Differential exon expression in myelin basic protein transcripts during central nervous system (CNS) remyelination

Abstract

1. In order to characterize some of the molecular events leading to repair of myelin in the adult central nervous system (CNS), we examined the expression of transcripts for myelin basic protein (MBP) during remyelination in the mouse. C57B1/6 mice develop a demyelinating disease when glial cells are selectively infected by the A59 strain of mouse coronavirus. The virus is spontaneously cleared from the mice by 4 weeks postinfection (WPI), a time when remyelination is starting. 2. At 3 WPI total MBP transcripts are decreased by 75% in demyelinating lesions compared to control white matter. Using RNase protection assays and in situ hybridization with probes for particular MBP exons, we detected an increase in MBP transcripts containing exon 2 information, coincident with the earliest histological signs of remyelination. 3. The expression of MBP transcripts containing exon 2 information was first seen clustered in the perinuclear cytoplasm of oligodendrocytes scattered within the lesions. This is reminiscent of the increased levels and perinuclear clustering of MBP transcripts containing exon 2 seen during early developmental myelination. The peak abundance of exon 2-containing transcripts in the lesions was 13-fold that seen in control white matter. At later stages of remyelination, additional forms of MBP transcripts (without exon 2) increased and their distribution was more diffuse. 4. Thus, during remyelination, preforms of MBP transcripts, which are normally present at low levels in the adult CNS, are abundantly expressed and regulated in a manner similar to that observed in developmental myelination.

Regulation of Myelin Oligodendrocyte Glycoprotein in Different Species throughout Development

“…The expression of MBP and PLP also displayed a caudo-rostral gradient in agreement with many previous reports at both the protein and mRNA level [5,27,28,32,33], Sig nificantly, in both the spinal cord and brain, the 28 kD band of MOG appeared before the other MOG-reactive bands. If there are indeed isoforms of MOG, it could be that these different isoforms play important roles at dif ferent stages in myelin biogenesis.…”

“…If there are indeed isoforms of MOG, it could be that these different isoforms play important roles at dif ferent stages in myelin biogenesis. This has been shown to be the case for MBP, where exon 2 containing MBP iso forms show peak expression levels early in myelination and decrease thereafter [33]. Alternatively, if the 55 kD band represents a homodimer or heterodimer, then its formation may have a critical role to play in the final stages of myelination.…”

Apotransferrin promotes the differentiation of two oligodendroglial cell lines

“…Some authors (Jordan et al, 1990;Capello et al, 1997) have found that the expression of exon II-containing isoforms peaks during the initial stages of myelination and also at the onset of remyelination in mouse and human studies. The in vitro data presented in this study are consistent with our previous work in myelin isolated from aTf-injected animals (Escobar Cabrera et al, 1994).…”

In vivo proliferation of oligodendrocyte progenitors expressing PDGF?R during early remyelination

“…We have induced transient, focal demyelination followed by efficient remyelination and recovery of function in C57Bl/6 mice by intracranial (i.c.) injection of murine hepatitis virus strain A-59 (MHV-A59) (Lavi et al, 1984;Woyciechowska et al, 1984;Kristensson et al, 1986;Jordan et al, 1989Jordan et al, , 1990Godfraind et al, 1989;Armstrong et al, 1990b). MHV-A59 is a coronavirus that lytically infects glial cells (Dubois-Dalcq et al, 1982), resulting in focal areas of demyelination throughout the brain and spinal cord.…”