Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation

Feb 26, 2024Redox biology

Aerobic exercise may reduce brain inflammation and improve thinking problems caused by LPS

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Abstract

Aerobic exercise improved memory and cognitive deficits in amnesic mice exposed to lipopolysaccharide.

Aerobic exercise training was conducted 5 days per week for 4 weeks on a motorized treadmill.
Significant increases in protein levels of FNDC5 were observed, which activates neuroprotective markers BDNF and CREB.
Aerobic exercise led to reduced microglial-mediated neuroinflammation and lower expression of BACE-1 in the hippocampus and cerebral cortex.
Irisin treatment in BV-2 microglial cells blocked specific inflammatory signaling pathways and reduced levels of inflammation markers.
The findings suggest that aerobic exercise may enhance spatial learning and cognitive functions by inhibiting neuroinflammation.

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Physical activity has been considered an important non-medication intervention in preserving mnemonic processes during aging. However, how aerobic exercise promotes such benefits for human health remains unclear. In this study, we aimed to explore the neuroprotective and anti-inflammatory effects of aerobic exercise against lipopolysaccharide (LPS)-induced amnesic C57BL/6J mice and BV-2 microglial cell models. In the in vivo experiment, the aerobic exercise training groups were allowed to run on a motorized treadmill 5 days/week for 4 weeks at a speed of 10 rpm/min, with LPS (0.1 mg/kg) intraperitoneally injected once a week for 4 weeks. We found that aerobic exercise ameliorated memory impairment and cognitive deficits among the amnesic mice. Correspondingly, aerobic exercise significantly increased the protein expressions of FNDC5, which activates target neuroprotective markers BDNF and CREB, and antioxidant markers Nrf2/HO-1, leading to inhibiting microglial-mediated neuroinflammation and reduced the expression of BACE-1 in the hippocampus and cerebral cortex of amnesic mice. We estimated that aerobic exercise inhibited neuroinflammation in part through the action of FNDC5/irisin on microglial cells. Therefore, we explored the anti-inflammatory effects of irisin on LPS-stimulated BV-2 microglial cells. In the in vitro experiment, irisin treatment blocked NF-κB/MAPK/IRF3 signaling activation concomitantly with the significantly lowered levels of the LPS-induced iNOS and COX-2 elevations and promotes the Nrf2/HO-1 expression in the LPS-stimulated BV-2 microglial cells. Together, our findings suggest that aerobic exercise can improve the spatial learning ability and cognitive functions of LPS-treated mice by inhibiting microglia-mediated neuroinflammation through its effect on the expression of BDNF/FNDC5/irisin.

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Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation

Abstract

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