Rat prefrontal cortex whole genome bisulfite sequencing after chemotherapy treatment

Systemic chemotherapy treatment is associated with long-term cognitive impairment inbreast cancer survivors. This phenomenon is termed as chemotherapy-induced cognitive impairment (CICI). Many studies have established the extent of altered cognition and its corresponding regions in the brain most affected. Several potential molecular mechanisms have been proposed that explain these changes. Our lab and others have proposed oxidative stress and neuroinflammation in CICI. These mechanisms have strong ties to epigenetic factors. In this study Presented here, we have focused on identifying epigenetic factors that may cause chemotherapy induced cognitive impairment. We have found that doxorubicin and cyclophosphamide treatment cause the emergence of new DNA methylation pattern in specific genes that are essential for neuronal development in prefrontal cortex of female rat brain. This study also found that there is an increase in histone deacetylase activity in the PFC of female rat brain. In summary, our findings create a road map to recognize epigenetic factors involved chemotherapy-induced cognitive impairment. Identifying these factors can potentially develop intervention for CICI in cancer survivors.