Chemo Brain Explained: Rat Study Reveals Molecular Clues

New research pinpoints gene activity changes in brain regions crucial for cognition

Scientists have uncovered a potential molecular basis for “chemo brain,” the persistent cognitive impairment experienced by some cancer survivors. A groundbreaking study on rats suggests chemotherapy directly alters gene regulation in key brain areas, offering hope for future targeted therapies.

Gene Disruption Linked to Cognitive Decline

Researchers at The City College of New York (CCNY) have identified how specific chemotherapy drugs impact the brain at a fundamental level. Their findings indicate that the treatment regimen of doxorubicin and cyclophosphamide, commonly used in cancer treatment, significantly boosts the activity of the DNMT3a gene.

This gene plays a critical role in DNA methylation, a process that controls gene expression. The study observed a direct link between elevated DNMT3a and altered DNA methylation patterns within the prefrontal cortex of the rat brain. This region is vital for executive functions such as decision-making and cognitive control.

“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 Co-Lead and Professor of Biology

Unlocking Biological Mechanisms for “Chemo Brain”

This research provides a tangible biological explanation for the long-term cognitive challenges, commonly known as “chemo brain,” that many cancer patients, particularly breast cancer survivors, report even years after completing treatment. The study’s insights could pave the way for identifying vulnerable patients.

Furthermore, the findings may guide the development of novel epigenetic therapies. Interventions targeting DNMT or HDAC enzymes, for instance, could potentially prevent or even reverse chemotherapy-induced cognitive deficits.

The CCNY team is continuing its investigation, focusing on RNA-binding proteins. These proteins are known to influence brain aging and are being examined in the prefrontal cortex and hippocampus of the chemotherapy-treated rats. This ongoing work aims to further elucidate how chemotherapy disrupts molecular pathways associated with cognitive decline.

According to the National Cancer Institute, cognitive impairment can affect up to 75% of cancer patients, with symptoms including memory problems, difficulty concentrating, and reduced processing speed, often persisting long after treatment concludes. This study offers a significant step toward understanding and mitigating these effects.

Future Directions and Collaboration

The research team includes CCNY members Shami Chakrabarti, Chanchal Wagh, Ciara Bagnall-Moreau (also with the Institute of Molecular Medicine, The Feinstein Institute of Medical Research), Fathema Uddin, Joshua Reiser, and Kaliris Salas-Ramirez (CUNY School of Medicine). Collaborators also include Tim Ahles from Memorial Sloan Kettering Cancer Center.