Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China; Department of Planned Immunization, Xi'an Center for Disease Control and Prevention, No. 599 Xiying Road, Yanta District, Xi'an 710054, Shaanxi, China.
Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang 110122, Liaoning, China.
Neurotoxicol Teratol. 2023 Jan-Feb;95:107137. doi: 10.1016/j.ntt.2022.107137. Epub 2022 Nov 18.
Methylmercury (MeHg) is a potent neurotoxicant that could induce oxidative stress and autophagy. However, the underlying mechanisms through which MeHg affects the central nervous system have not been fully elucidated, and little has been known of the interaction between oxidative stress and autophagy. Therefore, rats were administrated with different MeHg concentrations to evaluate the neurotoxic effects and autophagy in cerebral cortex. Moreover, we have investigated the neuroprotective role of N-acetyl-L-cysteine (NAC) against MeHg-induced neurotoxicity in order to estimate the regulation effects of oxidative stress on autophagy. A total of 64 rats, 40 of which were randomly divided into control and MeHg-treated (4, 8 and 12 μ mol/kg) groups. The remaining 24 rats were divided into control, NAC control (1 mmol/kg), 12 μ mol/kg MeHg, and NAC pretreatment. Administration of 12 μ mol/kg MeHg significantly increased behavioral and pathological abnormalities, and autophagy levels. In addition, the oxidative stress levels increased, together with abnormal expression of autophagy-related molecules. Pretreatment with NAC significantly prevented MeHg-induced oxidative stress and PI3K/AKT/mTOR or AMPK/TSC2/mTOR-mediated autophagy. In conclusion, the present study suggested that oxidative stress can regulate autophagy through PI3K/AKT/mTOR or AMPK/TSC2/mTOR pathways. This study provides a theoretical basis for the study and treatment of MeHg-induced neurotoxicity.
甲基汞（MeHg）是一种强效的神经毒素，可诱导氧化应激和自噬。然而，甲基汞影响中枢神经系统的潜在机制尚未完全阐明，对于氧化应激与自噬之间的相互作用也知之甚少。因此，本研究采用不同浓度的甲基汞对大鼠进行处理，以评估其对皮质的神经毒性作用和自噬作用。此外，还研究了 N-乙酰-L-半胱氨酸（NAC）对甲基汞诱导的神经毒性的神经保护作用，以评估氧化应激对自噬的调节作用。共 64 只大鼠，其中 40 只随机分为对照组和甲基汞处理组（4、8 和 12 μmol/kg）。其余 24 只大鼠分为对照组、NAC 对照组（1 mmol/kg）、12 μmol/kg 甲基汞组和 NAC 预处理组。给予 12 μmol/kg 甲基汞后，大鼠的行为和病理异常以及自噬水平显著增加。此外，氧化应激水平升高，自噬相关分子表达异常。NAC 预处理可显著预防甲基汞诱导的氧化应激以及 PI3K/AKT/mTOR 或 AMPK/TSC2/mTOR 介导的自噬。综上所述，本研究表明氧化应激可通过 PI3K/AKT/mTOR 或 AMPK/TSC2/mTOR 途径调节自噬。本研究为研究和治疗甲基汞诱导的神经毒性提供了理论依据。
