Methionine choline reverses lead-induced cognitive and N-methyl-d-aspartate receptor subunit 1 deficits

The principal effects of Pb2+ exposure in children are attention, memory and learning deficits that persist into adulthood. The application of the conventional chelators in children is somewhat prohibited by adverse health effects and is not effective in reversing learning deficits once they have occurred. In this study, we applied the nutrients, methionine and choline, to prevent Pb2+-induced cognitive impairment. Male weanling Sprague–Dawley rats were divided into five groups. Three groups of rats were exposed to Pb2+ in drinking water containing 400 mg/L Pb2+ acetate, of which two groups were concurrently administered by oral gavage once a day, 6 days per week, with low or high doses of methionine and choline for 60 days. The normal control group received distilled water alone, and the reagent control received methionine choline chloride alone. Methionine choline treatment reversed long-term deficits in spatial learning and memory caused by Pb2+ exposure in rats. Enhanced learning performance of Pb2+-exposed rats was associated with recovery of deficits in N-methyl-d-aspartate receptor (NMDAR) subunit 1 (NR1) mRNA and protein expression in the hippocampus. The effect of methionine choline on NR1 gene and protein expression was somewhat specific to Pb2+-exposed rats and did not affect the NR2A and NR2B subunits of the NMDAR measured in the same animals. Moreover, methionine choline treatment did not lower brain Pb2+ content in Pb2+-exposed rats, although it reduced blood and bone Pb2+ content. Methionine and choline reversed cognitive and NR1 deficits induced by Pb2+ exposure, a beneficial effect that has significant clinical implications for the treatment of childhood Pb2+ intoxication.