IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice

Cancer Invest. 2010 Jun;28(5):544-53. doi: 10.3109/07357900903405942.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / toxicity*
  • Blood-Brain Barrier*
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation / drug effects
  • Cyclophosphamide / toxicity
  • Dentate Gyrus / drug effects*
  • Doxorubicin / toxicity
  • Fluorouracil / toxicity
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis / drug effects
  • Neurons / drug effects
  • Paclitaxel / toxicity
  • Weight Loss

Substances

  • Antineoplastic Agents
  • Insulin-Like Growth Factor I
  • Doxorubicin
  • Cyclophosphamide
  • Bromodeoxyuridine
  • Paclitaxel
  • Fluorouracil