Chemotherapy treatment linked to lasting cognitive changes in rats

Researchers at The City College of New York have linked chemotherapy treatment to lasting cognitive changes in rats – potentially shading light, for the first time, on cognitive problems some cancer survivors experience long after treatment ends. Entitled "Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain," the study appears in the journal Nature: Scientific Reports.

Our study explored how chemotherapy affects the brain at the molecular level using an animal model. We found that chemotherapy doesn't just target cancer cells - it also disrupts how genes are regulated in the brain, specifically in the prefrontal cortex, the area responsible for decision-making and executive function."

Karen Hubbard, study's co-lead, professor of biology in CCNY's Division of Science

For the first time, the team showed that a commonly used chemotherapy combination - doxorubicin and cyclophosphamide - significantly increases the expression of DNMT3a, a gene involved in adding methylation marks to DNA. This change was linked to altered DNA methylation patterns in key brain regions, which may help explain why many cancer patients experience long-term cognitive issues after treatment, often referred to as "chemo brain."

The study, Hubbard added, offers a biological explanation for these cognitive problems that many cancer survivors, especially breast cancer patients, report long after treatment ends.

This may help to identify patients who are most vulnerable to cognitive side effects, and guide the development of targeted epigenetic therapies, such as DNMT or HDAC inhibitors, to prevent or even reverse chemotherapy-induced cognitive decline.

The research continues at CCNY with focus on investigating the role of RNA-binding proteins, which are known to be involved in brain aging, in both the prefrontal cortex and hippocampus of the team's chemotherapy-treated animal model. "This work aims to further uncover how chemotherapy disrupts molecular pathways linked to cognitive decline."

Other members of Hubbard's team include (all CCNY unless indicated): Shami Chakrabarti, Chanchal Wagh, Ciara Bagnall-Moreau (CCNY/Institute of Molecular Medicine, The Feinstein Institute of Medical Research), Fathema Uddin, Joshua Reiser, Kaliris Salas-Ramirez (CUNY School of Medicine), and Tim Ahles (Memorial Sloan Kettering Cancer Center).