Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments
Axonal damage is considered the major cause of irreversible disability in multiple sclerosis (MS). Which mechanisms underlie the damage and whether this is secondary to myelin damage remains to be clarified. Recently, we have demonstrated that autoimmunity to the axonal/neuronal cytoskeletal protein...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996108001952 |
| _version_ | 1818615679645908992 |
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| author | Ruth Huizinga Wouter Gerritsen Nicole Heijmans Sandra Amor |
| author_facet | Ruth Huizinga Wouter Gerritsen Nicole Heijmans Sandra Amor |
| author_sort | Ruth Huizinga |
| collection | DOAJ |
| description | Axonal damage is considered the major cause of irreversible disability in multiple sclerosis (MS). Which mechanisms underlie the damage and whether this is secondary to myelin damage remains to be clarified. Recently, we have demonstrated that autoimmunity to the axonal/neuronal cytoskeletal protein neurofilament light (NF-L) induces axonal damage and neurological disease including spasticity — a common feature of MS. To examine the relationship between axonal damage and demyelination we have characterized the detailed neuropathology of NF-L-induced disease in Biozzi mice compared to classical experimental autoimmune encephalomyelitis (EAE) induced with myelin oligodendrocyte glycoprotein (MOG).In NF-L-induced neurological disease the lesions were predominantly located in the dorsal column displaying extensive axonal degeneration, but were also abundant in the gray matter. In contrast, lesions in MOG-EAE were restricted to the lateral and ventral columns and displayed less axonal damage and little gray matter involvement. The differential lesion location was confirmed by quantitation of leukocyte subsets. In both diseases myelin damage was a common feature although the numerous empty myelin sheaths in NF-L-disease indicative of axonal damage suggest that myelin damage was a secondary event.In summary, autoimmunity to NF-L induces a distinct lesion topology, axonal damage and gray matter lesions supporting the notion that axonal loss and gray matter pathology can be the direct consequence of a primary autoimmune attack against axonal antigens such as NF-L rather than merely a secondary event to myelin damage. |
| first_indexed | 2024-12-16T16:37:45Z |
| format | Article |
| id | doaj.art-cd0322953f6f45aa8f14acee0fdfcb0b |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:37:45Z |
| publishDate | 2008-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-cd0322953f6f45aa8f14acee0fdfcb0b2022-12-21T22:24:25ZengElsevierNeurobiology of Disease1095-953X2008-12-01323461470Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilamentsRuth Huizinga0Wouter Gerritsen1Nicole Heijmans2Sandra Amor3Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The NetherlandsDepartment of Pathology, VU University Medical Center and MS Center, Amsterdam, The NetherlandsDepartment of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The NetherlandsDepartment of Pathology, VU University Medical Center and MS Center, Amsterdam, The Netherlands; Neuroimmunology Unit, Neuroscience Centre, Institute of Cell and Molecular Science, Queen Mary University of London, UK; Corresponding author. Department of Pathology, MS Center, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Fax: +31 20 444 2964.Axonal damage is considered the major cause of irreversible disability in multiple sclerosis (MS). Which mechanisms underlie the damage and whether this is secondary to myelin damage remains to be clarified. Recently, we have demonstrated that autoimmunity to the axonal/neuronal cytoskeletal protein neurofilament light (NF-L) induces axonal damage and neurological disease including spasticity — a common feature of MS. To examine the relationship between axonal damage and demyelination we have characterized the detailed neuropathology of NF-L-induced disease in Biozzi mice compared to classical experimental autoimmune encephalomyelitis (EAE) induced with myelin oligodendrocyte glycoprotein (MOG).In NF-L-induced neurological disease the lesions were predominantly located in the dorsal column displaying extensive axonal degeneration, but were also abundant in the gray matter. In contrast, lesions in MOG-EAE were restricted to the lateral and ventral columns and displayed less axonal damage and little gray matter involvement. The differential lesion location was confirmed by quantitation of leukocyte subsets. In both diseases myelin damage was a common feature although the numerous empty myelin sheaths in NF-L-disease indicative of axonal damage suggest that myelin damage was a secondary event.In summary, autoimmunity to NF-L induces a distinct lesion topology, axonal damage and gray matter lesions supporting the notion that axonal loss and gray matter pathology can be the direct consequence of a primary autoimmune attack against axonal antigens such as NF-L rather than merely a secondary event to myelin damage.http://www.sciencedirect.com/science/article/pii/S0969996108001952Multiple sclerosisAnimal modelsLesion distributionNeuroinflammationNeurodegenerationAutoimmunity |
| spellingShingle | Ruth Huizinga Wouter Gerritsen Nicole Heijmans Sandra Amor Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments Neurobiology of Disease Multiple sclerosis Animal models Lesion distribution Neuroinflammation Neurodegeneration Autoimmunity |
| title | Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments |
| title_full | Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments |
| title_fullStr | Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments |
| title_full_unstemmed | Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments |
| title_short | Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments |
| title_sort | axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments |
| topic | Multiple sclerosis Animal models Lesion distribution Neuroinflammation Neurodegeneration Autoimmunity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996108001952 |
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