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.
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.
Authors: Michiel B de Ruiter; Liesbeth Reneman; Willem Boogerd; Dick J Veltman; Frits S A M van Dam; Aart J Nederveen; Epie Boven; Sanne B Schagen Journal: Hum Brain Mapp Date: 2010-07-28 Impact factor: 5.038
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