Departments of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
The Neuro- Lab, Department of Human Anatomy, School of Basic Medical Sciences, Federal University of Technology Akure, Akure, Nigeria.
Environ Toxicol. 2022 Sep;37(9):2167-2177. doi: 10.1002/tox.23583. Epub 2022 May 21.
Manganese (Mn), although important for multiple cellular processes, has posed environmental health concerns due to its neurotoxic effects. In recent years, there have been extensive studies on the mechanism of Mn-induced neuropathology, as well as the sex-dependent vulnerability to its neurotoxic effects. Nonetheless, cellular mechanisms influenced by sex differences in susceptibility to Mn have yet to be adequately characterized. Since oxidative stress is a key mechanism of Mn neurotoxicity, here, we have probed Hsp70 and Nrf2 proteins to investigate the sex-dependent changes following exposure to Mn. Male and female rats were administered intraperitoneal injections of MnCl (10 mg/kg and 25 mg/kg) 48 hourly for a total of eight injections (15 days). We evaluated changes in body weight, as well as Mn accumulation, Nrf2 and Hsp70 expression across four brain regions; striatum, cortex, hippocampus and cerebellum in both sexes. Our results showed sex-specific changes in body-weight, specifically in males but not in females. Additionally, we noted sex-dependent accumulation of Mn in the brain, as well as in expression levels of Nrf2 and Hsp70 proteins. These findings revealed sex-dependent susceptibility to Mn-induced neurotoxicity corresponding to differential Mn accumulation, and expression of Hsp70 and Nrf2 across several brain regions.
锰（Mn）虽然对多种细胞过程很重要，但由于其神经毒性作用，对环境健康构成了威胁。近年来，人们对锰诱导的神经病理学机制以及对其神经毒性作用的性别依赖性易感性进行了广泛的研究。然而，受性别差异易感性影响的细胞机制尚未得到充分描述。由于氧化应激是锰神经毒性的关键机制，因此，我们研究了热休克蛋白 70（Hsp70）和核因子红细胞 2 相关因子 2（Nrf2）蛋白，以探讨暴露于锰后性别依赖性的变化。雄性和雌性大鼠每隔 48 小时腹膜内注射 MnCl2（10mg/kg 和 25mg/kg），共 8 次（15 天）。我们评估了体重变化以及 Nrf2 和 Hsp70 表达在两性四个脑区（纹状体、皮质、海马和小脑）的变化。结果显示，体重出现了性别特异性变化，仅在雄性中，而不在雌性中。此外，我们注意到大脑中锰的积累以及 Nrf2 和 Hsp70 蛋白表达存在性别依赖性。这些发现揭示了锰诱导的神经毒性的性别依赖性易感性，与锰在几个脑区的差异积累以及 Hsp70 和 Nrf2 的表达相对应。
