Treatment with cyclophosphamide in post-weaning mice causes prolonged suppression of neural stem cell proliferation in the hippocampal dentate gyrus

Abstract

The effects of anticancer drugs used in childhood on brain function in adulthood are unclear. Here, we report the long-term changes in the proliferation of neuronal stem/progenitor cells (NPCs) in the hippocampal dentate gyrus after treatment with cyclophosphamide (CYP), which is often used as a therapeutic medicine in childhood cancer. A systemic injection of CYP into 3-week-old mice decreased 5-bromo-2'-deoxyuridine (BrdU)-incorporated cells in the hippocampal subgranular zone 2 and 55 days after the injection in a dose-dependent manner. Restraint stress induced increase in corticosterone level, which was enhanced by CYP at day 35 after injection. These findings suggest that CYP injection into post-weaning mice causes prolonged alteration in NPC proliferation in the hippocampus and the stress response.

Keywords: Behavior; Cyclophosphamide; Late effect; Neurogenesis; Stress response.