Chemotherapy Cognitive Changes Rats Study
Chemotherapy Linked to Lasting Cognitive Changes in Rats, Offering Clues to “Chemo Brain”
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New York, NY – researchers at The City College of New York (CCNY) have uncovered a critically important molecular link between chemotherapy treatment and enduring cognitive impairments in rats, possibly shedding light on the persistent “chemo brain” experienced by many cancer survivors. The groundbreaking study, published in Nature: Scientific Reports, identifies specific changes in gene regulation within the brain’s prefrontal cortex following chemotherapy.
Unraveling the Molecular Basis of Cognitive Decline
The study, titled “Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain,” utilized an animal model to investigate the impact of chemotherapy at a molecular level. ”Our study explored how chemotherapy affects the brain at the molecular level using an animal model,” explained Karen Hubbard, professor of biology in CCNY’s Division of Science and a co-lead author of the study. “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.”
For the first time, the CCNY team demonstrated that a common chemotherapy regimen, consisting of doxorubicin and cyclophosphamide, considerably elevates the expression of DNMT3a. this gene plays a crucial role in adding methylation marks to DNA, a process known as DNA methylation. The researchers observed that these alterations in DNMT3a expression were associated with modified DNA methylation patterns in key brain regions. This molecular disruption is hypothesized to be a primary driver behind the long-term cognitive issues, often referred to as “chemo brain,” that many cancer patients report.
Implications for Cancer Survivors and Future Therapies
The findings offer a tangible biological explanation for the cognitive difficulties that many cancer survivors, especially those treated for breast cancer, continue to experience long after their treatment concludes. This research holds significant promise for improving the quality of life for these individuals.
“This study offers a biological explanation for these cognitive problems that many cancer survivors, especially breast cancer patients, report long after treatment ends,” Hubbard elaborated.
The implications of this research extend to the advancement of novel therapeutic strategies. By identifying vulnerable patients and the specific molecular pathways affected, clinicians may be able to:
Identify high-Risk Patients: Pinpoint individuals most susceptible to developing cognitive side effects from chemotherapy.
Guide Targeted Therapies: Inform the creation of specialized epigenetic therapies, such as inhibitors of DNMT or HDAC (histone deacetylase), which coudl potentially prevent or even reverse chemotherapy-induced cognitive decline.
Ongoing Research and Future Directions
The research team at CCNY is continuing its examination, with a current focus on understanding the role of RNA-binding proteins.These proteins are known to be involved in brain aging and are being examined in both the prefrontal cortex and hippocampus of their chemotherapy-treated animal models. “This work aims to further uncover how chemotherapy disrupts molecular pathways linked to cognitive decline,” stated Hubbard.
The collaborative effort involved several researchers from CCNY, including Shami Chakrabarti, Chanchal Wagh, Ciara Bagnall-Moreau (also affiliated with the Institute of Molecular Medicine, The Feinstein Institute of Medical Research), Fathema Uddin, Joshua reiser, and Kaliris Salas-ramirez (CUNY School of Medicine). Additional contributions were made by Tim Ahles from Memorial Sloan kettering Cancer Center.Source:
Journal reference: Chakrabarti, S., et al. (2025) Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain. Scientific Reports. doi.org/10.1038/s41598-025-07419-2