Expression of myelin protein gene transcripts by schwann cells of regenerating nerve

Mitchell, L. S.; Griffiths, I. R.; Morrison, Steven; Barrie, Jennifer A.; Kirkham, D.; McPhilemy, K.

doi:10.1002/jnr.490270202

Cited by 59 publications

(41 citation statements)

References 36 publications

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“…In control nerves, P, mRNA showed a strong focal perinuclear signal located in the mid-internode (Fig. 3A, inset), as previously reported (Griffiths et al, 1989;Mitchell et al, 1990). Signal intensity is related to fiber size (larger internodes are more intensely labeled) and is of approximately equal intensity in contiguous internodes along the same fiber (Griffiths et al, 1991).…”

Section: Resultssupporting

confidence: 84%

“…Antisense and sense RNA probes labeled with 35S-UTP were transcribed. Full details of the P,, probe have been published previously (Griffiths et al, 1989;Mitchell et al, 1990). The probe for the rat NGF-R was a 1.7 kilobase EcoRI/BglII fragment of the pNGFR.1 plasmid (Raedeke et al, 1987), subcloned into pBluescript II KS (+; Stratagene).…”

Section: Methodsmentioning

confidence: 99%

“…The probe for the rat NGF-R was a 1.7 kilobase EcoRI/BglII fragment of the pNGFR.1 plasmid (Raedeke et al, 1987), subcloned into pBluescript II KS (+; Stratagene). Hybridizations were performed on frozen sections and on bundles of teased fibers essentially as described previously (Griffiths et al, 1989;Mitchell et al, 1990). Autoradiograms of teased fibers were stained with Sudan black B to visualize myelin.…”

Section: Methodsmentioning

confidence: 99%

“…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).…”

Section: Primary Demyelination Induced By Exposure To Tellurium Altermentioning

confidence: 99%

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

et al. 1992

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Exposure of developing rats to tellurium results in a highly synchronous segmental demyelination of peripheral nerves with sparing of axons; this demyelination is followed closely by a period of rapid remyelination. Demyelination occurs subsequent to a tellurium-induced block in the synthesis of cholesterol, the major myelin lipid. We utilized the techniques of Northern blotting, in situ hybridization, and immunocytochemistry to examine temporal alterations in Schwann cell gene expression related to demyelination and remyelination. Tellurium- induced demyelination is associated with downregulation of myelin protein expression and a corresponding upregulation of NGF receptor (NGF-R) and glial fibrillary acidic protein (GFAP) expression. Steady- state mRNA levels (expressed on a “per nerve” basis) for P0, the major myelin protein, were decreased by about 50% after 5 d of tellurium exposure, while levels of mRNA for NGF-R and GFAP were markedly increased (about 15-fold). In situ hybridization of teased fibers suggested that the increase in steady-state mRNA levels for NGF-R was primarily associated with demyelinated internodes and not with adjacent unaffected internodes. Although P0 message was almost totally absent from demyelinating internodes, it was also reduced in normal-appearing internodes as well. This suggests that limiting the supply of a required membrane component (cholesterol) may lead to partial downregulation of myelin gene expression in all myelinating Schwann cells. In partially demyelinated internodes, NGF-R and GFAP immunofluorescence appeared largely confined to the demyelinated regions. This suggests specific targeting of these proteins to local areas of the Schwann cell where there is myelin loss. These results demonstrate that demyelination is associated with reversion of the affected Schwann cells to a precursor cell phenotype. Because axons remain intact, our results suggest that these changes in Schwann cell gene expression do not require input from a degenerating axon, but instead may depend on whether concerted synthesis of myelin is occurring.

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Section: Resultssupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Primary Demyelination Induced By Exposure To Tellurium Altermentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 1992

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“…Although the molecular mechanisms have yet to be elucidated, it seems that both the basal lamina and the Schwann cells that persist in the distal stump have a role in promoting axonal regeneration in the PNS (Bunge et al, 1989;Hagg et al, 1991;Bunge, 1993;Ide, 1996). Once premyelinating Schwann cells have re-established physical contact with axons, the changes in Schwann cell gene expression caused by Wallerian degeneration are reversed: the levels of myelinrelated mRNAs increase and NGFR and GAP-43 decrease (Mitchell et al, 1990;Gupta et al, 1993;Scherer and Salzer, 1996).…”

Section: Introductionmentioning

confidence: 93%

Transient expression of the neurofilament proteins NF-L and NF-M by Schwann cells is regulated by axonal contact

et al. 1997

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Expression of the genes that encode neurofilament proteins is considered to be confined normally to neurons. However, in demyelinating peripheral nerves Schwann cells upregulate the mRNA for the medium-sized neurofilament protein (NF-M), and cultured Schwann cells of the myelin-forming phenotype can also synthesize and incorporate NF-M protein into their intermediate filament (IF) cytoskeleton. The purpose of this study was to establish how axonal contact might influence glial neurofilament gene expression and regulate the synthesis of neurofilament proteins. We show that the gene encoding NF-M is expressed at early stages of differentiation in myelin-forming Schwann cells in vivo; nevertheless, little NF-M protein can be detected in these cells. The transient induction of NF-M mRNA is also apparent in dedifferentiating Schwann cells during Wallerian degeneration. In these Schwann cells the mRNAs for NF-M and NF-L (the smallest polypeptide), but not NF-H (the largest neurofilament subunit), are coordinately expressed. In contrast to differentiating myelin-forming Schwann cells, the cells of degenerating nerves express both NF-M and NF-L polypeptides. Restoration of axonal contact in the growing nerve stimulates the recapitulation of Schwann cell differentiation including the elevation of NF-M and NF-L mRNA expression. These results demonstrate that the transient induction of neurofilament mRNAs in Schwann cells is a feature of both differentiation and dedifferentiation. However translation of these mRNAs is confined to Schwann cells deprived of axonal contact either by nerve injury or by culture in the absence of axons. These findings suggest that the expression of the NF-M and NF-L polypeptides is an important characteristic of those Schwann cells that will contribute to the repair of damaged peripheral nerves.

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Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve

1998

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Following injury to the peripheral nervous system, circulating monocytes/macrophages are recruited to the damaged tissue, where they play vital roles during both nerve degeneration and subsequent regeneration. Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C or beta-chemokine family, is a powerful leukocyte recruitment/activation factor that is relatively specific for monocytes/macrophages. Because these are the predominant leukocyte type recruited by injured nerve, we hypothesized that upregulation of MCP-1 expression is involved in recruitment of these cells. Indeed, assay of steady-state levels of MCP-1 mRNA in rat sciatic nerve during tellurium-induced primary demyelination indicated up-regulation of this chemokine with a peak after 3 days of tellurium exposure, preceding the peak of accumulation of phagocytic macrophages (assayed as lysozyme mRNA levels) by 6 days. Increasing levels of MCP-1 mRNA expression, induced by increasing levels of tellurium exposure, resulted in corresponding increases in subsequent recruitment of macrophages. In situ hybridization suggested that MCP-1 mRNA was localized in Schwann cells. No expression of MIP-2, which is a C-X-C or alpha-chemokine that is specific for recruitment of neutrophils, was detected, consistent with the lack of recruitment of significant numbers of these cells. In addition, we also investigated the response seen following nerve transection (axonal degeneration and secondary demyelination with no subsequent regeneration) and nerve crush (degeneration followed by regeneration). In these latter two nerve injury models, there was also a marked, early up-regulation of MCP-1 mRNA, with a time course that is compatible with a role for this chemokine in macrophage recruitment. We conclude that MCP-1 is involved in recruiting monocytes/macrophages to injured peripheral nerve and that the specificity of leukocyte types recruited results from specificity of chemokine production.

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Expression of myelin protein gene transcripts by schwann cells of regenerating nerve

Cited by 59 publications

References 36 publications

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

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

Transient expression of the neurofilament proteins NF-L and NF-M by Schwann cells is regulated by axonal contact

Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve

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