The expression of myelin protein mRNAs during remyelination of lysolecithin-induced demyelination

To gain insights into the mechanisms of myelin repair in the CNS and to est ablish the extent to which this process resembles myelination in developmen t we have examined the patterns of expression of transcripts of the major m yelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP) du ring remyelination of lysolecithin-induced demyelination in the adult rat s pinal cord. Injection of 1 mu l 1% lysolecithin into the dorsal funiculus c aused a dramatic decrease in levels of MBP exon 1 and MBP exon 2-containing transcripts and PLP/DM20 transcripts. Between 10 and 21 days post-lesion i nduction there was a gradual increase in levels of expression of all transc ripts, which had returned to levels associated with normally myelinated spi nal cord white matter at 21 days. These increases in levels of expression c orresponded to the appearance of remyelinated axons, detected on toluidine blue-stained resin sections. Foci of high levels of expression occurred in regions of the lesion in which new myelin sheath formation was occurring, a lthough the level of expression throughout the lesion never exceeded levels associated with myelin sheath maintenance in normal white matter due to th e asynchronous pattern of remyelination, The changes in levels of expressio n of MBP exon 2 closely followed those of MBP exon 1. Our results indicate that (i) myelin protein gene expression associated with myelinogenesis duri ng remyelination follows a similar pattern to that of myelinogenesis during development and that (ii) in rat models of demyelination changes of expres sion of MBP exon 1 and exon 2-containing transcripts are of equal value, an observation relevant to quantifying the effects of putative remyelination- enhancing strategies using the lysolecithin model.