Reversibility of manganese-induced learning defect in rats

In this study the mechanism by which manganese (Mn) induces learning defect and its reversibility has been investigated in rats. Female albino rats were dosed orally with 357 micrograms 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) administration 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 days without Mn). Mevinolin was given orally at 235.7 micrograms/kg body weight. Significant increases in the Mn and cholesterol levels in the hippocampus were accompanied by an obvious slowness in learning of rats exposed to Mn. After one training period (day 29) the time required to reach the exit of a T-maze was 104.5 +/- 13.8 sec for rats dosed with Mn for 30 days, whereas that of the controls was 28.7 +/- 11.4 sec on day 30. This delay was completely corrected (to 30.7 +/- 6.0 sec) in rats co-administered mevinolin (an inhibitor of cholesterol biosynthesis) with Mn. Withdrawal of Mn, with or without inhibiting the cholesterol biosynthesis, also corrected the Mn-induced learning defect. These results suggest that Mn toxicity produces learning disability by increasing cholesterol biosynthesis and this reversible disability in learning can be corrected by withdrawal of Mn exposure.