Nimodipine Exerts Beneficial Effects on the Rat Oligodendrocyte Cell Line OLN-93.
Felix BoltzMichael EndersAndreas FeigenspanPhilipp KirchnerArif Bülent EkiciStefanie KuertenPublished in: Brain sciences (2022)
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). Therapy is currently limited to drugs that interfere with the immune system; treatment options that primarily mediate neuroprotection and prevent neurodegeneration are not available. Here, we studied the effects of nimodipine on the rat cell line OLN-93, which resembles young mature oligodendrocytes. Nimodipine is a dihydropyridine that blocks the voltage-gated L-type calcium channel family members Ca v 1.2 and Ca v 1.3. Our data show that the treatment of OLN-93 cells with nimodipine induced the upregulation of myelin genes, in particular of proteolipid protein 1 ( Plp1 ), which was confirmed by a significantly greater expression of PLP1 in immunofluorescence analysis and the presence of myelin structures in the cytoplasm at the ultrastructural level. Whole-genome RNA sequencing additionally revealed the upregulation of genes that are involved in neuroprotection, remyelination, and antioxidation pathways. Interestingly, the observed effects were independent of Ca v 1.2 and Ca v 1.3 because OLN-93 cells do not express these channels, and there was no measurable response pattern in patch-clamp analysis. Taking into consideration previous studies that demonstrated a beneficial effect of nimodipine on microglia, our data support the notion that nimodipine is an interesting drug candidate for the treatment of MS and other demyelinating diseases.
Keyphrases
- subarachnoid hemorrhage
- multiple sclerosis
- brain injury
- induced apoptosis
- cerebral ischemia
- poor prognosis
- white matter
- drug induced
- cell cycle arrest
- protein kinase
- signaling pathway
- electronic health record
- genome wide
- ms ms
- big data
- emergency department
- endoplasmic reticulum stress
- high glucose
- machine learning
- long non coding rna
- binding protein
- replacement therapy
- data analysis
- combination therapy
- spinal cord injury
- mesenchymal stem cells
- endothelial cells
- deep learning
- cerebrospinal fluid