Effects of acute treadmill running following administration of lipopolysaccharide on subsequent changes in microglial activation and depressive-like behavior in rats.

The mechanisms underlying the beneficial effects of physical exercise on the brain, including its antidepressant properties, have yet to be fully elucidated. Recently, there has been growing interest that the beneficial effects of physical exercise may be related to its ability to reduce neuroinflammation by modulating microglial activation in the brain. However, no studies have investigated the relationship between microglial activation and depressive symptoms in the context of exercise intervention. The goal of the study was to assess if exercise would reduce depression-like behaviors and microglia activation induced by lipopolysaccharide (LPS). Here, we examined whether a bout of treadmill running (15 m/min, 30 min) performed 2 h after the administration of LPS (0.83 mg/mL/kg, i.p.) would affect subsequent changes in microglial activation and depressive-like behavior in rats. Microglial activation was assessed by alterations in microglial morphology (somatic cell size) in the dorsal raphe nucleus (DRN), hippocampal dentate gyrus (DG) and hypothalamic paraventricular nucleus (PVN), which were selected based on their involvement in stress regulation and the pathophysiology of depression, performing immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1). In addition, we performed a forced swim test (FST) in the LPS-treated rats to assess the antidepressant effect of physical exercise on inflammation-induced depression. The increase of the somatic area of Iba1-positive cells in the DRN and DG at 24 h after LPS administration was significantly attenuated by a bout of acute and mild treadmill running performed 2 h after LPS administration. In addition, the LPS-induced increase of immobility time in the FST was significantly suppressed by the acute treadmill running. These results suggest that mild physical exercise can suppress microglia-induced neuroinflammation and exert an antidepressant effect against inflammation-induced depression.