Treadmill and wheel exercise alleviate lipopolysaccharide-induced short-term memory impairment by enhancing neuronal maturation in rats

Lipopolysaccharide (LPS) is an endotoxin derived from Gram-negative bacteria, which induces brain inflammation. LPS-induced brain inflammation deteriorates hippocampus-dependent cognitive deficits. In the present study, we investigated the effects of forced treadmill exercise and voluntary wheel exercise on short-term memory in relation to neuronal maturation in LPS-induced brain inflammation of rats. Brain inflammation in rats was induced by an injection of LPS into the cerebral ventricle. Short-term memory was evaluated using a step-down avoidance task. Cell proliferation in the hippocampal dentate gyrus was determined by 5-bromo-2'-deoxyuridine (BrdU), a marker of new cells, immunohistochemistry. Western blot analysis for the determination of doublecortin (DCX), a marker of immature neurons and neuronal nuclear antigen (NeuN), a marker of mature neurons, was performed. In the present study, LPS-induced brain inflammation impaired short-term memory by increasing DCX expression and suppressing NeuN expression. These results suggest that LPS-induced brain inflammation disturbs neuronal maturation. The number of BrdU-positive cells in the hippocampal dentate gyrus was increased by LPS injection. This increase in the number of BrdU-positive cells can be ascribed to the increase in the number of of immature neurons following LPS injection. On the other hand, forced treadmill exercise and voluntary wheel exercise improved brain inflammation-induced short-term memory impairment by suppressing DCX expression and increasing NeuN expression, enhancing neuronal maturation. Forced treadmill exercise and voluntary wheel exercise showed similar efficacy. From these results, it can be inferred that forced treadmill exercise and voluntary wheel exercise may improve memory function deteriorated by brain inflammation.