Watanabe Jun, Nakamachi Tomoya, Ogawa Tetsuo, Naganuma Akira, Nakamura Masahisa, Shioda Seiji, Nakajo Sigeo
Department of Anatomy, School of Medicine, Showa University.
J Toxicol Sci. 2009 Jun;34(3):315-25. doi: 10.2131/jts.34.315.
Methylmercury (MeHg) is an environmental pollutant known to cause neurobehavioral defects and is especially toxic to the developing brain. With recent studies showing that fetal exposure to low-dose MeHg causes developmental abnormalities, it is therefore important to find ways to combat its effects as well as to clarify the mechanism(s) underlying MeHg toxicity. In the present study, the effects of MeHg on cultured neural progenitor cells (NPC) derived from mouse embryonic brain were investigated. We first confirmed the vulnerability of embryonic NPC to MeHg toxicity, NPC from the telencephalon were more sensitive to MeHg compared to those from the diencephalon. Buthionine sulfoximine (BSO) which is known to inhibit glutathione synthesis accelerated MeHg toxicity. Furthermore, antioxidants such as N-acetyl cysteine and alpha-tocopherol dramatically rescued the NPC from MeHg's toxic effects. Interestingly, a 12 hr delay in the addition of either antioxidant was still able to prevent the cells from undergoing cell death. Although it is now difficult to avoid MeHg exposure from our environment and contaminated foods, taking anti-oxidants from foods or supplements may prevent or diminish the toxicological effects of MeHg.
甲基汞（MeHg）是一种已知会导致神经行为缺陷的环境污染物，对发育中的大脑尤其有毒。最近的研究表明，胎儿暴露于低剂量的甲基汞会导致发育异常，因此，找到对抗其影响的方法并阐明甲基汞毒性的潜在机制很重要。在本研究中，研究了甲基汞对源自小鼠胚胎大脑的培养神经祖细胞（NPC）的影响。我们首先证实了胚胎神经祖细胞对甲基汞毒性的易感性，与来自间脑的神经祖细胞相比，端脑的神经祖细胞对甲基汞更敏感。已知能抑制谷胱甘肽合成的丁硫氨酸亚砜胺（BSO）会加速甲基汞的毒性。此外，抗氧化剂如N-乙酰半胱氨酸和α-生育酚能显著挽救神经祖细胞免受甲基汞的毒性影响。有趣的是，延迟12小时添加任何一种抗氧化剂仍能防止细胞死亡。虽然现在很难避免从我们的环境和受污染的食物中接触甲基汞，但从食物或补充剂中摄取抗氧化剂可能会预防或减少甲基汞的毒理学影响。
