In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice

The mechanisms by which CNS tissue reacts to a demyelinating virus and reconstructs myelinated and functionally ensheathed axons after a dramatic tissue destruction are completely unknown. It is likely that polypeptide factors can trigger mitosis, migration, and differentiation in vivo during remyelination just as they do in vitro. Interleukin 2 has been shown to induce proliferation and differentiation of oligodendroglial cells (Benveniste and Merrill, 1986) Whatever the polypeptide factors involved may be, the end result of the glial cell reaction to mouse hepatitis virus infection is the birth of new oligodendrocytes (see also Herndon, 1977) and efficient remyelination. We cannot exclude that some oligodendrocytes might be able to dedifferentiate, and turn off the expression of myelin protein genes but the presence of a small number of O-2A progenitors in the normal mice suggests that this pool of precursors might be amplified in the course of this demyelinating disease. CNP + oligodendrocytes persisted throughout the course of the infection in many areas not demyelinated, but we rarely saw them labeled after 2 h exposure to tritiated thymidine. Thus, in contrast to previous observations in other models in rat (Aranella and Herndon, 1984; Ludwin and Bakker, 1988), we found no evidence for proliferation of differentiated oligodendrocytes as a substantial component of response to injury. Instead, our results indicate that newly formed oligodendrocytes arise from mitotic 04 + CNP-GFAP-precursors. In vitro analysis of these cells may lead to a more detailed understanding of their behavior and the identification of signal factors which control gliogenesis during remyelination.