Contrasting roles for axonal degeneration in an autoimmune versus viral model of multiple sclerosis: When can axonal injury be beneficial?
Although demyelination is a cardinal feature in multiple sclerosis, axonal injury also occurs. We tested whether a delay in axonal degeneration could affect the disease severity in two models for multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus (TMEV) infection. We compared wild-type C57BL/6 (B6) mice with C57BL/Wld(s) (Wld) mice, which carry a mutation that delays axonal degeneration. In EAE, both mouse strains were sensitized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide and showed a similar disease onset, MOG-specific lymphoproliferative responses, and inflammation during the acute stage of EAE. However, during the chronic stage, B6 mice continued to show paralysis with a greater extent of axonal damage, demyelination, and MOG-specific lymphoproliferative responses compared with Wld mice, which showed complete recovery. In TMEV infection, only Wld mice were paralyzed and had increased inflammation, virus antigen-positive cells, and TMEV-specific lymphoproliferative responses versus infected B6 mice. Because TMEV can use axons to disseminate in the brain, axonal degeneration in B6 mice might be a beneficial mechanism that limits the virus spread, whereas slow axonal degeneration in Wld mice could favor virus spread. Therefore, axonal degeneration plays contrasting roles (beneficial versus detrimental) depending on the initiator driving the disease.
Tsunoda
Ikuo
I
Department of Neurology, University of Utah School of Medicine, 30 North 1900 East, Room 3R330, Salt Lake City, UT 84132, USA.
Tanaka
Tomoko
T
Terry
Emily Jane
EJ
Fujinami
Robert S
RS
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009154:Mutation; D063308:Myelin-Oligodendrocyte Glycoprotein; D009410:Nerve Degeneration; D010446:Peptide Fragments / Q000276:immunology; D013045:Species Specificity; D017945:Theilovirus; D013997:Time Factors
D000956:Antigens, Viral; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)