Complement involvement in demyelination and remyelination in the murine cuprizone model

Complement pathways are crucial for host immune protection, however, in some cases complement proteins can contribute to the pathology of autoimmune diseases, such as multiple sclerosis. In our lab we use a demyelination/remyelination model, the cuprizone model, to study different effects of complement proteins. Currently, I am studying C3 and downstream anaphylatoxins, C3a and C5a, and their involvement in demyelination and remyelination. I am also interested in determining signaling pathways utilized by anaphylatoxins through their respective receptors on primary glial cells, in addition to downstream effects of this signaling. Past research projects involved looking at the mRNA expression levels of inflammatory and regulatory complement proteins in primary glial cell cultures and determining the transcriptional regulation of anaphylatoxin receptor genes, C5aR and C3aR, in primary astrocytes.

Ingersoll SA, Martin CB, Barnum SR, Martin BK. CNS-specific expression of C3a and C5a exacerbate demyelination severity in the cuprizone model. Mol Immunol. 2010 Nov-Dec;48(1-3):219-30. Epub 2010 Sep 1. PubMed PMID: 20813409; PubMed Central PMCID: PMC2993815.

Briggs DT, Martin CB, Ingersoll SA, Barnum SR, Martin BK. Astrocyte-specific expression of a soluble form of the murine complement control protein Crry confers demyelination protection in the cuprizone model. Glia. 2007 Nov 1;55(14):1405-15. PubMed PMID: 17674370.

Martin CB, Ingersoll SA, Martin BK. Transcriptional control of the C3a receptor gene in glial cells: Dependence upon AP-1 but not Ets. Mol Immunol. 2007 Feb;44(5):703-12. Epub 2006 Jul 18. PubMed PMID: 16854466.

Martin CB, Ingersoll SA, Martin BK. Regulation of the C5a receptor promoter in glial cells: Minimal dependence upon the CCAAT element in astrocytes. Mol Immunol. 2007 Feb;44(5):713-21. Epub 2006 Jun 5. PubMed PMID: 16750856.