The brainstem as a target of developmental methylmercury toxicity

Rodent experiments have documented neuropathological lesions specifically located in the brainstem when toxic methylmercury (MeHg) exposure occurs at a particular time during brain development. The possible sensitivity of the brainstem to MeHg was explored in the prospective study of a Faroese birth cohort (N = 1,022), most recently examined at age 14 years. In 878 of eligible children (87%), latencies of BAEP peaks I, III, and V at 20 and 40 Hz were recorded, as was heart rate variability (HRV) and its frequency components of autonomic origin. Mercury concentrations were available from analyses of cord blood and maternal hair at birth, and in the child's hair at ages 7 and 14. Latencies of peaks III and V increased at higher cord-blood mercury concentrations. At both age 7 and 14 years, this effect appeared mainly within the I-III interpeak interval (i.e. in the signal transmission to the pons). In regard to heart rate variability, increased methylmercury exposure was associated with decreases in the coefficient of variation of the R-R interval. The low-frequency component of this variability was significantly associated with increased latency of BAEP peak III, but adjustment for methylmercury exposure substantially attenuated this correlation. The persistence of prolonged I-III interpeak intervals and of decreased autonomic activation of the heart rate indicates that some neurotoxic effects from intrauterine methylmercury exposure are irreversible. Parallel exposure-related delays of BAEP latencies may be due to underlying MeHG neurotoxicity to brainstem nuclei. This suggests a neurotoxic mechanism involved in cardiovascular abnormalities and increased mortalities related to dietary MeHg exposure.