Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain
Abstract Chemotherapy can cause several long-term side effects that can affect cancer survivors’ quality of life-, notably cognitive decline in response to select chemotherapeutic agents. Studies using both human patients and animal models have been employed to determine the regions of the brain tha...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-07419-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238590456856576 |
|---|---|
| author | Shami Chakrabarti Chanchal Wagh Ciara Bagnall-Moreau Fathema Uddin Joshua Reiser Kaliris Salas-Ramirez Tim Ahles Karen Hubbard |
| author_facet | Shami Chakrabarti Chanchal Wagh Ciara Bagnall-Moreau Fathema Uddin Joshua Reiser Kaliris Salas-Ramirez Tim Ahles Karen Hubbard |
| author_sort | Shami Chakrabarti |
| collection | DOAJ |
| description | Abstract Chemotherapy can cause several long-term side effects that can affect cancer survivors’ quality of life-, notably cognitive decline in response to select chemotherapeutic agents. Studies using both human patients and animal models have been employed to determine the regions of the brain that are subject to the most considerable changes, furthermore, elucidating possible molecular mechanisms of chemotherapy-induced cognitive impairment (CICI). However, the reason behind the differences in symptoms and duration of CICI between patients have yet to be identified. This study focused on understanding whether the systemic delivery of doxorubicin and cyclophosphamide (AC chemotherapeutics) causes any epigenetic factors to change in the female rat prefrontal cortex (PFC), possibly providing an insight into the variability of clinical manifestations of CICI. We evaluated DNA methylation levels and patterns in the PFC after AC-chemotherapy administration. We also demonstrated changes in histone deacetylase and acetyl transferase activity levels in the murine PFC in response to treatment. Despite no change in the global DNA methylation level, we found that several genes related to neuronal development and maintenance were differentially methylated in the promoter and exon regions in the rat PFC. Our study showed a significant increase in the expression of the de novo DNA methyl transferase DNMT3a compared to the control. |
| format | Article |
| id | doaj-art-08a624783251464f9e53e166ecf3bc1e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-08a624783251464f9e53e166ecf3bc1e2025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-07419-2Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brainShami Chakrabarti0Chanchal Wagh1Ciara Bagnall-Moreau2Fathema Uddin3Joshua Reiser4Kaliris Salas-Ramirez5Tim Ahles6Karen Hubbard7Department of Biology, The City College of New YorkDepartment of Biology, The City College of New YorkDepartment of Biology, The City College of New YorkDepartment of Biology, The City College of New YorkDepartment of Biology, The City College of New YorkDepartment of Molecular, Cellular and Biomedical Sciences, CUNY School of MedicineDepartment of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer CenterDepartment of Biology, The City College of New YorkAbstract Chemotherapy can cause several long-term side effects that can affect cancer survivors’ quality of life-, notably cognitive decline in response to select chemotherapeutic agents. Studies using both human patients and animal models have been employed to determine the regions of the brain that are subject to the most considerable changes, furthermore, elucidating possible molecular mechanisms of chemotherapy-induced cognitive impairment (CICI). However, the reason behind the differences in symptoms and duration of CICI between patients have yet to be identified. This study focused on understanding whether the systemic delivery of doxorubicin and cyclophosphamide (AC chemotherapeutics) causes any epigenetic factors to change in the female rat prefrontal cortex (PFC), possibly providing an insight into the variability of clinical manifestations of CICI. We evaluated DNA methylation levels and patterns in the PFC after AC-chemotherapy administration. We also demonstrated changes in histone deacetylase and acetyl transferase activity levels in the murine PFC in response to treatment. Despite no change in the global DNA methylation level, we found that several genes related to neuronal development and maintenance were differentially methylated in the promoter and exon regions in the rat PFC. Our study showed a significant increase in the expression of the de novo DNA methyl transferase DNMT3a compared to the control.https://doi.org/10.1038/s41598-025-07419-2Chemotherapy-induced cognitive impairmentEpigeneticsDNA methylationHistone acetyl transferaseHistone deacetylasePrefrontal cortex |
| spellingShingle | Shami Chakrabarti Chanchal Wagh Ciara Bagnall-Moreau Fathema Uddin Joshua Reiser Kaliris Salas-Ramirez Tim Ahles Karen Hubbard Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain Scientific Reports Chemotherapy-induced cognitive impairment Epigenetics DNA methylation Histone acetyl transferase Histone deacetylase Prefrontal cortex |
| title | Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain |
| title_full | Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain |
| title_fullStr | Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain |
| title_full_unstemmed | Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain |
| title_short | Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain |
| title_sort | chemotherapy treatment alters dna methylation patterns in the prefrontal cortex of female rat brain |
| topic | Chemotherapy-induced cognitive impairment Epigenetics DNA methylation Histone acetyl transferase Histone deacetylase Prefrontal cortex |
| url | https://doi.org/10.1038/s41598-025-07419-2 |
| work_keys_str_mv | AT shamichakrabarti chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT chanchalwagh chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT ciarabagnallmoreau chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT fathemauddin chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT joshuareiser chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT kalirissalasramirez chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT timahles chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain AT karenhubbard chemotherapytreatmentaltersdnamethylationpatternsintheprefrontalcortexoffemaleratbrain |