| Sodium-dependent vitamin C transporter 2 deficiency causes hypomyelination and extracellular matrix defects in the peripheral nervous system. | |
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MedLine Citation:
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PMID: 22114285 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Ascorbic acid (vitamin C) is necessary for myelination of Schwann cell/neuron cocultures and has shown beneficial effects in the treatment of a Charcot-Marie-Tooth neuropathy 1A (CMT1A) mouse model. Although clinical studies revealed that ascorbic acid treatment had no impact on CMT1A, it is assumed to have an important function in peripheral nerve myelination and possibly in remyelination. However, the transport pathway of ascorbic acid into peripheral nerves and the mechanism of ascorbic acid function in peripheral nerves in vivo remained unclear. In this study, we used sodium-dependent vitamin C transporter 2-heterozygous (SVCT2(+/-)) mice to elucidate the functions of SVCT2 and ascorbic acid in the murine peripheral nervous system. SVCT2 and ascorbic acid levels were reduced in SVCT2(+/-) peripheral nerves. Morphometry of sciatic nerve fibers revealed a decrease in myelin thickness and an increase in G-ratios in SVCT2(+/-) mice. Nerve conduction velocities and sensorimotor performance in functional tests were reduced in SVCT2(+/-) mice. To investigate the mechanism of ascorbic acid function, we studied the expression of collagens in the extracellular matrix of peripheral nerves. Here, we show that expression of various collagen types was reduced in sciatic nerves of SVCT2(+/-) mice. We found that collagen gene transcription was reduced in SVCT2(+/-) mice but hydroxyproline levels were not, indicating that collagen formation was regulated on the transcriptional and not the posttranslational level. These results help to clarify the transport pathway and mechanism of action of ascorbic acid in the peripheral nervous system and may lead to novel therapeutic approaches to peripheral neuropathies by manipulation of SVCT2 function. |
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Authors:
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Burkhard Gess; Dominik Röhr; Robert Fledrich; Michael W Sereda; Ilka Kleffner; Anne Humberg; Johanna Nowitzki; Jan-Kolja Strecker; Hartmut Halfter; Peter Young |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 31 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 17180-92 Citation Subset: IM |
Affiliation:
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Departments of Neurology and Biology, University of Münster, 48149 Münster, Germany, Department of Neurogenetics, Max-Planck Institute for Experimental Medicine, 37075 Göttingen, Germany, and Department of Clinical Neurophysiology, University of Göttingen, 37075 Göttingen, Germany. |
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