The experimental chemical cuprizone destroys myelin via an unexpected mechanism. As reported in a study published online this week in Nature Neuroscience, cuprizone induces neutrophils ― a specific population of white blood cell ― to enter the central nervous system and kill oligodendrocytes (OLs), the myelin-forming cells. These blood cells could be targets for the development of new multiple sclerosis drugs.
Multiple sclerosis (MS) is primarily an autoimmune attack on myelin, the crucial insulation of nerve tracts. The most severe damage in MS, however, is thought to be caused by a combination of autoimmune and toxic mechanisms. In mice, the chemical cuprizone causes this type of severe myelin damage. Richard Ransohoff and colleagues report that cuprizone does not kill OLs in mice that lack CXCR2, the receptor for an inflammation-promoting peptide. With a series of bone marrow transplantation experiments between normal and CXCR2-deficient mice, the researchers determined that CXCR2 had to be present on blood cells, not brain cells, for cuprizone to be toxic to OLs. Removing neutrophils, the only CXCR2-expressing blood cells, from the circulation of normal mice rendered them resistant to the toxic effects of cuprizone.
Cuprizone itself has not been linked to human MS, but other environmental toxins might trigger similar cellular mechanisms. If so, therapeutic approaches targeting neutrophils should be investigated.