Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells

被引:2
|
作者
Enders, Michael [1 ,2 ]
Weier, Alicia [1 ,2 ]
Chunder, Rittika [1 ]
An, Young [1 ]
Bremm, Franziska [3 ]
Feigenspan, Andreas [3 ]
Buettner, Christian [4 ]
Ekici, Arif Buelent [4 ]
Mingardo, Enrico [5 ]
Odermatt, Benjamin [1 ]
Kuerten, Stefanie [1 ,2 ]
机构
[1] Univ Bonn, Inst Neuroanat, Med Fac, D-53115 Bonn, Germany
[2] Univ Erlangen Nurnberg, Inst Anat & Cell Biol, D-91054 Erlangen, Germany
[3] Univ Erlangen Nurnberg, Dept Biol, Anim Physiol, D-91058 Erlangen, Germany
[4] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany
[5] Univ Bonn, Inst Anat & Cell Biol, Med Fac, D-53115 Bonn, Germany
关键词
dihydropyridines; nimodipine; MS; myelination; neuroprotection; Oli-Neu; OPC; zebrafish; MULTIPLE-SCLEROSIS; NERVOUS-SYSTEM; IN-VITRO; NOGO-A; MYELINATION; EXPRESSION; BRAIN; METALLOTHIONEIN; REGENERATION; IMPROVES;
D O I
10.3390/ijms24043716
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (* p <= 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.
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页数:21
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