Mobilization of progenitors in the subventricular zone to undergo oligodendrogenesis in the Theiler's virus model of multiple sclerosis: Implications for remyelination at lesions sites

Remyelination involves the generation of new myelin sheaths around axons, as occurs spontaneously in many multiple sclerosis (MS) lesions and other demyelinating diseases. When considering repairing a diseased brain, the adult mouse subventricular zone (SVZ) is of particular interest since the stem cells in this area can migrate and differentiate into the three major cell types in the central nervous system (CNS). In Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), we assessed the relative contribution of the SVZ to the remyelination in the corpus callosum at preclinical stages in this MS model. CNPase, MBP and Luxol Fast Blue staining revealed prominent demyelination 35 days post-infection (dpi), concomitant with a strong staining in GFAP+ type B astrocytes in the SVZ and the increased proliferation in this area. The migration of oligodendrocyte progenitors from the SVZ contributed to the remyelination observed at 60 dpi, evident through the number of APC+/BrdU+ mature oligodendrocytes in the corpus callosum of infected animals. These data suggest that the inflammation induced by the Theiler's virus not only provokes strong preclinical demyelination but also, it is correlated with oligodendrocyte generation in the adult SVZ, cells that along with resident progenitor cells contribute to the prompt remyelination observed in the corpus callosum.We are grateful to the financial support of the Ministry of Economy and Competitivity (MINECO, project SAF-2010/17501), the Instituto de Salud Carlos III (RETICS programme, Red Española de Esclerosis Múltiple – REEM RD07/0060/0010 and RD12/0032/0008 co-supported by FEDER grants) and the Comunidad de Madrid (CAM - S2010/BMD-2308). Mecha M was supported by REEM.Peer reviewe