THE EFFECT OF MANGANESE-INDUCED HYPERCHOLESTEROLEMIA ON LEARNING IN RATS

Since the exact mechanism of manganese (Mn)-induced learning disabilit y is not known, we investigated the role of elevated cholesterol in ra ts exposed daily to 357 and 714 mu g Mn/kg for 30 d. Significant Mn ac cumulation was accompanied by increased cholesterol content in the hip pocampal region of Mn-treated rats. The learning, which is based on th e time needed to reach food placed at the exit of a T-maze after a 1-d training period, was significantly slower in exposed rats than in une xposed rats. The rats receiving 357 and 714 mu g Mn/kg reached the foo d in 104.5 +/- 13.8 and 113.3 +/- 25.7 s, respectively, on d 30, where as their untreated counterparts reached the food in 28.7 +/- 11.4 s. T his delay was completely corrected to 29.3 +/- 7.8 and 30.7 +/- 6.0 s in rats with coadministration of an inhibitor of cholesterol biosynthe sis with 357 and 714 mu g/kg of Mn. The correction of impaired learnin g was associated with the normalization of hippocampal cholesterol, bu t the Mn level in this region of the brain was not influenced in rats treated with a drug that inhibits cholesterol biosynthesis. These resu lts suggested that Mn-induced hypercholesterolemia is involved in Mn-d ependent learning disability.