Axon Damage Illuminated

Abstract

Biomedicine![Figure][1] Normal-appearing white matter CREDIT: NIKIC ET AL., NAT. MED. 17 , 10.1038/NM.232 (2011) ![Figure][1] Lesion CREDIT: NIKIC ET AL., NAT. MED. 17 , 10.1038/NM.232 (2011) Pathogenesis of the autoimmune disease multiple sclerosis (MS) is associated with progressive deterioration of the myelin sheath surrounding neuronal axons; however, axon damage may also contribute to MS-associated neurodegeneration. Nikic et al. used in vivo imaging and electron microscopy to examine axon damage in a mouse model of MS (EAE, experimental autoimmune encephalitis). In EAE mice, swelling in discrete sites on axons was observed, which was then followed by axon fragmentation. In many cases, damaged axons retained myelin; in some cases, axon damage was reversible. Axon damage was preceded by mitochondrial pathology, which was associated with the presence of microglia and the production of reactive oxygen and nitrogen species. Induction of oxidative or nitrosative stress was sufficient to induce mitochondrial pathology and axon damage in normal mice, and their blockade in EAE mice alleviated axon damage. Lesion biopsies from MS patients also showed similar axon (above, right) and mitochondrial damage, which suggests that reversing axon damage may be an important therapeutic strategy in the treatment of MS. Nat. Med. 17 , 10.1038/nm.2324 (2011). [1]: pending:yes