Histological and Top-Down Proteomic Analyses of the Visual Pathway in the Cuprizone Demyelination Model
| العنوان: | Histological and Top-Down Proteomic Analyses of the Visual Pathway in the Cuprizone Demyelination Model |
|---|---|
| المؤلفون: | Mohammed S. M. Almuslehi, Monokesh K. Sen, Peter J. Shortland, David A. Mahns, Jens R. Coorssen |
| المصدر: | Journal of Molecular Neuroscience. 72:1374-1401 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mice, Inbred C57BL, Proteomics, Cuprizone, Disease Models, Animal, Mice, Cellular and Molecular Neuroscience, Multiple Sclerosis, Animals, Proteins, Visual Pathways, General Medicine |
| الوصف: | A change in visual perception is a frequent early symptom of multiple sclerosis (MS), the pathoaetiology of which remains unclear. Following a slow demyelination process caused by 12 weeks of low-dose (0.1%) cuprizone (CPZ) consumption, histology and proteomics were used to investigate components of the visual pathway in young adult mice. Histological investigation did not identify demyelination or gliosis in the optic tracts, pretectal nuclei, superior colliculi, lateral geniculate nuclei or visual cortices. However, top-down proteomic assessment of the optic nerve/tract revealed a significant change in the abundance of 34 spots in high-resolution two-dimensional (2D) gels. Subsequent liquid chromatography-tandem mass spectrometry (LC-TMS) analysis identified alterations in 75 proteoforms. Literature mining revealed the relevance of these proteoforms in terms of proteins previously implicated in animal models, eye diseases and human MS. Importantly, 24 proteoforms were not previously described in any animal models of MS, eye diseases or MS itself. Bioinformatic analysis indicated involvement of these proteoforms in cytoskeleton organization, metabolic dysregulation, protein aggregation and axonal support. Collectively, these results indicate that continuous CPZ-feeding, which evokes a slow demyelination, results in proteomic changes that precede any clear histological changes in the visual pathway and that these proteoforms may be potential early markers of degenerative demyelinating conditions. |
| تدمد: | 1559-1166 0895-8696 |
| DOI: | 10.1007/s12031-022-01997-w |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db687abde822a814c37b79017d7afa56 https://doi.org/10.1007/s12031-022-01997-w |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....db687abde822a814c37b79017d7afa56 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591166 08958696 |
|---|---|
| DOI: | 10.1007/s12031-022-01997-w |