Myelin-Associated Glycoprotein Gene Expression in the Presence and Absence of Schwann Cell-Axonal Contact

Abstract

The distal segments of the crush-injured and permanently transected sciatic nerve provide models to study Schwann cell activity in the presence and absence of Schwann cell-axonal contact, respectively. We examined the quantity and quality of transcript coding for the myelin-associated glycoprotein (MAG) over a 3-week period following crush injury and at 35 days after transection to investigate possible regulation of this gene during nerve injury and subsequent repair. Northern blot and slot blot analysis indicated a sharp decrease in levels of MAG mRNA 2 days after crush injury which was followed by a progressive increase in levels of message between 7 and 21 days after injury. Western blot analysis showed that levels of MAG protein decreased substantially 7 days after crush injury, which returned to 70% of the adult value by 21 days after injury. MAG mRNA and protein were undetectable by Northern and Western analysis, respectively, in the distal segment of the sciatic nerve 35 days after permanent transection. This infers distinct down-regulation of MAG gene expression after permanent transection of a peripheral nerve. These comparative studies of MAG transcripts and encoded protein may indicate regulation of MAG gene expression at the level of transcription, and possibly at the level of post-transcription in these experimental models of peripheral neuropathies.

Axonal modulation of myelin gene expression in the peripheral nerve

“…Analysis of the endoneurial proteins in the distal segments of the nerves revealed differences in the temporal re-expression of the myelin specific proteins (present data and Gupta et al, 1988Gupta et al, , 1990 Schwann cell (Weinberg and Spencer, 1976;Aguayo el al., 1976;Bunge and Bunge, 1978). It is currently believed that the axon providcs a crucial signal to the Schwann cell in order to initiate both myelin specific gene expression and myelin assembly in the peripheral nerve (Mirsky et a]., 1980: Politis et al, 1982.…”

“…However, the return of myelin specific mRNA to normal levels as early a5 14 days after injury, when axonal regeneration has not yet been completed, suggests higher levels of P,, and MBP mRNAs in regions where there is direct axonal-Schwann cell contact compared to a presumably uniform distribution in normal nerve. In the distal segment of the crushed nerve, MAG mRNA decrcascd to low levcls by 2 days of injury and increased slowly but constantly thereafter (Gupta et al, 1990). These results indicate that P,, and MBP mRNA are constitutively expressed by the Schwann cell in the absence of direct axonal contact.…”

Primary demyelination induced by exposure to tellurium alters Schwann cell gene expression: a model for intracellular targeting of NGF receptor

“…In vivo, a viable axon is necessary not only to initiate the commitment of Schwann cells to myelination, but also to maintain the differentiated Schwann cell. Transection of a peripheral nerve is followed by rapid and profound downregulation of the myelin protein genes (LeBlanc et al, 1987;Gupta et al, 1988Gupta et al, , 1990Trapp et al, 1988;LeBlanc and Poduslo, 1990;Thompson et al, 1991) and loss of galactocerebroside (Jessen et al, 1987b). There is a concomitant reexpression of NGF-R (Taniuchi et al, 1986(Taniuchi et al, , 1988Heumann et al, 1987;Bosch et al, 1989) and N-CAM (Nieke and Schachner, 1985;Daniloffetal., 1986;Jessenetal., 1987a) in thedenervated Schwann cells.…”

“…There is a concomitant reexpression of NGF-R (Taniuchi et al, 1986(Taniuchi et al, , 1988Heumann et al, 1987;Bosch et al, 1989) and N-CAM (Nieke and Schachner, 1985;Daniloffetal., 1986;Jessenetal., 1987a) in thedenervated Schwann cells. The processes involved in myelination during development are recapitulated during the regeneration that occurs subsequent to a nerve crush (Gupta et al, 1988(Gupta et al, , 1990LeBlanc and Poduslo, 1990;Mitchell et al, 1990).…”

Expression of β‐1,4‐galactosyltransferase I in rat Schwann cells

“…As we know, Schwann cells de-differentiate and proliferate after axotomy of peripheral nerves [Bunge, 1993]. The denervated Schwann cells are known to upregulate expression of a number of cell surface molecules which are presumed to aid axonal regeneration, including NCAM, L1, CHL1, and p75 [Gupta et al, 1990;LeBlanc and Poduslo, 1990]. b-1,4-GalT I has been found on the plasma membrane of different types of cells where it serves as a cell surface adhesion molecule, mediating various cell-cell and cell-matrix interactions such as sperm-egg binding, cell spreading, migration, and neurite outgrowth [Huang et al, 1995;Lu and Shur, 1997;Shi et al, 2001].…”