Cognitive impairments caused by oxaliplatin and 5-fluorouracil chemotherapy are ameliorated by physical activity

Abstract

Rationale Studies in women with breast cancer, and in animal models, have demonstrated that chemotherapy can have a negative impact on cognitive function. Which chemotherapy agents cause problems with cognition and the aetiology of the impairment is unknown. Furthermore, there is no proven treatment. Objectives This study aimed to evaluate the effects of 5-fluorouracil (5FU) and oxaliplatin (OX) chemotherapy agents commonly used to treat colorectal cancer on cognition in laboratory rodents. Furthermore, we assessed physical activity as a potential remedy for the observed chemotherapy-induced cognitive deficits. Results In rodents, treatment with 5FU and OX alone impairs memory as measured by novel object recognition. But combined treatment appears to have greater detrimental effects on hippocampal-dependent tasks, contextual fear recall and spatial reference memory (water maze), yet had no effect on cued fear recall, a non-hippocampal task. These impairments were prevented by 4 weeks of wheel running overnight after 5FU/OX treatment. We found a significant interaction between chemotherapy and exercise: rats receiving both 5FU/OX and exercise had improved cognition relative to non-exercising 5FU/OX rats on novel object recognition and spatial reference memory. Conclusions The combination 5FU/OX had a significant impact on cognition. However, rats treated with 5FU/OX that exercised post chemotherapy had improved cognition relative to non-exercising rats. This suggests that physical activity may prove useful in ameliorating the cognitive impairments induced by 5FU/OX. © 2011 Springer-Verlag.