The effect of manganese-induced hypercholesterolemia on learning in rats.
Since the exact mechanism of manganese (Mn)-induced learning disability is not known, we investigated the role of elevated cholesterol in rats exposed daily to 357 and 714 micrograms Mn/kg for 39 d. Significant Mn accumulation was accompanied by increased cholesterol content in the hippocampal region of Mn-treated rats. The learning, which is based on the 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 unexposed rats. The rats receiving 357 and 714 micrograms Mn/kg reached the food in 104.5 +/- 13.8 and 113.3 +/- 25.7 s, respectively, on d 30, whereas their untreated counterparts reached the food in 28.7 +/- 11.4 s. This delay was completely corrected to 29.3 +/- 7.8 and 30.7 +/- 6.0 s in rats with coadministration of an inhibitor of cholesterol biosynthesis with 357 and 714 micrograms/kg of Mn. The correction of impaired learning was associated with the normalization of hippocampal cholesterol, but the Mn level in this region of the brain was not influenced in rats treated with a drug that inhibits cholesterol biosynthesis. These results suggested that Mn-induced hypercholesterolemia is involved in Mn-dependent learning disability.
Sentürk
U K
UK
Akdeniz University, Faculty of Medicine, Department of Physiology, Antalya, Turkey.
Oner
G
G
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008345:Manganese / Q000008:administration & dosage / Q000493:pharmacokinetics; D020149:Manganese Poisoning; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats
D000924:Anticholesteremic Agents; D008345:Manganese; D002784:Cholesterol; D008148:Lovastatin