REVERSIBILITY OF MANGANESE-INDUCED LEARNING DEFECT IN RATS

In this study the mechanism by which manganese (Mn) induces learning d efect and its reversibility has been investigated in rats. Female albi no rats were dosed orally with 357 mu g Mn/kg body weight for 15 or 30 days. Attempts were made to correct the Mn-induced learning defect by (1) co-administration of mevinolin and Mn for 30 days;(2) administrat ion of mevinolin for 15 days after 15 days of dosing with Mn, and (3) by withdrawal of Mn treatment (15 days dosing with Mn followed by 15 d ays without Mn). Mevinolin was given orally at 235.7 mu g/kg body weig ht. Significant increases in the Mn and cholesterol levels in the hipp ocampus were accompanied by an obvious slowness in learning of rats ex posed to Mn. After one training period (day 29) the time required to r each the exit of a T-maze was 104.5 +/- 13.8 sec for rats dosed with M n for 30 days, whereas that of the controls was 28.7 +/- 11.4 sec on d ay 30. This delay was completely corrected (to 30.7 +/- 6.0 sec) in ra ts co-administered mevinolin (an inhibitor of cholesterol biosynthesis ) with Mn. Withdrawal of Mn, with or without inhibiting the cholestero l biosynthesis, also corrected the Mn-induced learning defect. These r esults suggest that Mn toxicity produces learning disability by increa sing cholesterol biosynthesis and this reversible disability in learni ng can be corrected by withdrawal of Mn exposure.