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The effect of manganese-induced hypercholesterolemia on learning in rats
1Akdeniz University, Faculty of Medicine, Department of Physiology, Antalya, Turkey.
Abstract:
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.
Insights
Manganese (Mn) exposure slows learning in rats by increasing hippocampal cholesterol. Inhibiting cholesterol biosynthesis corrected this learning deficit, suggesting hypercholesterolemia mediates Mn-induced learning disability.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- The precise mechanism behind manganese (Mn)-induced learning disabilities remains unclear.
- Elevated cholesterol levels have been implicated in various neurological disorders.
Purpose of the Study:
- To investigate the role of elevated cholesterol in manganese-induced learning disability.
- To determine if inhibiting cholesterol biosynthesis can ameliorate Mn-induced cognitive deficits.
Main Methods:
- Rats were exposed to two different doses of manganese (357 and 714 micrograms/kg) daily for 39 days.
- Learning was assessed using a T-maze task measuring the time to reach a food reward.
- Cholesterol levels in the hippocampus were measured, and the effect of a cholesterol biosynthesis inhibitor was evaluated.
Main Results:
- Manganese exposure led to significant accumulation of Mn and increased cholesterol in the hippocampus.
- Mn-exposed rats exhibited significantly slower learning times in the T-maze task.
- Co-administration of a cholesterol biosynthesis inhibitor normalized learning times and hippocampal cholesterol levels without affecting Mn levels.
Conclusions:
- Manganese-induced hypercholesterolemia plays a critical role in the development of learning disabilities.
- Targeting cholesterol biosynthesis may offer a therapeutic strategy for mitigating Mn-induced cognitive impairments.