Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination
Inflammatory attacks and demyelination in the central nervous system (CNS) are the key factors responsible for the damage of neurons in multiple sclerosis (MS). Remyelination is the natural regenerating process after demyelination that also provides neuroprotection but is often incomplete or fails i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/11/1156 |
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| author | Viktoria Gudi Nora Schäfer Stefan Gingele Martin Stangel Thomas Skripuletz |
| author_facet | Viktoria Gudi Nora Schäfer Stefan Gingele Martin Stangel Thomas Skripuletz |
| author_sort | Viktoria Gudi |
| collection | DOAJ |
| description | Inflammatory attacks and demyelination in the central nervous system (CNS) are the key factors responsible for the damage of neurons in multiple sclerosis (MS). Remyelination is the natural regenerating process after demyelination that also provides neuroprotection but is often incomplete or fails in MS. Currently available therapeutics are affecting the immune system, but there is no substance that might enhance remyelination. Cytidine-S-diphosphate choline (CDP-choline), a precursor of the biomembrane component phospholipid phosphatidylcholine was shown to improve remyelination in two animal models of demyelination. However, the doses used in previous animal studies were high (500 mg/kg), and it is not clear if lower doses, which could be applied in human trials, might exert the same beneficial effect on remyelination. The aim of this study was to confirm previous results and to determine the potential regenerative effects of lower doses of CDP-choline (100 and 50 mg/kg). The effects of CDP-choline were investigated in the toxic cuprizone-induced mouse model of de- and remyelination. We found that even low doses of CDP-choline effectively enhanced early remyelination. The beneficial effects on myelin regeneration were accompanied by higher numbers of oligodendrocytes. In conclusion, CDP-choline could become a promising regenerative substance for patients with multiple sclerosis and should be tested in a clinical trial. |
| first_indexed | 2024-03-10T05:09:51Z |
| format | Article |
| id | doaj.art-4c1c590b6af54b23a2625ad0b0e2d666 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T05:09:51Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-4c1c590b6af54b23a2625ad0b0e2d6662023-11-23T00:56:03ZengMDPI AGPharmaceuticals1424-82472021-11-011411115610.3390/ph14111156Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and RemyelinationViktoria Gudi0Nora Schäfer1Stefan Gingele2Martin Stangel3Thomas Skripuletz4Department of Neurology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neurology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neurology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neurology, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neurology, Hannover Medical School, 30625 Hannover, GermanyInflammatory attacks and demyelination in the central nervous system (CNS) are the key factors responsible for the damage of neurons in multiple sclerosis (MS). Remyelination is the natural regenerating process after demyelination that also provides neuroprotection but is often incomplete or fails in MS. Currently available therapeutics are affecting the immune system, but there is no substance that might enhance remyelination. Cytidine-S-diphosphate choline (CDP-choline), a precursor of the biomembrane component phospholipid phosphatidylcholine was shown to improve remyelination in two animal models of demyelination. However, the doses used in previous animal studies were high (500 mg/kg), and it is not clear if lower doses, which could be applied in human trials, might exert the same beneficial effect on remyelination. The aim of this study was to confirm previous results and to determine the potential regenerative effects of lower doses of CDP-choline (100 and 50 mg/kg). The effects of CDP-choline were investigated in the toxic cuprizone-induced mouse model of de- and remyelination. We found that even low doses of CDP-choline effectively enhanced early remyelination. The beneficial effects on myelin regeneration were accompanied by higher numbers of oligodendrocytes. In conclusion, CDP-choline could become a promising regenerative substance for patients with multiple sclerosis and should be tested in a clinical trial.https://www.mdpi.com/1424-8247/14/11/1156multiple sclerosisCDP-cholinecuprizonemicrogliaastrocytesoligodendrocytes |
| spellingShingle | Viktoria Gudi Nora Schäfer Stefan Gingele Martin Stangel Thomas Skripuletz Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination Pharmaceuticals multiple sclerosis CDP-choline cuprizone microglia astrocytes oligodendrocytes |
| title | Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination |
| title_full | Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination |
| title_fullStr | Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination |
| title_full_unstemmed | Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination |
| title_short | Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination |
| title_sort | regenerative effects of cdp choline a dose dependent study in the toxic cuprizone model of de and remyelination |
| topic | multiple sclerosis CDP-choline cuprizone microglia astrocytes oligodendrocytes |
| url | https://www.mdpi.com/1424-8247/14/11/1156 |
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