Focal white matter lesions induce long-lasting axonal degeneration, neuroinflammation and behavioral deficits

Neurobiology of Disease

Markus Kipp¹  Sebastian Rühling¹  Peter Ponsaerts¹  Bernd Denecke¹  Florian Nepomuk Fegg¹  Julia Frenz²  Tanja Hochstrasser²  Hannes Kaddatz²  Jiangshan Zhan²  Sandra Amor² 

[1] Department of Anatomy II, Ludwig-Maximilians-University of Munich, Munich, Germany;Institute of Anatomy, Rostock University Medical Center, Rostock, Germany;

关键词: Multiple sclerosis;    Gliosis;    Axonal damage;    Remyelination;    Protein kinase c delta;   

DOI  :  

来源: DOAJ

【 摘 要 】

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with episodes of inflammatory demyelination and remyelination. While remyelination has been linked with functional recovery in MS patients, there is evidence of ongoing tissue damage despite complete myelin repair. In this study, we investigated the long-term consequences of an acute demyelinating white matter CNS lesion. For this purpose, acute demyelination was induced by 5-week-cuprizone intoxication in male C57BL/6 J mice, and the tissues were examined after a 7-month recovery period. While myelination and oligodendrocyte densities appeared normal, ongoing axonal degeneration and glia cell activation were found in the remyelinated corpus callosum. Neuropathologies were paralleled by subtle gait abnormalities evaluated using DigiGait™ high speed ventral plane videography. Gene array analyses revealed increased expression levels of various inflammation related genes, among protein kinase c delta (PRKCD). Immunofluorescence stains revealed predominant microglia/macrophages PRKCD expression in both, cuprizone tissues and post-mortem MS lesions. These results support the hypothesis that chronic microglia/macrophages driven tissue injury represents a key aspect of progressive neurodegeneration and functional decline in MS.

【 授权许可】

Unknown