Novel forms of neurofascin 155 in the central nervous system: alterations in paranodal disruption models and multiple sclerosis
| Autor: | Seema M. Shroff, Matthew N. Rasband, Manzoor A. Bhat, Jeffrey L. Dupree, Carmen Sato-Bigbee, Babette Fuss, Anthony D. Pomicter, Peter J. Brophy |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Null mice
Adult Central Nervous System Male Multiple Sclerosis Central nervous system Biology Central nervous system disease Rats Sprague-Dawley 03 medical and health sciences Myelin Mice 0302 clinical medicine medicine Animals Humans Protein Isoforms Nerve Growth Factors Axon 030304 developmental biology Aged Aged 80 and over Mice Knockout 0303 health sciences Multiple sclerosis Original Articles Middle Aged medicine.disease Cell biology Rats Sprague dawley Disease Models Animal medicine.anatomical_structure Knockout mouse Female Neurology (clinical) Neuroscience Cell Adhesion Molecules 030217 neurology & neurosurgery |
| Zdroj: | Brain; Vol 133 |
| DOI: | 10.17615/jj0a-gj67 |
| Popis: | Stability of the myelin-axon unit is achieved, at least in part, by specialized paranodal junctions comprised of the neuronal heterocomplex of contactin and contactin-associated protein and the myelin protein neurofascin 155. In multiple sclerosis, normal distribution of these proteins is altered, resulting in the loss of the insulating myelin and consequently causing axonal dysfunction. Previously, this laboratory reported that mice lacking the myelin-enriched lipid sulphatide are characterized by a progressive deterioration of the paranodal structure. Here, it is shown that this deterioration is preceded by significant loss of neurofascin 155 clustering at the myelin paranode. Interestingly, prolonged electrophoretic separation revealed the existence of two neurofascin 155 bands, neurofascin 155 high and neurofascin 155 low, which are readily observed following N-linked deglycosylation. Neurofascin 155 high is observed at 7 days of age and reaches peak expression at one month of age, while neurofascin 155 low is first observed at 14 days of age and constantly increases until 5 months of age. Studies using conditional neurofascin knockout mice indicated that neurofascin 155 high and neurofascin 155 low are products of the neurofascin gene and are exclusively expressed by oligodendrocytes within the central nervous system. Neurofascin 155 high is a myelin paranodal protein while the distribution of neurofascin 155 low remains to be determined. While neurofascin 155 high levels are significantly reduced in the sulphatide null mice at 15 days, 30 days and 4 months of age, neurofascin 155 low levels remain unaltered. Although maintained at normal levels, neurofascin 155 low is incapable of preserving paranodal structure, thus indicating that neurofascin 155 high is required for paranodal stability. Additionally, comparisons between neurofascin 155 high and neurofascin 155 low in human samples revealed a significant alteration, specifically in multiple sclerosis plaques. |
| Databáze: | OpenAIRE |
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