Methotrexate neurotoxicity is related to epigenetic modification of the myelination process

Yu Chieh Chen*, Jiunn Ming Sheen, Su Chen Wang, Mei Hsin Hsu, Chih Cheng Hsiao, Kow Aung Chang, Li Tung Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

11 Scopus citations


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.

Original languageEnglish
Article number6718
JournalInternational Journal of Molecular Sciences
Issue number13
StatePublished - 01 07 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Epigenetic
  • Methotrexate
  • Myelination
  • Neurotrophin


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