Transcriptomic changes upon doxorubicin treatment in the brain of ApoE3 and ApoE4 rats

Many pediatric cancer survivors experience chemotherapy-induced cognitive impairment (CICI), which negatively impacts the quality of life and the interpatient variability in susceptibility to CICI is not well understood. Among pediatric cancer survivors, those with the E4 allele of Apolipoprotein E (ApoE) are more likely to exhibit cognitive dysfunction than those with the more prevalent ApoE3 allele, suggesting the ApoE4 allele increases susceptibility to CICI. To mimic a curative pediatric treatment regimen, in our experimental model, five-week-old rats homozygous for either human ApoE3 or ApoE4 allele were treated with doxorubicin (2mg/kg/week for 4 weeks) or PBS (saline). This study aims to investigate transcriptomic changes in different regions of brain to determine the impact of doxorubicin treatment in ApoE3 and ApoE4 rats. Overall design: RNA-Sequencing was performed to characterize changes in different regions of the brain (cortex and hippocampus) of ApoE3 and ApoE4 rats after doxorubicin treatment. Rats were treated with doxorubicin (2 mg/kg/week for 4 weeks) starting at the age of 5 weeeks. 5-6 weeks after the last doxorubicin treatment, the hippocampus and cortex regions of the brains were collected for RNA-seq.