Treadmill exercise ameliorates chemotherapy-induced memory impairment through Wnt/β-catenin signaling pathway

• Published in: Journal of exercise rehabilitation Vol. 19; no. 6; pp. 314 - 319
• Main Authors: Park, Sang-Seo, Kim, Sang-Hoon, Kim, Bo-Kyun, Shin, Mal-Soon, Jeong, Hyun-Tae, Park, Jong-Suk, Kim, Tae-Woon
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Exercise Rehabilitation 01.12.2023; 한국운동재활학회
• Subjects: Original; 심리과학; Treadmill exercise; Wnt/β-catenin signaling; Mitochondrial Ca2+ re-tention capacity; Doxorubicin; Proin-flammatory cytokine; Short-term memory; Mitochondrial Ca2+ retention capacity; Proinflammatory cytokine
• ISSN: 2288-176X; 2288-1778
• DOI: 10.12965/jer.2346594.297

Doxorubicin (DOX) is a widely used chemotherapy drug for various cancers and it is known to induce cognitive impairment. The aim of this study was to investigate the effect of treadmill exercise on chemother-apy-induced memory impairment. We assessed whether DOX affects inflammation, mitochondrial Ca2+ retention capacity, and Wnt/β-catenin signaling. Male Sprague-Dawley rats were divided into control group, exercise group, DOX-injection group, and DOX-injection and exercise group. To create a DOX-induced memory impairment model, animals were injected intraperitoneally with DOX (2 mg/kg) dissolved in saline solution once a week for 4 weeks. Treadmill exercise was performed once a day, 5 days a week, for 8 consecutive weeks. Short-term memo-ry was determined using the step-down avoidance test. Western blot was performed for the proinflammatory cytokines, Wnt/β-catenin sig-naling, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) in the hippocampus. Mitochondrial Ca2+ retention ca-pacity in the hippocampus was also measured. DOX-injection rats showed deterioration of short-term memory along with decreased ex-pression of BDNF and TrkB in the hippocampus. Levels of the proinflam-matory cytokines, tumor necrosis factor-α and interleukin-6, were in-creased in the DOX-injection rats. Wnt/β-catenin signaling was activat-ed and mitochondrial Ca2+ retention capacity was decreased in the DOX-injection rats. However, treadmill exercise alleviated short-term memory impairment, decreased proinflammatory cytokines, increased BDNF and TrkB expression, and enhanced mitochondrial Ca2+ retention capacity. Treadmill exercise restorated Wnt/β-catenin signaling path-way. This study demonstrated that treadmill exercise can be used for patients undergoing chemotherapy with DOX.