Schwann Cell Support as a Novel Approach to Peripheral Nervous System Demyelinating Disease
JSHS · 2022
Overview
Peripheral nervous system (PNS) degenerative diseases are characterized by nerve impulse conduction anomalies and neurodegeneration. Demyelination, a degenerative process that erodes away the myelin sheath which protects neurons, is often the underlying cause. Myelin production is orchestrated by Schwann Cells (SC), which wrap around nerve axons to produce myelin. However, current PNS disease treatment focuses on the neuron, not the SC, with the goal of immunosuppression. Additionally, PNS degenerative disease drugs can have severe adverse effects. This research aimed to treat demyelination in PNS degenerative diseases by targeting SCs non-invasively. This approach is based on studies demonstrating that patients with demyelinating diseases have decreased blood serum ascorbic acid levels. Therefore, this research examined the relationship between exogenous ascorbic acid application and the SC’s potential to myelinate neuronal axons in PNS degenerative disease. Employing an in vitro SC-neuronal cell demyelination co-culture model, it was found that ascorbic acid application increases SC myelin production as a treatment (210%) and as prevention (222%), reduces SC oxidative stress, and increases ECM signaling and remodeling molecules. In silico, gene set enrichment and ontology analysis corroborated these in vitro findings, revealing a deeper understanding of mechanism. Furthermore, a regression model was developed from in vitro data predicting likelihood of developing a PNS degenerative disease (adjusted R² of 0.945) based on potential SC biomarkers which can be measured non- invasively. Overall, data suggests ascorbic acid as a potential neoadjuvant and adjunct treatment in PNS degenerative diseases and suggests mechanism in a novel approach of targeting the SC.
Competition history
- JSHS 2022
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