title: Physical exercise prevents suppression of hippocampal neurogenesis and reduces cognitive impairment in chemotherapy-treated rats.
abstract: BACKGROUND
  Chemotherapy, used for the treatment of cancer, often produces cognitive impairment that has been related to suppression of neurogenesis. Physical exercise, which promotes neurogenesis, is known to improve cognitive function in neurologically challenged animals and humans. It is unknown whether exercise similarly protects against chemotherapy-induced cognitive impairment and whether recovery of neurogenesis is a critical factor.
  
  
  OBJECTIVE
  The present study investigated the relationship between hippocampal neurogenesis and cognitive performance in chemotherapy-treated rats that engaged in different amounts of physical activity.
  
  
  METHODS
  Groups of rats, housed individually in standard cages or in specially designed cages that allowed unlimited access to a running wheel, received three injections of the chemotherapeutic drugs methotrexate and 5-fluorouracil, or equal volumes of saline. They were then administered the following cognitive tests in a water maze: (1) spatial memory (SM), (2) cued memory, (3) non-matching to sample (NMTS) rule learning; (4) delayed NMTS (DNMTS). Hippocampal neurogenesis was quantified by counting doublecortin-expressing cells in the dentate gyrus.
  
  
  RESULTS
  Chemotherapy administered to rats in standard cages resulted in a significant reduction in hippocampal neurogenesis and impaired performance on the SM, NMTS, and DNMTS tasks. In rats receiving chemotherapy and housed in exercise cages, neurogenesis was not suppressed and cognitive performance was similar to controls.
  
  
  CONCLUSIONS
  Physical exercise can reduce cognitive deficits that result from chemotherapy and this effect is mediated, at least in part, by preventing suppression of drug-induced hippocampal neurogenesis. The results suggest benefits of exercise in preventing or treating cognitive impairment associated with chemotherapy.
authors.affiliation: Baycrest Centre, Rotman Research Institute, 3560 Bathurst St, Toronto, Ontario, Canada, M6A 2E1, gwinocur@research.baycrest.org.
authors.forename: Gordon
authors.initials: G
authors.lastname: Winocur
authors.forename: J Martin
authors.initials: JM
authors.lastname: Wojtowicz
authors.forename: Johnny
authors.initials: J
authors.lastname: Huang
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001835:Body Weight; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D003463:Cues; D018891:Dentate Gyrus / Q000187:drug effects* / Q000503:physiopathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D006799:Housing, Animal; D007150:Immunohistochemistry; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008727:Methotrexate / Q000009:adverse effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009483:Neuropsychological Tests; D020318:Rats, Long-Evans; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D000964:Antimetabolites, Antineoplastic; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D005472:Fluorouracil; D008727:Methotrexate