TROPHIC FACTOR EXPRESSION BY ENSHEATHING GLIA

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Neurotrophic interactions are critical to many developmental processes in the nervous system and are thought to contribute to regenerative events as well. Glial cells are intimately involved in nerve development and may provide appropriate cell substrates and trophic support for axon outgrowth and guidance. The mammalian olfactory nerve contains a unique type of non-myelinating glial cell, termed the ensheathing cell, with phenotypic traits of both Schwann cells and astrocytes. This nerve is unusual in that following injury, it can regenerate its central projections to the olfactory bulb via replacement of sensory neurons in the olfactory epithelium by basal cells which differentiate into sensory neurons. This regenerative capacity may in part be due to specific environmental cues provided to the growing afferents by the ensheathing cells. Little is currently known about potential trophic actions of ensheathing cells on olfactory axon growth, but studies by the applicant have shown that ensheathing glia in the adult rat olfactory bulb express high levels of the neurotrophic factors basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF). Both of these factors have been implicated in regeneration of peripheral nerve and central axonal sprouting. These data suggest that expression of neurotrophic factors by ensheathing glia may contribute to axon growth in the olfactory system. The goals of the proposed research are to test aspects Of this hypothesis. The first goal is to characterize expression of CNTF, bFGF and acidic FGF in the developing olfactory system to determine if ensheathing cell expression of trophic factors is correlated with outgrowth of developing sensory axons. The second goal will be to determine if olfactory sensory neurons express appropriate receptors for these trophic factors during this time. The third aim is to determine if ensheathing glia and sensory neurons undergo changes in expression of trophic factors and receptors during periods of olfactory nerve degeneration and regeneration in lesioned adult rats. The final aim is to establish cultures of ensheathing glia from the neonatal rat and to characterize expression of trophic factors by these cells in vitro. Results of these studies could provide valuable insights into potential glial-dependent trophic mechanisms which promote nerve growth.