Axotomy does not up-regulate expression of sodium channel Na(v)1.8 in Purkinje cells.
Aberrant expression of the sensory neuron specific (SNS) sodium channel Na(v)1.8 has been demonstrated in cerebellar Purkinje cells in experimental models of multiple sclerosis (MS) and in human MS. The aberrant expression of Na(v)1.8, which is normally present in primary sensory neurons but not in the CNS, may perturb cerebellar function, but the mechanisms that trigger it are not understood. Because axotomy can provoke changes in Na(v)1.8 expression in dorsal root ganglion (DRG) neurons, we tested the hypothesis that axotomy can provoke an up-regulation of Na(v)1.8 expression in Purkinje cells, using a surgical model that transects axons of Purkinje cells in lobules IIIb-VII in the rat. In situ hybridization and immunocytochemistry did not reveal an up-regulation of Na(v)1.8 mRNA or protein in axotomized Purkinje cells. Hybridization and immunostaining signals for the sodium channel Na(v)1.6 were clearly present, demonstrating that sodium channel transcripts and protein were present in experimental cerebella. These results demonstrate that axotomy does not trigger the expression of Na(v)1.8 in Purkinje cells.
Black
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JA
Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, CT 06510, USA. joel.black@yale.edu
Dusart
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Sotelo
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Waxman
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D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D019771:Axotomy; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D012333:RNA, Messenger; C568317:SCN10A protein, human; C568319:Scn10a protein, rat; D015222:Sodium Channels; D029961:Zebrafish Proteins; C430124:scn8ab protein, zebrafish