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 establish the extent to which this process resembles myelination in development we have examined the patterns of expression of transcripts of the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP) during remyelination of lysolecithin-induced demyelination in the adult rat spinal cord. Injection of 1 microliter 1% lysolecithin into the dorsal funiculus caused 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 induction there was a gradual increase in levels of expression of all transcripts, which had returned to levels associated with normally myelinated spinal cord white matter at 21 days. These increases in levels of expression corresponded 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, although the level of expression throughout the lesion never exceeded levels associated with myelin sheath maintenance in normal white matter due to the asynchronous pattern of remyelination. The changes in levels of expression of MBP exon 2 closely followed those of MBP exon 1. Our results indicate that (i) myelin protein gene expression associated with myelinogenesis during remyelination follows a similar pattern to that of myelinogenesis during development and that (ii) in rat models of demyelination changes of expression 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.
MRC Cambridge Centre for Brain Repair, Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, UK.
R H
RH
Woodruff
R J
RJ
Franklin
D000818:Animals; D001345:Autoradiography; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism*; D005091:Exons; D005260:Female; D017403:In Situ Hybridization; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009185:Myelin Proteins / Q000096:biosynthesis*; D018991:Myelin Proteolipid Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure
D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D015345:Oligonucleotide Probes; D012333:RNA, Messenger