IGF-1 Partially Restores Chemotherapy-Induced Reductions in Neural Cell Proliferation in Adult C57BL/6 Mice

ABSTRACT

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.

Keywords: :

• Chemotherapy
• Cancer treatment
• Cognitive impairment
• Neural cell proliferation
• Neurogenesis
• IGF-1

ACKNOWLEDGMENTS

These studies were supported by DOD BC021198 (RAG) and NCI R25CA01618 (MCJ, GRM).