Function of Sodium-dependent Vitamin C Transporter 2 in myelination, myelin-maintenance and neuroprotection in the peripheral nervous system

• Applicant: Dr. Burkhard Gess
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 183994089

Although ascorbic acid has a known effect on myelination in vitro and in vivo, the knowledge of mechanisms and dynamics of ascorbic acid transport into peripheral nerves is scarce. For that reason, we analyzed the expression and activity of Sodium-dependent Vitamin C Transporters 1 and 2 (SVCT1 and 2) in the PNS. SVCT2 was highly expressed in Schwann cell domains of uncompacted myelin as well as in axons, whereas SVCT1 was expressed at much lower levels confined to the axons. We showed that SVCT2 was necessary for the uptake of ascorbic acid into cultured Schwann cells. The functional relevance of the Vitamin C transporters on myelination, myelin maintenance and Schwann cell biology was not analyzed so far. Thus we plan to study the function of SVCT2 in myelination, myelin-maintenance and neuroprotection in the PNS. In vitro coculture models will be employed to study the function of SVCT2 in early steps of Schwann cellaxon alignment and myelination. Transgenic overexpression and knock-out mouse models will be used to study the role of SVCT2 in myelination, myelin-maintenance and extracellular matrix formation in vivo. To further analyze the function of SVCTs in vivo cross-breeding experiments with PMP22 mutant mouse models for demyelinating neuropathies will be conducted to assess a potential regenerative and even neuroprotective effect of SVCT2 in demyelinating neuropathies.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Peter Young