Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process
With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurol...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/13/6718 |
| _version_ | 1797529061042421760 |
|---|---|
| author | Yu-Chieh Chen Jiunn-Ming Sheen Su-Chen Wang Mei-Hsin Hsu Chih-Cheng Hsiao Kow-Aung Chang Li-Tung Huang |
| author_facet | Yu-Chieh Chen Jiunn-Ming Sheen Su-Chen Wang Mei-Hsin Hsu Chih-Cheng Hsiao Kow-Aung Chang Li-Tung Huang |
| author_sort | Yu-Chieh Chen |
| collection | DOAJ |
| description | With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways. |
| first_indexed | 2024-03-10T10:08:07Z |
| format | Article |
| id | doaj.art-07d10dc3080e4e6e89661be8075315df |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:08:07Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-07d10dc3080e4e6e89661be8075315df2023-11-22T01:20:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213671810.3390/ijms22136718Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination ProcessYu-Chieh Chen0Jiunn-Ming Sheen1Su-Chen Wang2Mei-Hsin Hsu3Chih-Cheng Hsiao4Kow-Aung Chang5Li-Tung Huang6Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanWith the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways.https://www.mdpi.com/1422-0067/22/13/6718methotrexateneurotrophinmyelinationepigenetic |
| spellingShingle | Yu-Chieh Chen Jiunn-Ming Sheen Su-Chen Wang Mei-Hsin Hsu Chih-Cheng Hsiao Kow-Aung Chang Li-Tung Huang Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process International Journal of Molecular Sciences methotrexate neurotrophin myelination epigenetic |
| title | Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process |
| title_full | Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process |
| title_fullStr | Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process |
| title_full_unstemmed | Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process |
| title_short | Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process |
| title_sort | methotrexate neurotoxicity is related to epigenetic modification of the myelination process |
| topic | methotrexate neurotrophin myelination epigenetic |
| url | https://www.mdpi.com/1422-0067/22/13/6718 |
| work_keys_str_mv | AT yuchiehchen methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess AT jiunnmingsheen methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess AT suchenwang methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess AT meihsinhsu methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess AT chihchenghsiao methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess AT kowaungchang methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess AT litunghuang methotrexateneurotoxicityisrelatedtoepigeneticmodificationofthemyelinationprocess |