Exercise mitigates cisplatin-induced neurotoxicity in murine hippocampus via attenuation of neuroinflammation and synaptic plasticity

Chemotherapy-induced cognitive impairment is recognized as the most typical symptom in patients with cancer that occurs during and following the chemotherapy treatment. Recently many studies focused on pharmaceutical strategies to control the chemotherapy side effects, however it is far from satisfactory. There may be a need for more effective treatment options. The aim of this study was to investigate the protective effect of exercise on cisplatin-induced neurotoxicity. Eight-week-old C57BL6 mice were separated into three group: normal control (CON, n=8); cisplatin injection control (Cis-CON, n=8); cisplatin with aerobic exercise (Cis-EXE, n=8). Cisplatin was administered intraperitoneally at a dose of 3.5 mg/kg/day. The Cis-EXE group exercise by treadmill running (14~16m/min for 45 min daily, 3 times/week) for 12 weeks. Compared to the CON group, the cisplatin injection groups showed significant decrease in body weight and food intake, indicating successful induction of cisplatin toxicity. The Cis-CON group showed significantly increased levels of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-a in the hippocampus, while the Cis-EXE group was significantly decreased in the expression of IL-6, IL-1β, and TNF-a. In addition, compared to the CON group, the levels of synapse-related proteins including synapsin-1 and -2 were significantly reduced in the Cis-CON group, and there was a significant difference between the Cis-CON and Cis-EXE groups. Antioxidant and apoptosis factors were significantly improved in the Cis-EXE group compared with the Cis-CON group. This study suggest that exercise could be meaningful approach to prevent or improve cisplatin-induced cognitive impairment.