linked to ferroptosis and lipid droplet (LD) accumulation. Behavioral tests confirmed hippocampal-dependent cognitive impairment and <i>Plin4</i> upregulation. Molecular analyses demonstrated ferroptosis activation, evidenced by altered expression of related genes (<i>Gpx4</i>, <i>Slc7a11</i>, <i>Ptgs2</i>) and biochemical markers of lipid peroxidation and iron imbalance. In HT22 cells, Benzopyrene-7,8-Diol-9,10-Epoxide (BPDE) dose-dependently elevated <i>Plin4</i> expression, inducing mitochondrial damage and ferroptosis. Silencing <i>Plin4</i> reversed BPDE-induced ferroptosis by restoring redox balance, reducing LD accumulation, and improving mitochondrial integrity. Mechanistically, <i>Plin4</i> amplifies B[a]P neurotoxicity by exacerbating iron overload and LD accumulation, sensitizing neurons to ferroptosis. This study identifies <i>Plin4</i> as a central mediator of environmental pollutant-induced neurodegeneration and proposes it as a therapeutic target for ferroptosis-related cognitive disorders.</p>

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Plin4 modulates lipid droplet accumulation and ferroptosis in neurons exposed to benzo[a]pyrene

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Hongyu Sun,
  • Zhirui Ma,
  • Xingdi Guo,
  • Jie Chen,
  • Hui He,
  • Xiaomin Tong,
  • Tingyu Ji,
  • Shihan Ding,
  • Chaoli Zhou,
  • Yi Lyu,
  • Fengjie Tian,
  • Jinping Zheng

摘要

Benzo[a]pyrene (B[a]P), an environmental neurotoxin, induces cognitive decline through ferroptosis-mediated mechanisms. Transcriptomic analysis (GSE75206) of B[a]P-exposed mouse hippocampus identified 1668 differentially expressed genes, with Plin4 emerging as a key regulator linked to ferroptosis and lipid droplet (LD) accumulation. Behavioral tests confirmed hippocampal-dependent cognitive impairment and Plin4 upregulation. Molecular analyses demonstrated ferroptosis activation, evidenced by altered expression of related genes (Gpx4, Slc7a11, Ptgs2) and biochemical markers of lipid peroxidation and iron imbalance. In HT22 cells, Benzopyrene-7,8-Diol-9,10-Epoxide (BPDE) dose-dependently elevated Plin4 expression, inducing mitochondrial damage and ferroptosis. Silencing Plin4 reversed BPDE-induced ferroptosis by restoring redox balance, reducing LD accumulation, and improving mitochondrial integrity. Mechanistically, Plin4 amplifies B[a]P neurotoxicity by exacerbating iron overload and LD accumulation, sensitizing neurons to ferroptosis. This study identifies Plin4 as a central mediator of environmental pollutant-induced neurodegeneration and proposes it as a therapeutic target for ferroptosis-related cognitive disorders.