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Sulfatide decrease in myelin influences formation of the paranodal axo‐glial junction and conduction velocity in the sciatic nerve
Author(s) -
Hayashi Akiko,
Kaneko Naoki,
Tomihira Chiaki,
Baba Hiroko
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22447
Subject(s) - myelin , sciatic nerve , biology , peripheral nervous system , nerve conduction velocity , heterozygote advantage , axon , central nervous system , endocrinology , medicine , electrophysiology , white matter , anatomy , neuroscience , biochemistry , genotype , magnetic resonance imaging , radiology , gene
Cerebroside sulfotransferase (CST) catalyzes the production of sulfatide, which is one of the major glycolipids in myelin. Homozygous CST knockout mice were shown to be completely deficient in sulfatide. They were born healthy but began to display progressive neurological deficits from 6 weeks of age. Severe abnormalities of paranodal regions and changes in axonal ion channel distribution were prominent in both the central and peripheral nervous systems. But whether partial decreases in myelin sulfatide levels influence paranodal formation, as well as nerve conduction velocity (NCV), is largely unknown. To determine the functional significance of sulfatide content in myelin, we performed electrophysiological, morphological, and biochemical analyses using heterozygote, homozygote, and wild‐type mouse peripheral nerves and compared the results with individual sulfatide content. NCVs were significantly reduced in homozygote animals compared with wild‐type mice. In contrast, these values were markedly varied in individual heterozygote mice. On the basis of NCV values, we divided heterozygous mice into two groups: mice with mild but significant reduction of NCV and those with normal NCV. Teased nerve fibers obtained from individual mouse sciatic nerves were immunostained, and Na + channel and Caspr cluster lengths were measured to determine abnormal levels of junctional formation at the paranode. Furthermore, sulfatide content in each sciatic nerve was examined by thin layer chromatography. The results demonstrated significant correlations among sulfatide level, severity of paranodal abnormality, and reduction of NCV. Thus, the fine regulation of myelin sulfatide content by CST is important for normal function of myelinated axons. © 2013 Wiley Periodicals, Inc.