A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

• Published in: PloS one 2021-08, Vol.16 (8), p.e0256155-e0256155
• Main Authors: Ahmad, Intakhar, Wergeland, Stig, Oveland, Eystein, Bø, Lars
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Biobanks; Biology and Life Sciences; Biomarkers; Brain - pathology; Brain research; Care and treatment; Cerebral Cortex - pathology; Clinical medicine; Complications and side effects; Corpus callosum; Corpus Callosum - pathology; Cuprizone; Cuprizone - pharmacology; Demyelinating Diseases - pathology; Density; Disease Models, Animal; Female; Gray Matter - pathology; Histopathology; Hospitals; Laboratory animals; Lesions; Markers; Medical records; Medical research; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Multiple sclerosis; Multiple Sclerosis - metabolism; Multiple Sclerosis - physiopathology; Myelin; Myelin Basic Protein - metabolism; Myelin Proteins - analysis; Myelin Proteins - metabolism; Myelin Sheath - metabolism; Myelination; Neurology; Nogo protein; Oligodendrocytes; Oligodendroglia - metabolism; Oligodendroglia - pathology; Patient outcomes; Proteins; Remyelination - physiology; Research and Analysis Methods; Substantia alba; Substantia grisea; White Matter - pathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0256155

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.