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Cell-cell interactions limiting functional repair after spinal cord injuries.

One of the major impediments to successful recovery of function after a spinal cord injury is the reaction of the neuronal growth cone to inhibitory influences in the local environment in or around the site of injury. In tissue culture, contact with oligodendrocytes inhibits neuronal growth cones. However, this inhibition of growth cone motility is dependent on the level of maturity of the oligodendrocyte. Oligodendrocytes go through five stages in their maturation from precursors (Stage 1) to mature myelinating oligodendrocytes (Stage 5) both in vivo and in vitro. At each of the five stages in their differentiation, oligodendrocytes express an additional complement of surface molecules. Only contact with the intermediate three stages (2 - 4) causes inhibition of growth cone motility in tissue culture. The inhibition of growth cone motility that results from contact with Stage 3 and 4 oligodendrocytes can be blocked by pertussis toxin. However, the inhibition induced by contact with a Stage 2 oligodendrocyte cannot. This suggests that there are multiple mechanisms that lead to contact-induced inhibition of growth cone motility. Extending his earlier APA-supported research, Dr. Moorman proposes to determine the cellular mechanisms that underlie growth cone contact with oligodendrocytes at each of the five stages of differentiation. This is a particularly appealing approach because it defines the cellular mechanisms that underlie growth cone inhibition that results from the growth coneÕs integration of many signals. In addition, he will explore ways to block those mechanisms. Knowing the cellular mechanisms that underlie the interactions of neurons and oligodendrocytes provides a rational basis for developing therapies to enhance regeneration and functional repair of the injured spinal cord.

Funded by the American Paralysis Association and by Prevent Blindness America/Fight For Sight

Abstracts:

Moorman, S.J., L.R. Whalen, and H.O. Nornes (1987): Studies of hindlimb reflexes in the adult rat: A non-invasive test of the central excitatory state of the spinal cord. Abstract in Proceedings of Society for Neurosciences, vol 13.

Moorman, S.J., L.R. Whalen, and H.O. Nornes (1988): Hindlimb reflexes affected by fetal brainstem tissue implanted in the spinal cord of the rat. Abstract in Proceedings of Society for Neurosciences, vol. 14.

Moorman, S.J. and R.I. Hume (1989): Time-lapse observation of neurite growth by sympathetic preganglionic neurons in vitro. Abstract in Proceedings of Society for Neurosciences, vol. 15.

Moorman, S.J. and R.I. Hume (1990): Cell-specific Growth cone behaviors suggestive of pathway and target recognition. Development and Plasticity of the Spinal Cord Conference, Ohio State University.

Moorman, S.J. and R.I. Hume (1991): Three cell-specific growth cone behaviors suggestive of pathway and target recognition in vitro. Proceedings of I.B.R.O. Satellite Symposium on Spinal cord development, plasticity and regeneration.

Moorman, S.J. and R.I. Hume (1991): An increase in internal free calcium concentration coincides with two different growth cone behaviors. Abstract in Proceedings of Society for Neurosciences, vol 17.

Moorman, S.J., and R.I. Hume (1992): Contact with myelin causes a release of calcium from internal stores in oligodendrocytes. Abstract in Proceedings of Society for Neurosciences, vol 18.

Gould, R.M. and S.J. Moorman (1995): Culturing neural cells from dogfish embryos. Journal of Neurochemistry, vol 65 supplement 1

Moorman, S.J. (1995): Pertussis toxin blocks the effects of contact between oligodendrocytes in vitro. Abstract in Proceedings of Society for Neurosciences, vol 21.

Stokely, M.E. and S.J. Moorman (1996) Retina trophically supports oligodendrocytes from the optic nerve in vitro. Abstract in Proceedings of Society for Neurosciences, vol 22.

Moorman, S.J. and R.M. Gould (1996) Maturing oligodendrocytes inhibit neuronal growth cone motility in different ways. Abstract in Proceedings of Society for Neurosciences, vol 22.

Book Chapters:

Moorman, S.J. and L.R. Whalen (1991): Fetal implants in the lesioned spinal cord of the rat. Methods in Neurosciences 7:300-304

Nornes, H.O., S.J. Moorman, A.R. Mihajlov, B.E. Pulford and L.R. Whalen (1992): Intraspinal transplants of catecholamine containing cells and fetal spinal cord and iris tissues in the adult rat. Advances in Neurology 59:185-197

Moorman, S.J. (1996): Does myelin limit regeneration and remyelination? in: Molecular Signaling and Regulation in Glial Cells: A Key to Remyelination and Functional Repair, G. Jeserich, H.H. Althaus, C. Richter-Landsberg, R. Heumann eds. Springer Verlag, Heidelberg. pp.243-254

Articles :

Moorman, S.J., L.R. Whalen, and H.O. Nornes (1990): A neurotransmitter specific functional recovery mediated by fetal implants in the lesioned spinal cord of the rat. Brain Res. 508:194-198

Moorman, S.J. and R.I. Hume (1990): Growth cones of chick sympathetic preganglionic neurons in vitro interact with other neurons in a cell-specific manner. J. Neurosci. 10:3158-3163

Moorman, S.J., and L.R. Whalen (1993): A model system to determine the effects of specific neurotransmitters on segmental reflexes in the spinal cord of the rat. J. Neurosci. Meth. 46:73-81

Moorman, S.J., and R.I. Hume (1993): Omega-conotoxin prevents myelin-evoked growth cone collapse in neonatal-rat brainstem neurons in-vitro. J. Neurosci. 13:4727-4736

Moorman, S.J. and R.I. Hume (1994): Contact with myelin in-vitro evokes a release of calcium from internal stores in neonatal rat oligodendrocytes. GLIA 10:202-210

Moorman, S.J. and R.I. Hume (1994): Locus Coeruleus Growth Cones and Spinal Cord Regeneration. Brain Research Bulletin 35:419-422

Gould, R.M., A.M. Fannon, and S.J. Moorman (1995): Neural cells from dogfish embryos express the same subtype-specific antigens as mammalian neural cells in vivo and in vitro. GLIA 15:401-418

Moorman, S.J. (1996): The inhibition of motility that results from contact between oligodendrocytes in vitro can be blocked by pertussis toxin. GLIA 16:257-265

Moorman, S.J. and R.M. Gould (1997): Differentiating oligodendrocytes inhibit neuronal growth cone motility in different ways. In press, J. Neurosci. Res.
  

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