Axonal degeneration is an early pathological feature in autoimmune-mediated demyelination in mice.
Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS), characterised by focal destruction of myelin. Although it is evident that the immune system contributes to tissue destruction in MS, it is still unclear as to whether this immune response is a cause or a consequence of the disease process. In addition, there is debate over the contribution of axonal damage to clinical progression. We have described a murine model of relapsing-remitting MS (RR-MS), the most common form of the disease, following immunisation with the myelin component, myelin oligodendrocyte glycoprotein (MOG). We showed that a single injection of a MOG peptide (MOG(35-55)) in NOD/Lt mice induces a paralytic relapsing disease with extensive plaque-like demyelination. This model also mimics many of the immunological features associated with RR-MS. To investigate the relationship between clinical episodes, inflammation, and demyelination/remyelination, we analysed lesions during each attack and remission over the course of the disease, using histological, immunocytochemical, and electron microscopy (EM) techniques. We show that morphological features of lesions in our model resemble those observed in MS. Indeed, severe inflammation and demyelination coincide with the peak of clinical episodes while remissions are characterised by quiescent plaques. Furthermore, axonal damage is evident from the earliest stage of the disease and increases in severity with subsequent relapses. These data establish that in the model of MS-like disease, the peak of clinical episodes coincides with severe inflammation and demyelination and that axonal pathology correlates with clinical progression.
Onuki
M
M
Neuroimmunology Laboratory, Department of Biochemistry, Faculty of Science and Technology, La Trobe University, Bundoora 3083, Victoria, Australia.
Ayers
M M
MM
Bernard
C C
CC
Orian
J M
JM
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D008854:Microscopy, Electron; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000503:physiopathology*