The Distant Molecular Effects on the Brain by Cancer Treatment.

Cancer survivors experience cancer-related cognitive impairment (CRCI) secondary to treatment. Chemotherapy and radiation therapy independently contribute to cognitive dysfunction; however, the underlying mechanisms leading to dysfunction remain unclear. We characterized brain gene expression changes in a mouse model of CRCI to identify the mechanistic underpinnings. Eleven-to-twelve-week-old SKH1 mice were treated with doxorubicin (DOX), hindlimb radiation (RT), concurrent hindlimb radiation and doxorubicin (DOX-RT), or no treatment (control). Sixteen days following treatment, gene expression was measured from murine brains using the NanoString nCounter glial profiling panel. Gene expression was normalized and compared between groups. No two groups shared the same expression pattern, and only and were upregulated in multiple treatment groups. Brains from DOX-treated mice had upregulated , , , , and and downregulated expression compared to control brains. Brains from RT-treated mice demonstrated increased and and decreased and expression compared to control brains. Brains from DOX-RT-treated mice had upregulated , , , , , and expression and downregulated and expression compared to control brains. The gene expression changes demonstrated here highlight roles for neuronal transmission and oxidative stress in the pathogenesis of doxorubicin-related CRCI and inflammation in RT-related CRCI.