Understanding the processes involved in the regulation of Schwann cell (SC) phenotype will greatly aid in the diagnosis and ultimate treatment of certain dysmyelinating peripheral neuropathies. It is well documented that neuronal axons influence many aspects of SC behavior, including the ability of SCs to achieve a mature, myelinating phenotype. It now appears that axonal contact can initiate the biosynthesis of the major myelin glycoprotein, PO, in the absence of active myelination, suggesting that the processes of myelin protein synthesis and myelin assembly are distinct events regulated independently. The studies presented in this proposal are aimed at obtaining an understanding of the mechanism whereby axons trigger SCs to synthesize myelin proteins in the absence or presence of active myelination. It is difficult to assay for the induction of myelin protein expression with SCs derived from myelinating nerve, as such cells continue to express PO (and perhaps other myelin proteins) in the absence of axonal influence. To alleviate this problem, SCs from the cervical sympathetic trunk (CST SCs) have been partially characterized and shown not to synthesize appreciable levels of PO either in vivo or after growth in culture. These cells will be characterized further and used to address the regulation of myelin protein synthesis. Experiments are proposed that will: 1) determine and compare the level of expression of the myelin proteins PO, MAG, and MBPs in non- myelinating and myelinating dorsal root ganglia (DRG)/endogenous SC cultures. This will reveal whether axons are sufficient to induce synthesis of other myelin proteins besides PO, as well as indicate the degree of upregulation of such proteins during active myelination; 2) quantitate the levels of PO, MAG, and MBPs biosynthesis in adult CST SCs to ascertain whether the expression of the latter two myelin proteins are suppressed to the same extent as PO; 3) determine the levels of synthesis of the myelin proteins by CST SCs after they have been seeded onto, DRG neurites in media that are capable and incapable of supporting myelination; 4) examine the DRG neurite cultures for the nature of the signal(s) triggering expression of myelin proteins. The CST SCs will be employed to aid in the assaying of such a component(s); 5) begin initial biochemical characterization and isolation of any myelin protein induction molecule(s) identified. The studies described should greatly increase the body of knowledge dealing with the expression of myelin proteins, and the culture systems employed will be useful in future studies addressing SC phenotypic changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29NS027587-01
Application #
3477805
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Mississippi Medical Center
Department
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Beaman-Hall, C M; Wainer, B H; Eves, E et al. (1996) Expression of glucocorticoid and mineralocorticoid receptors in an immortalized hippocampal neuronal cell line. Brain Res 726:141-52
Brunden, K R; Gregory, R; Yoshino, J E et al. (1994) Role of basal lamina in Schwann cell glycolipid biosynthesis. Neurochem Res 19:1277-81
Ding, Y; Brunden, K R (1994) The cytoplasmic domain of myelin glycoprotein P0 interacts with negatively charged phospholipid bilayers. J Biol Chem 269:10764-70
Brunden, K R (1992) Age-dependent changes in the oligosaccharide structure of the major myelin glycoprotein, P0. J Neurochem 58:1659-66
Brunden, K R; Ding, Y; Hennington, B S (1992) Myelin protein expression in dissociated superior cervical ganglia and dorsal root ganglia cultures. J Neurosci Res 32:507-15
Brunden, K R; Windebank, A J; Poduslo, J F (1990) Role of axons in the regulation of P0 biosynthesis by Schwann cells. J Neurosci Res 26:135-43
Brunden, K R; Poduslo, J F (1990) Posttranslational degradation of the major myelin glycoprotein by Schwann cells in vivo and in vitro. Ann N Y Acad Sci 605:230-9
Brunden, K R; Windebank, A J; Poduslo, J F (1990) Catabolic regulation of the expression of the major myelin glycoprotein by Schwann cells in culture. J Neurochem 54:459-66
Brunden, K R; Brown, D T (1990) P0 mRNA expression in cultures of Schwann cells and neurons that lack basal lamina and myelin. J Neurosci Res 27:159-68