Abstract: Arsenic exposure is known to cause cognitive deficits, although the underlying mechanisms are yet to be explored. In this study, we investigated the role of nerve growth factor (NGF), a neuroprotective factor, in arsenic-induced cognitive impairment. In mouse models exposed to 25 and 50 mg/L sodium arsenite (NaAsO₂), we observed neuronal damage accompanied by the downregulation of NGF, decreased phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), reduced phosphorylation of the mitochondrial fission protein dynamin-related protein 1 (Drp1), and downregulation of the mitochondrial fusion protein optic atrophy 1 (OPA1). Similarly, the downregulation of NGF, inactivation of the PI3K/AKT signaling pathway, mitochondrial dynamics imbalance (dysregulation of mitochondrial fission and fusion processes), and increased apoptosis were observed in HT-22 cells exposed to 4 μmol/L NaAsO₂. NGF overexpression mitigated these arsenic-induced alterations, while the protective effect of NGF against arsenic toxicity was reduced by LY294002, a PI3K/AKT pathway inhibitor. These findings suggest that a decrease in NGF mediates the arsenic-disrupted mitochondrial dynamics via inhibiting the PI3K/AKT pathway, ultimately impairing cognitive function.

神经生长因子（NGF）下调介导砷暴露诱导的体内外线粒体动力学失衡与神经元损伤

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