Abstract 2611: Cisplatin negatively affects CNS progenitor cells and behavior in the adult mouse

Abstract

Abstract Patients that are treated with chemotherapy exhibit long term changes in cognitive function, decreasing quality of life (Van Dam et al 1998). Although much work has been done characterizing these changes in the patient, there is little research on the possible cellular changes. Additionally, little has been done studying the effects of a single chemotherapeutic agent on cognitive function. Our laboratory has previously shown that chemotherapy, including cisplatin, decreases neural progenitor cell division and increases cell death in the mouse brain (Dietrich et al 2006; Han et al., 2008). Here, we have studied the effects of cisplatin on CNS progenitor cells and also on behavior. We found that cisplatin negatively affects progenitor cells throughout the CNS: progenitor cells migrating from the subventricular zone to the olfactory bulb, the olfactory epithelium, the dentate gyrus of the hippocampus and the corpus callosum. The subventricular zone, rostral migratory stream and olfactory bulb all showed increases in cell death and decreases in the neuroblast population. This change in progenitor cell numbers remained significant compared to vehicle control for as long as six months. In the olfactory epithelium, we found a significant decrease in proliferation of olfactory receptor neuron (ORN) progenitor cells. There was also a decrease in proliferation and an increase in cell death in the oligodendrocyte precursor cell (OPC) population of the corpus callosum and in the dentate gyrus. Using a fixed interval-60s operant schedule we examined the effects of cisplatin on performance. This schedule allows for the operant response rate to vary widely without altering the rate of reinforcement. When compared to the vehicle control, we found significant changes in response rate. These findings demonstrate that even in the absence of underlying cancer, cisplatin has adverse effects on CNS progenitor cells in multiple regions and negatively impacts behavioral outcomes. This work provides animal models of potential value in developing treatments to prevent the neurotoxic side effects of cisplatin, thus improving quality of life in recipients of this therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2611.