Institute of Neuroanatomy, Medical Faculty, University of Bonn, 53115 Bonn, Germany.
Institute of Anatomy and Cell Biology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
Int J Mol Sci. 2023 Feb 13;24(4):3716. doi: 10.3390/ijms24043716.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* ≤ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.
多发性硬化症（MS）是一种中枢神经系统（CNS）的炎症性脱髓鞘疾病。虽然目前大多数治疗策略都集中在免疫细胞调节上，但除了药物西尼莫德（siponimod）之外，没有任何治疗干预措施主要针对神经保护和髓鞘再生。最近，尼莫地平（nimodipine）在实验性自身免疫性脑脊髓炎（EAE），即多发性硬化症的小鼠模型中显示出有益的和髓鞘再生作用。尼莫地平还对星形胶质细胞、神经元和成熟少突胶质细胞产生积极影响。在这里，我们研究了 L 型电压门控钙通道拮抗剂尼莫地平对少突胶质前体细胞（OPC）系 Oli-Neu 和原代 OPC 中髓鞘基因和蛋白表达谱的影响。我们的数据表明，尼莫地平对髓鞘相关基因和蛋白表达没有任何影响。此外，尼莫地平处理不会导致这些细胞的任何形态变化。然而，RNA 测序和生物信息学分析鉴定出潜在的 micro（mi）RNA，这些 miRNA 在尼莫地平处理后可能支持髓鞘形成，与二甲基亚砜（DMSO）对照相比。此外，我们用尼莫地平处理斑马鱼，观察到成熟少突胶质细胞数量显著增加（*≤0.05）。综上所述，尼莫地平似乎对 OPC 和成熟少突胶质细胞有不同的积极影响。
