The long term goal of the proposed reserach is to determine the role of gangliosides in neuritogenesis, in order to better understand the basic mechanisms of neuronal development and regeneration. The immediate goals are to: 1) define the role of gangliosides in Nerve Growth Factor (NGF)-mediated neuritogenesis; 2) to investigate the role of gangliosides in NGF-independent trophic interactions and 3) to determine the cytoskeletal basis of ganglioside-enhanced neuronal differentiation. In the remaining twenty-one months of this grant we will: 1) explore the neuritogenic capacities of four major gangliosides (GM1, GD1a, GD1b and GT1b) biochemically and morphologically on primary and established neuronal models in vitro; 2) determine the action of monoclonal antibodies, directed against specific gangliosides, on neuronal differentiation; 3) examine the cytoskeletal basis of ganglioside-mediated neuritogenesis by employing agents which disrupt or stabilize structural components of the neuron and 4) probe the ganglioside distribution and fluidity of neuronal membranes. We will continue studies aimed to examine the relationship between ganglioside-mediated changes in neuronal surface topography, metabolic activity and neuronal elongation. Histochemical and morphological probes, including lectins, toxins, taxol, colcemid and cytochalasin D will be employed in these ongoing studies. We hope that information gained from these in vitro studies will elucidate basic mechanisms essential to neuronal differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024524-02
Application #
3409205
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Louisville
Department
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Fentie, I H; Roisen, F J (1993) The effects of cytoskeletal altering agents on the surface topography of GM1 in neuro-2A neuroblastoma cell membranes. J Neurocytol 22:498-506
Doane, K J; Roisen, F J; Wilson, F J (1992) The effects of nerve growth factor and dibutyryl cyclic AMP on cytoskeletal densities in cultured sensory ganglia. Tissue Cell 24:367-78
Spoerri, P E; Roisen, F J (1992) Cytoskeletal elements regulate the distribution of nerve growth factor receptors in PC12 cells. J Neurosci Res 31:494-501
Gupta, M; Schwarz, J; Chen, X L et al. (1990) Gangliosides prevent MPTP toxicity in mice--an immunocytochemical study. Brain Res 527:330-4
Spoerri, P E; Dozier, A K; Roisen, F J (1990) Calcium regulation of neuronal differentiation: the role of calcium in GM1-mediated neuritogenesis. Brain Res Dev Brain Res 56:177-88
Spoerri, P E; Caple, C G; Roisen, F J (1990) Taurine-induced neuronal differentiation: the influence of calcium and the ganglioside GM1. Int J Dev Neurosci 8:491-503
Spoerri, P E; Roisen, F J (1988) Ganglioside potentiation of NGF-independent trophic agents on sensory ganglia. Neurosci Lett 90:21-6
Spoerri, P E; Rapport, M M; Mahadik, S P et al. (1988) Inhibition of conditioned media-mediated neuritogenesis of sensory ganglia by monoclonal antibodies to GM1 ganglioside. Brain Res 469:71-7
Spoerri, P E; Roisen, F J (1988) Ganglioside potentiation of NGF-independent conditioned medium enhancement of neuritic outgrowth from spinal cord and ciliary ganglia explants. Int J Dev Neurosci 6:223-32
Vertes, R P; Fass, B (1988) Projections between the interpeduncular nucleus and basal forebrain in the rat as demonstrated by the anterograde and retrograde transport of WGA-HRP. Exp Brain Res 73:23-31

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