The regulatory mechanisms by which Schwann cells control the expression oif myelin specific glycoconjugates will be evaluated in the presence and absence of myelin assembly and during various levels of Schwann cell differentiation in the following rat sciatic nerve models: neonatal, neonatal after tissue culture, normal adult, crushed adult, and transected adult.
The specific aims of this research plan include 1) control of PO gene expression: to correlate PO mRNA biosynthesis and steady state levels with the in vitro cell-free translation and in vivo biosynthesis of PO to determine if the control is at the transcription, translation, and/or post-translation levels in these models; 2) molecular sorting and intracellular targeting of PO: to quantitate PO biosynthesis in the transected nerve in the presence of lysosomotropic agents, to determine the route of PO targeting to the lysosome by Schwann cells in the transected nerve, and to ascertain the sorting signal on PO responsible for the lysosomal delivery; 3) induction of PO translation in neonatal Schwann cells after co-culture: to evaluate the mechanisms associated with the translational control of PO mRNA in cultured neonatal Schwann cells; and 4) alterations in glycolipid biosynthesis by Schwann cells: to further examine the mechanisms of control associated with the biosynthetic shift from the galactocerebrosides and monogalactosyl diacylglycerol during myelin assembly and maintenance to the glucocerebrosides and oligohexosylceramides in the absence of myelin assembly. It is anticipated that this approach will improve our understanding of the molecular michanisms associated with the initiation of the myelinating process. In addition, information concerning the regulatory events associated with myelination should prove useful for understanding human disease involving, for example, the inflammatory demyelinating peripheral neuropathies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS020551-04
Application #
3400941
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-04-01
Project End
1990-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Poduslo, J F; Walikonis, R S; Domec, M C et al. (1995) The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system. J Neurochem 65:149-59
LeBlanc, A C; Pringle, J; Lemieux, J et al. (1992) Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies. Brain Res Mol Brain Res 15:40-6
LeBlanc, A C; Windebank, A J; Poduslo, J F (1992) P0 gene expression in Schwann cells is modulated by an increase of cAMP which is dependent on the presence of axons. Brain Res Mol Brain Res 12:31-8
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
Gupta, S K; Poduslo, J F; Dunn, R et al. (1990) Myelin-associated glycoprotein gene expression in the presence and absence of Schwann cell-axonal contact. Dev Neurosci 12:22-33
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
Kohriyama, T; Yu, R K; Berg, C T et al. (1990) Sulfate incorporation into peripheral nerve endoneurial glycolipids after crush and permanent transection injury. J Neurosci Res 26:144-8
LeBlanc, A C; Poduslo, J F (1990) Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve. J Neurosci Res 25:162-71
LeBlanc, A C; Poduslo, J F (1990) Axonal modulation of myelin gene expression in the peripheral nerve. J Neurosci Res 26:317-26
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

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