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Cognitive impairment and decreased hippocampal neurogenesis after treatment with chemotherapeutic drugs
Author(s) -
Pechnick Robert N,
Reyes Kevin C,
Das Melanie,
Lacayo Liliana M,
Farrokhi Catherine,
Zonis Svetlana,
Chesnokova Vera
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.582.2
Subject(s) - neurogenesis , hippocampal formation , dentate gyrus , cyclophosphamide , medicine , spontaneous alternation , chemotherapy , methotrexate , hippocampus , pharmacology , bromodeoxyuridine , oncology , endocrinology , psychology , neuroscience , immunohistochemistry
Post‐chemotherapy cognitive impairment has long been recognized in cancer survivors; however, at the present time the cause(s) is not known. The objective of the present study was to determine the effects of chemotherapeutic drugs on cognitive function and hippocampal neurogenesis in the mouse. Adult female mice were injected once a week for 3 weeks with methotrexate (30 mg/kg/i.p.), cyclophosphamide (100 mg/kg/i.p.) or saline (0.9%/i.p.). One week after the last injection they underwent behavioral testing. Another cohort of mice did not undergo behavioral testing, but were treated with bromodeoxyuridine (BrdU; 50 mg/kg/i.p.; every 2 hr for a total of 4 injections) and sacrificed 24 hr later. There were no significant differences in locomotor activity among the treatment groups; however, spontaneous alternation was impaired in the methotrexate‐treated subjects. BrdU incorporation was not affected in the cyclophosphamide‐treated subjects, but was markedly reduced in the dentate gyrus of the hippocampus after treatment with methotrexate. These results suggest that post‐chemotherapy cognitive impairment might be linked to drug‐induced decreases in hippocampal neurogenesis. Supported by Department of Defense Breast Cancer Research Program grant number BC075629.