title: Environmental enrichment protects against cognitive impairment following chemotherapy in an animal model.
abstract: Clinical studies indicate that up to 70% of cancer patients who receive chemotherapy experience cognitive impairment. The present study investigated environmental enrichment as a protective factor against the adverse effects of anticancer drugs on cognitive and biological processes in an animal model. Adult rats were housed in group cages with environmental stimulation or in standard cages for 3 months, before receiving 3 weekly injections of methotrexate + 5-fluorouracil, or equal volumes of saline. Rats were then administered tests of learning and memory that are sensitive to hippocampal or frontal lobe dysfunction. The relationship between cognitive performance and hippocampal neurogenesis was examined through sensitive time-dependent measures of neuronal maturation. Chemotherapy-treated rats in the standard environment were impaired on tests of spatial memory, nonmatching-to-sample (NMTS) rule learning, and delayed-NMTS. Chemotherapy-treated rats in the enriched environment performed at or near normal levels. The performance of the chemotherapy groups on the hippocampus-sensitive, spatial memory and delayed-NMTS tests correlated with neurogenesis levels. The results show that environmental enrichment can reduce the risk of chemotherapy-induced cognitive impairment, in part by promoting neuronal differentiation and growth during cell maturation. As well, they point to the importance of lifestyle factors in treating or preventing adverse effects of anticancer drugs on cognitive function. (PsycINFO Database Record
authors.affiliation: Rotman Research Institute.
authors.forename: Gordon
authors.initials: G
authors.lastname: Winocur
authors.affiliation: Department of Physiology, University of Toronto.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Wojtowicz
authors.affiliation: Department of Physiology, University of Toronto.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Merkley
authors.affiliation: Division of Medical Oncology.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000517:prevention & control; D004195:Disease Models, Animal; D004358:Drug Therapy / Q000379:methods*; D004777:Environment; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D006624:Hippocampus; D008727:Methotrexate / Q000009:adverse effects; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil; D008727:Methotrexate