MORPHOLOGY OF OLIGODENDROCYTES DURING DEMYELINATION IN OPTIC NERVES OF MICE INFECTED WITH SEMLIKI-FOREST-VIRUS

Multiple sclerosis (MS) is a demyelinating disease which affects oligo dendrocytes, the myelinating cells of the CNS. Demyelination is known to occur in the optic nerves of Balb/c mice infected with the avirulen t A7(74) strain of Semliki Forest virus (SFV), and many of the changes are similar to those of patients with MS. The aim of the present stud y was to determine how demyelination proceeds in individual oligodendr ocytes in SFV infection, to help in understanding the pathology of dem yelination and remyelination in MS. The whole-cell morphology of indiv idual oligodendrocyte units (defined as the oligodendrocyte, its proce sses and the internodal myelin segments of the axons it ensheaths) was characterized using intracellular dye injection in isolated intact op tic nerves. In untreated control mice, oligodendrocytes had a relative ly uniform morphology and each cell on average provided 20 or so nearb y axons with single myelin sheaths with internodal lengths of similar or equal to 150 mu m. In SFV infected mice, during the peak of demyeli nation at postinoculation days 14-21, 55% of oligodendrocytes displaye d a range of morphological abnormalities, which most likely represente d sequential changes in oligodendrocytes during demyelination. Thus, a t the earliest stage of demyelination oligodendrocytes developed swell ings or vacuolations along their internodal myelin sheaths, which beca me gradually attenuated and were completely lost in extreme cases. The results show that whole oligodendrocyte units were affected during SF V-induced demyelination and this is the basis of the focal nature of l esions in this viral model of MS. Individual oligodendrocyte units whi ch had lost their full complement of myelin sheaths had the appearance of immature oligodendrocytes, suggesting they had undergone de-differ entiation. We concluded that these cells may not be destroyed during d emyelination and it is possible they are capable of remyelination whic h is a feature of SFV infection in mice and MS in humans.