Chemotherapy, Neurotoxicity, and Cognitive Decline: Developing a Mouse Model and Potential Interventions.

摘要

Adjuvant chemotherapy often causes cognitive decline in breast cancer survivors. Although the cognitive deficits are often temporary, it appears that for at least a subset of survivors, the deficits last for years and can have a deleterious impact on survivor quality of life. Recent evidence shows that chemotherapy agents can have longlasting neurotoxic effects: increase in cell death and decrease in cell division/proliferation in the SVG, the DG, and the CC, as well as delayed myelin degeneration. Which chemotherapy agents or combinations of agents cause CNS damage remains unclear. Our study was designed to determine 1) if doxorubicin or cyclophosphamide cause a decrease in neurogenesis and/or myelin damage and 2) if neurogenesis and/or myelin damage caused by 5-Fluorouracil can be prevented by pre and co-treatment with antidepressants or antioxidants. The results from our auditory brainstem response experiments suggest that 5-Fluorouracil and cyclophosphamide cause a transient speed of processing deficit, while doxorubicin does not. In addition, our results suggest that co-treatment with antioxidants does not prevent the transient speed of processing deficit. Our immunocytochemistry experiments are ongoing and will help us determine if doxorubicin or cyclophosphamide cause a long lasting decline in neurogensis, as does 5- Flourouracil, and if antidepressants or antioxidants can prevent such damage.