Abstract
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.
Highlights
Multiple Sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system (CNS) leading to neuronal damage resulting in functional disability.Remyelination is the natural regenerating process of demyelinated nerves and frequently occurs after demyelinating events in all manifestations of the disease [1,2,3,4,5]
Animals treated with CDP-choline in different doses (500, 100, and 50 mg/kg body weight) showed significantly higher re-expression of myelin protein myelin proteolipid protein (PLP) (Figure 1A, p = 0.003)
Similar results were found by analyzing the histochemical luxol-fast blue (LFB) staining of myelination (Figure 1B) and MBP stained myelin (Figure 1E–H1)
Summary
Remyelination is the natural regenerating process of demyelinated nerves and frequently occurs after demyelinating events in all manifestations of the disease [1,2,3,4,5]. This repair process is not an invariant response to demyelination and is often incomplete or even fails in MS patients [6,7]. Numerous animal studies provided several lines of evidence that remyelination could protect axons from degradation and might lead to functional recovery and restoration of axonal conduction velocity [14,15,16]
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