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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267729/ https://www.ncbi.nlm.nih.gov/pubmed/34201550 http://dx.doi.org/10.3390/ijms22136718 |
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author | Chen, Yu-Chieh Sheen, Jiunn-Ming Wang, Su-Chen Hsu, Mei-Hsin Hsiao, Chih-Cheng Chang, Kow-Aung Huang, Li-Tung |
author_facet | Chen, Yu-Chieh Sheen, Jiunn-Ming Wang, Su-Chen Hsu, Mei-Hsin Hsiao, Chih-Cheng Chang, Kow-Aung Huang, Li-Tung |
author_sort | Chen, Yu-Chieh |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8267729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82677292021-07-10 Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process Chen, Yu-Chieh Sheen, Jiunn-Ming Wang, Su-Chen Hsu, Mei-Hsin Hsiao, Chih-Cheng Chang, Kow-Aung Huang, Li-Tung Int J Mol Sci Article 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. MDPI 2021-06-23 /pmc/articles/PMC8267729/ /pubmed/34201550 http://dx.doi.org/10.3390/ijms22136718 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Yu-Chieh Sheen, Jiunn-Ming Wang, Su-Chen Hsu, Mei-Hsin Hsiao, Chih-Cheng Chang, Kow-Aung Huang, Li-Tung Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267729/ https://www.ncbi.nlm.nih.gov/pubmed/34201550 http://dx.doi.org/10.3390/ijms22136718 |
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