CNS Myelination and Glial Cell Transplantation
Office Phone: (608) 263-9828, (608) 263-8399
Myelination of the mammalian CNS is a complex developmental process that requires intricate timing of gene expression and cellular interactions between the axon and its myelinating cell, the oligodendrocyte. A deeper understanding of normal myelination has been provided by the study of the myelin mutants, animals in which these developmental processes have been interrupted, as a result of mutations in myelin genes. We have been studying these mutants using morphological, tissue culture, and molecular approaches. Some of these mutants serve as bona fide models of human disease, and allow us opportunities to study repair as a translational step toward human therapies. In particular, we are exploring the role that transplantation of glial cells might play in repairing focal lesions in multiple sclerosis and more generalized defects in the people with genetic disorders. To accomplish this, we are defining the type of cell that could be transplanted, beginning from embryonic stem cells and their derivatives through tissue-specific progenitors. We are also developing new models to study such repair, and are exploring the mechanisms of compounds or molecules that may help promote repair, lessen inflammation, and protect transplanted cells. Finally, with collaborators, we are developing new imaging techniques to study cell migration of transplanted cells in vivo and the myelin that they make.
- Nikodemova, M., J.J. Watters, S. Jackson, S. Yang, I.D. Duncan. 2007. Minocycline down-regulates MHC II expression in microglia through inhibition of IRF-1 and PKCαβ? J. Biol. Chem. 282: 15208-15216.
- Nikodemova, M, I.D. Duncan, J.J. Watters. 2006. Minocycline attenuates inhibitory effects on multiple mitogen-activated protein kinases and IκBα degradation in a stimulus-specific manner in microglia. J. Neurochem. 96: 314-323.
- Li, F-Y, P.A. Cuddon, J. Song, S.L. Wood, J.S. Patterson, G.D. Shelton, I.D. Duncan. 2006. Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b. Neurobiol. Dis. 21: 35-42.
- Kondo, Y., D.A. Wenger, and I.D. Duncan. 2005. Galactocerebrosidase-deficient oligodendrocytes maintain stable central myelin by exogenous replacement of the missing enzyme in mice. Proc. Nat. Acad. Sci.102: 18670-18675.
- Edgar, J.M., M. McLaughlin, D. Yool, S.C. Zhang, J. Fowler, P. Montague, J.A. Barrie, M.C. McCulloch, I.D. Duncan, J. Garbern, K.A. Nave, I.R. Griffiths. 2004. Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia. J. Cell. Biol. 166: 121-131.
- Song, J., J. H. Carson, E. Barbarese, F. Li and I. D. Duncan. 2003. RNA transport in oligodendrocytes from the taiep mutant rat. Mol. Cell. Neurosci. 24: 926-938.
- Popovic, N., B.D. Goetz, A. Schubart, C.R. Linington, and I.D. Duncan. 2002. Inhibition of autoimmune encephalitis by a tetracycline. Anns. Neurology 51: 215-223.
- Zhang, S.C., M. Wernig, I.D. Duncan, In vitro differentiation and transplantation of human ES cell-derived neural precursors. O. Brustle, and J.A. Thomson. 2001. Nat. Biotech. 19: 1129-1133.
- Brustle, O., K.N. Jones, R.D. Learish, K. Karram, K. Choudhary, O.D. Wiestler, I.D. Duncan, and R.D.G. McKay. 1999. Embryonic stem cell-derived glial precursors: A source of myelinating transplants. Science 285: 754-756.