Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process
Abstract
:1. Introduction
2. Results
2.1. Methotrexate Treatment Resulted in Altered Myelination-Related Protein mRNA Expression
2.2. Combined Intrathecal and Intraperitoneal Methotrexate Treatment Resulted in an Altered CpG Methylation Status of the BDNF Exon IV Promoter in Both the Brain Cortex and Hippocampus
2.3. Combined Intrathecal and Intraperitoneal Methotrexate Treatment Resulted in Altered CpG Methylation Status of the SOX10 and MBP Promoter in Both Brain Cortex and Hippocampus
2.4. Combined Intrathecal and Intraperitoneal Methotrexate Treatment Resulted in Epigenetic Modification of BDNF Exon IV Promoter, Myelin Basic Protein (MBP) and SOX 10 Promoter
2.5. PRMT1 Is Involved in the Post-Translational Modification of BDNF and Myelination-Related Transcriptomes in MTX-Treated Developing Rats
3. Discussion
4. Material and Methods
4.1. Subjects
4.2. Experimental Procedures
4.3. Brain Tissue Collection
4.4. DNA Bisulfite Modification and Pyrosequencing
4.5. Chromatin Immunoprecipitation (ChIP) Assay for BDNF and Myelination-Related Transcriptomes Modification
4.6. RNA-Protein Immunoprecipitation (RIP) Assay
4.7. Quantitative Real-Time PCR Analysis
4.8. Immunofluorescence Staining
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Forward (5′-3′) | Reverse (5′-3′) Biotinylated | Sequencing Primer |
---|---|---|---|
BDNF exon IV | AGGTAGAGGAGGTATTATATGATAGT AGGTAGAGGAGGTATTATATGATAGT | ACTATATATTTCCCCTTCTCTTCAATT AACTCTTACTATATATTTCCCCTTCT | AGGAGGTATTATATGATAGTT ATTTATAGAGGAGAGGATTGT |
MBP | GAGATAGTTAGTTTAAGATTTTAGGAAGAA | ACCCTACCAATTATTCTTTAAATCTACT | GTTAGTTTAAGATTTTAGGAAGAAA |
SOX10 | GTTAGGTAAGGTAGATTTTAAAAGGGATG | TAACCACAACCAAAACACTACTCAA | GTAGATTTTAAAAGGGATGG ATGTGATTGAGTTGGAT |
Forward 5′-3′ | Reverse 5′-3′ | |
---|---|---|
BDNF exon IV promoter | TGACAGCTCACGTCAAGGCA | ATCTAGGCAGAGACTGGGAGAT |
MBP promoter | AGCTAGTTCAAGACCCCAGG | AGATATGAATGTGGGCCTGTGC |
SOX10 promoter | CAGCCATGAGGTAATGTCCA | GTAGCCAGCTGCCGAGTAG |
Forward 5′-3′ | Reverse 5′-3′ | |
---|---|---|
BDNF exon IV | ATTCACCGAGGAGAGGACTG | AGTCTTTGGTGGCCGATATG |
MBP | CTCTGGCAAGG CTCACACAC | TCTGCTGAGGGACAGGCCTCTC |
SOX10 | TACAAGTACCAACCTCGGCG | CATGGGGGAGCCTTCTTCTG |
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Chen, Y.-C.; Sheen, J.-M.; Wang, S.-C.; Hsu, M.-H.; Hsiao, C.-C.; Chang, K.-A.; Huang, L.-T. Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process. Int. J. Mol. Sci. 2021, 22, 6718. https://doi.org/10.3390/ijms22136718
Chen Y-C, Sheen J-M, Wang S-C, Hsu M-H, Hsiao C-C, Chang K-A, Huang L-T. Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process. International Journal of Molecular Sciences. 2021; 22(13):6718. https://doi.org/10.3390/ijms22136718
Chicago/Turabian StyleChen, Yu-Chieh, Jiunn-Ming Sheen, Su-Chen Wang, Mei-Hsin Hsu, Chih-Cheng Hsiao, Kow-Aung Chang, and Li-Tung Huang. 2021. "Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process" International Journal of Molecular Sciences 22, no. 13: 6718. https://doi.org/10.3390/ijms22136718