Rodier P M, Aschner M, Sager P R
Neurobehav Toxicol Teratol. 1984 Sep-Oct;6(5):379-85.
Methylmercury is toxic to both the mature and the developing nervous system. One mechanism of its effects on the developing neonatal cerebellum is its interference with cell production by mitotic arrest. To investigate whether this mechanism is active in the prenatal CNS, fetuses exposed to methylmercury were compared to control fetuses 24 hours or 48 hours after an 8 mg/kg dose to their dams. By the first sacrifice time, levels of Hg203 in fetuses approached the level in the dam, and by the second sacrifice time methylmercury-exposed fetuses weighed significantly less than controls. Four regions of the developing brain were studied to evaluate methylmercury effects on mitotic activity. General measures such as mitotic index, number of proliferative cells, and thickness of the proliferative zone were not reduced by treatment in any region at either sacrifice time. In contrast, each region showed evidence of methylmercury effects on the pattern of mitosis. Exposed fetuses had increased numbers of early mitotic figures, decreased numbers of late mitotic figures, or a decrease in the proportion of cells reaching late mitosis. Thus, neurons produced during gestation, like those produced postnatally, appear to be sensitive to methylmercury's antimitotic action. Whether the arrest of these cells leads to a permanent reduction in neuron number, as it does in neonates, remains to be investigated.
甲基汞对成熟和发育中的神经系统均有毒性。其对发育中的新生小脑产生影响的一种机制是通过有丝分裂停滞干扰细胞生成。为研究该机制在产前中枢神经系统中是否起作用，将给予母鼠8毫克/千克剂量甲基汞后24小时或48小时的暴露胎儿与对照胎儿进行比较。在第一次处死时，胎儿体内Hg203水平接近母鼠体内水平，到第二次处死时，暴露于甲基汞的胎儿体重明显低于对照组。对发育中大脑的四个区域进行研究以评估甲基汞对有丝分裂活性的影响。在任一处死时间，处理组均未使有丝分裂指数、增殖细胞数量和增殖区厚度等一般指标在任何区域降低。相反，每个区域均显示出甲基汞对有丝分裂模式有影响。暴露胎儿早期有丝分裂图像数量增加，晚期有丝分裂图像数量减少，或进入晚期有丝分裂的细胞比例降低。因此，孕期产生的神经元，与出生后产生的神经元一样，似乎对甲基汞的抗有丝分裂作用敏感。这些细胞的停滞是否会像在新生儿中那样导致神经元数量永久性减少，仍有待研究。
