The Regulation and Mechanism of Myelin Synthesis Involving Endogenous Steroid Hormones

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Chan, Jonah R.

Contributors dc:contributor

• Glaser, Michael

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI9971042

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82541