Histological and Top-Down Proteomic Analyses of the Visual Pathway in the Cuprizone Demyelination Model.
2D gel electrophoresis
Bioinformatics
Mass spectrometry
Multiple sclerosis
Optic nerve
Optic neuritis
Optic tract
Proteoforms
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
02
12
2021
accepted:
07
03
2022
pubmed:
2
6
2022
medline:
9
6
2022
entrez:
1
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35644788
doi: 10.1007/s12031-022-01997-w
pii: 10.1007/s12031-022-01997-w
pmc: PMC9170674
doi:
Substances chimiques
Proteins
0
Cuprizone
5N16U7E0AO
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1374-1401Informations de copyright
© 2022. Crown.
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