Sakamoto Mineshi, Kakita Akiyoshi, de Oliveira Ricardo Bezerra, Sheng Pan Huan, Takahashi Hitoshi
Department of Epidemiology, National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008, Japan.
Brain Res Dev Brain Res. 2004 Sep 17;152(2):171-6. doi: 10.1016/j.devbrainres.2004.06.016.
Rapid brain growth occurs primarily during the third trimester in humans, whereas in rats it occurs after parturition. Therefore, we hypothesized that the effects of methylmercury (MeHg) on the postnatal developing rat nervous system may help in understanding the neurotoxicity on the human fetal brain when the brain is most vulnerable. In the present experiment, the dose-response effects of MeHg treatment during the postnatal developing phase in rats were studied. Male Wistar rats were orally administered 0, 1, 3, and 5 mg/kg/day methylmercury chloride (MMC), respectively, on postnatal day 1 and for 30 consecutive days. The body weight decline began from day 25 and typical symptoms, such as hind-limb crossing and ataxia, were observed in rats treated with 5 mg/kg/day MMC. The weight loss and typical symptoms were not observed in rats treated with 1 and 3 mg/kg/day. Mercury (Hg) concentrations in the brain were 2.6, 4.5, and 9.6 microg/g in the rats treated with 1, 3, and 5 mg/kg/day, respectively, on the day after the final MMC treatment. At 5 to 6 weeks of age, dose-dependent deficits of motor coordination in the rotarod test and learning disability in the passive avoidance response test were observed. Histopathological examination of a proportion of the MeHg-treated rats revealed widespread neuronal degeneration manifested by neuron loss and astrocytosis in the cerebral cortex, striatum, and cerebellum, where severity of the lesions seemed to increase in proportion to the administered dose of MMC. These findings using neonatal rats will be useful for better understanding of the effects of MeHg in the developing human brain during gestation.
人类大脑的快速生长主要发生在妊娠晚期，而大鼠的大脑快速生长则发生在分娩后。因此，我们推测甲基汞（MeHg）对出生后发育中的大鼠神经系统的影响，可能有助于理解在人类胎儿大脑最脆弱时甲基汞对其产生的神经毒性。在本实验中，我们研究了MeHg在大鼠出生后发育阶段的剂量反应效应。雄性Wistar大鼠在出生后第1天分别口服给予0、1、3和5 mg/kg/天的氯化甲基汞（MMC），并连续给药30天。体重下降从第25天开始，在给予5 mg/kg/天MMC的大鼠中观察到典型症状，如后肢交叉和共济失调。给予1和3 mg/kg/天的大鼠未观察到体重减轻和典型症状。在最后一次MMC治疗后的第二天，给予1、3和5 mg/kg/天的大鼠大脑中的汞（Hg）浓度分别为2.6、4.5和9.6微克/克。在5至6周龄时，在转棒试验中观察到运动协调能力的剂量依赖性缺陷，在被动回避反应试验中观察到学习障碍。对一部分经MeHg处理的大鼠进行组织病理学检查，发现广泛的神经元变性，表现为大脑皮层、纹状体和小脑中的神经元丢失和星形细胞增多，病变的严重程度似乎与MMC的给药剂量成正比。这些使用新生大鼠的研究结果将有助于更好地理解妊娠期甲基汞对发育中的人类大脑的影响。
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