The Regulation and Mechanism of Myelin Synthesis Involving Endogenous Steroid Hormones
Chan, Jonah R.
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https://hdl.handle.net/2142/82541
Description
Title
The Regulation and Mechanism of Myelin Synthesis Involving Endogenous Steroid Hormones
Author(s)
Chan, Jonah R.
Issue Date
2000
Doctoral Committee Chair(s)
Glaser, Michael
Department of Study
Neuroscience
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Biochemistry
Language
eng
Abstract
In conjunction to the previous study, the platelet-derived growth factor (PDGF) A-chain was detected as two distinct splice variants in Schwann cell/neuronal co-cultures. Both PDGF A-chain isoforms were characterized and examined throughout the myelination process. The mRNA for the long form PDGF A-chain was found to be induced during myelin synthesis and was localized to the DRG neurons. Using an antibody generated against the exon 6 peptide, observations suggest that the splice variant is localized to the surface of axons and to certain Schwann cells that are elongated and ensheathing axons. Since the long form PDGF A-chain is thought to be retained on cellular surfaces by the binding of the basic carboxy-terminal to membrane associated heparan sulfate proteoglycans (HSPG), surface competition experiments were performed with heparin and the basic peptide encoded by exon 6. Heparin and the exon 6 peptide were both found to dramatically inhibit the initiation of myelin formation. While these results are still preliminary, they seem to suggest that the splice variant of the PDGF A-chain/HSPG complex functions as a novel neuronal signal that may regulate steroid biosynthesis in Schwann cells and ultimately lead to the initiation of myelin synthesis.
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