Cognitive impairments caused by oxaliplatin and 5-fluorouracil chemotherapy are ameliorated by physical activity
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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.
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.
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.
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.
KeywordsChemotherapy Cognition Oxaliplatin 5-Fluorouracil Exercise
- Bourke RS, West CR, Chheda G, Tower DB (1973) Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Canc Res 33:1735–1746Google Scholar
- Formica V, Leary A, Cunningham D, Chua YJ (2006) 5-Fluorouracil can cross brain–blood barrier and cause encephalopathy: should we expect the same from capecitabine? a case report on capecitabine-induced central neurotoxicity progressing to coma. Canc Chemother Pharmacol 58:276–278CrossRefGoogle Scholar
- Mar Fan HG, Clemons M, Xu W, Chemerynsky I, Breunis H, Braganza S, Tannock IF (2008) A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer. Support Care Canc 16:577–583CrossRefGoogle Scholar
- Vardy JL, Rourke S, Pond GR, Galica J, Park A, Dhillon H, Clarke SJ, Tannock IF (2010) Cognitive function and fatigue in cancer patients after chemotherapy: a longitudinal cohort study in patients with colorectal cancer (CRC). ICCTF, Cognition & Cancer Conference. ICCTF, New YorkGoogle Scholar