rHIgM22 enhances remyelination in the brain of the cuprizone mouse model of demyelination
| Autor: | Jing Wang, Charlene Cui, Yu Wang, Ariana P. Mullin, Erika L. Troy, Raymond W. Colburn, Tom J. Parry, Elias Pavlopoulos, Anthony O. Caggiano |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Monoamine Oxidase Inhibitors Receptor Platelet-Derived Growth Factor alpha Time Factors Corpus callosum Central nervous system lcsh:RC321-571 Mice 03 medical and health sciences Cuprizone 0302 clinical medicine Immune system medicine Animals Remyelination lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Myelin Sheath Analysis of Variance biology Oligodendrocytes Multiple sclerosis Cell Differentiation Myelin Basic Protein Optic Nerve Oligodendrocyte Transcription Factor 2 medicine.disease Spinal cord Isotype Mice Inbred C57BL Disease Models Animal Oligodendroglia 030104 developmental biology medicine.anatomical_structure Immunoglobulin M Neurology biology.protein rHIgM22 Antibody Demyelination Neuroscience 030217 neurology & neurosurgery Demyelinating Diseases |
| Zdroj: | Neurobiology of Disease, Vol 105, Iss, Pp 142-155 (2017) |
| Popis: | Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal. Previous studies have shown that a recombinant human-derived monoclonal IgM antibody, designated rHIgM22, promotes remyelination, particularly of the spinal cord in rodent models of demyelination. Here, we examined the effects of rHIgM22 in remyelination in the brain using the mouse model of cuprizone-induced demyelination, which is characterized by spontaneous remyelination. The myelination state of the corpus callosum of cuprizone-fed mice treated with rHIgM22 was examined immediately after the end of the cuprizone diet as well as at different time points during the recovery period with regular food, and compared with that of cuprizone-fed animals treated with either vehicle or human IgM isotype control antibody. Mice fed only regular food were used as controls. We demonstrate that treatment with rHIgM22 accelerated remyelination of the demyelinated corpus callosum. The remyelination-enhancing effects of rHIgM22 were found across different, anatomically distinct regions of the corpus callosum, and followed a spatiotemporal pattern that was similar to that of the spontaneous remyelination process. These enhancing effects were also accompanied by increased differentiation of OPCs into mature oligodendrocytes. Our data indicate strong remyelination-promoting capabilities of rHIgM22 and further support its therapeutic potential in MS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|