Neurotoxicological Effects of Low-Dose Methylmercury and Mercuric Chloride in Developing Offspring Mice

Mercury is a well-known toxic metal and potently induces severe neurotoxicological effects, especially in infants and children. The purpose of this study was to explore the underlying mechanisms of neurotoxic effects of mercurial compounds on the different stages of developing mice. Low- doses the probability of human exposure in mercury- contaminated areas of methylmercury MeHg M. 0.02 mg/kg/day and mercury chloride HgCl2 H, 0.5 mg/kg/day were administered to mice of the following groups: 1 treatment with distilled water for 7 consecutive weeks after weaning control-vehicle CV; exposure to mercurial compounds at different stages; 2 for 7 consecutive weeks after weaning control-MeHg CM and control-HgCl2 CH; 3 only during perinatal and weaning stages MeHg-vehicle MV and HgCl- vehicle HV; and 4 in all experimental stages MeHg-MeHg MM and HgCl2-HgCl2 HH. Results revealed the neurobehavioral defects increased locomotor activities, motor equilibrium impairment, and auditory dysfunction that correlated with increasing Hg accumulation in CM and CH groups. However, it revealed a decrease and an increase in locomotor activities in MV and HV groups, respectively; these became more severe in MM and HH groups than in MV and HV groups. Motor equilibrium performance in MV and HV groups remained normal, while that in MM and HH groups was decreased. The most severe auditory defects altered auditory brainstem response. ABR test found in MM and HH groups than those in the respective CM and CH, MV and HV, including absolute wave III delays and interwave I- III latencies, which suggested that the irreversible auditory dysfunction caused by mercurial compounds. Furthermore, the alteration of lipid peroxidation LPO. Na+/K+-ATPase activities, and nitric oxide NOx in the brain tissues contributed to the observed neurobehavioral dysfunction and hearing impairment. These findings provide evidence that fetuses were much more susceptible to the effects of mercurial compounds with regard to inducing severely neurotoxicological injuries as that found in human beings. The signaling of ROS/Na+-K+-ATPase/NOx plays a crucial role in the underlying mechanism for mercurial compound-induced toxic effects in offspring