IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice.
Chemotherapeutic agents produce persistent difficulties in memory through an unknown mechanism. We tested the hypothesis that chemotherapeutic agents readily able to cross the blood-brain barrier (cyclophosphamide and fluorouracil), as opposed to those not known to readily cross the barrier (paclitaxel and doxorubicin), reduce neural cell proliferation following chemotherapy. We found that 5-bromo-2-deoxyuridine labeling following chemotherapy given to C57BL/6 mice revealed a similar reduction in neural cell proliferation in the dentate gyrus for all four agents. Insulin-like growth factor 1, a molecule implicated in promoting neurogenesis, counteracted the effects of high doses of chemotherapy on neural cell proliferation.
Janelsins
Michelle C
MC
Department of Radiation Oncology, University of Rochester Medical Center, New York 14642, USA. michelle_janelsins@urmc.rochester.edu
Roscoe
Joseph A
JA
Berg
Michel J
MJ
Thompson
Bryan D
BD
Gallagher
Mark J
MJ
Morrow
Gary R
GR
Heckler
Charles E
CE
Jean-Pierre
Pascal
P
Opanashuk
Lisa A
LA
Gross
Robert A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D001812:Blood-Brain Barrier; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity; D018891:Dentate Gyrus / Q000187:drug effects*; D004317:Doxorubicin / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D017239:Paclitaxel / Q000633:toxicity; D015431:Weight Loss
D000970:Antineoplastic Agents; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin; D003520:Cyclophosphamide; D001973:Bromodeoxyuridine; D017239:Paclitaxel; D005472:Fluorouracil