Dose-dependent effects of methylmercury administered during neonatal brain spurt in rats

Abstract

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 μg/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.