Document Type

Honors Thesis

Publication Date

Spring 5-2016

Abstract

The present study attempts to investigate a potential underlying mechanism that contributes to cognitive impairments associated with chemotherapy treatment. In addition, it looks to investigate the potential preventative treatment using an antidepressant agent (Fluoxetine) to reduce the effects observed by chemotherapy treatment. One proposed explanation for Chemo Brain is a reduction in the proliferation of new brain cells. This study was designed to investigate this mechanism and was conducted in a series of two experiments. In experiment 1, 37 C57BL/6J male mice were administered saline or one of two chemotherapy agents; Cyclophosphamide or Doxorubicin over the course of eight days. Neural tissue was examined at 56 days and 6 months post chemotherapy administration to evaluate the effects of chemotherapy on cellular proliferation. A two-way ANOVA was performed on the 56 day and 6 month data. Analysis revealed no significant effect of treatment at either time point. A significant effect of day was observed.

In experiment two, 41 C57BL/6J male mice underwent treatment of saline, the chemotherapy agent 5-FU and saline, or an administration of Fluoxetine followed by an administration of 5-FU. Similarly, cellular proliferation in the neural tissue was measured at 56 days and 6 months post chemotherapy administration. A two-way ANOVA revealed no significant effect of treatment at either time point but a significant effect of time was observed. Overall, our results indicate that further research is needed to fully understand the long-term impacts of chemotherapy on neurogenesis and the potential use of neuroprotectant Fluoxetine as a preventative treatment. While the results of this study do not directly support the hypothesis that chemotherapy agents are capable of altering neurogenesis, more work will be required to identify the conditions under which such effects do or do not occur.

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