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Authors & Affiliations
Niklas Rilke, Mona Shaygan Tabar, Baffour Sarpong, Katharina Lemhoefer, Clarissa Lohmann, Alina Blusch, Anna Meichsner, Zhixiao Wu, Melissa Sgodzai, Adriana Rehm, Pia Renk, Barbara Gisevius, Anna-Lena Fisse, Jeremias Motte, Thomas Grüter, Konstanze Winklhofer, Ralf Gold, Kalliopi Pitarokoili
Abstract
The chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease affecting myelin and neural structures of the PNS. In recent studies, propionic acid (PA) showed anti-inflammatory and disease modifying effects in multiple sclerosis patients. Additionally, PA exerted neuroprotective and neuroregenerative effects in PNS in vitro cell cultures of Schwann cells (SC) and dorsal root ganglia (DRG). In this study, we investigate the potential effects of PA on SC derived from rats sciatic nerve. First, SC were treated with IFNγ to induce MHC-II receptor expression, which was measured via flow cytometric staining. Simultaneously, mRNA expression levels in SC were examined under naïve conditions and after induction of oxidative stress via SNAP (S-Nitroso-N-acetyl-DL-penicillamine). Being exposed to oxidative stress, SC are currently analyzed using Seahorse XF analysis to examine changes in cellular metabolism under the influence of PA. After inducing inflammatory activation in SC with IFNγ, PA displayed anti-inflammatory effects by significantly downregulating the expression of MHC-II receptors after 3 days of PA treatment. Under naïve conditions, SC treated with PA present as pro-myelinating SC via mRNA upregulation of Egr2 and MBP. In a SC co-culture system with adult DRG explants, PA treated SC enhance myelination on DRG neurites. When exposed to SNAP and treated with PA, SC undergo adult phenotype changes into a repair SC phenotype via significant upregulation of c-Jun and Sox2 mRNA. Taken together, these results highlight the emerging potential of PA as a treatment option for CIDP patients as it shows pro-myelinating, anti-oxidative and anti-inflammatory effects on SC.