Abstract:

The process of generating new neurons in the hippocampus, or hippocampal neurogenesis, is putatively regarded as a principle target of chemotherapy- and radiotherapy-induced side effects, particularly in relation to cognitive deficits. Following chemotherapy or radiotherapy, experimental animals exhibit significant reductions in neurogenesis and cell proliferation in the dentate gyrus of the hippocampus in conjunction with memory impairments across diverse behavioral paradigms. Reductions in neurogenesis and diminished memory capabilities have also been observed following relatively low doses of ionizing radiation (e.g., 2 Gy of γ-ray and 0.8 Gy of neutrons) or cyclophosphamide treatment (40 mg/kg, intraperitoneal [i.p.]), but these changes are reversible over time. However, exposure to relatively high doses of γ-ray (10 Gy) irradiation or methotrexate (MTX; 40 mg/kg, i.p.) treatment results in long-lasting alterations of neurogenesis and memory function.