Ganglioside transport within and between brain cells continues to be a major theme of our research. Having previously established that fast anterograde transport is the mechanism for transfer of gangliosides from the cell body (where they are synthesized) to axonal and nerve-ending membranes, we are now studying retrograde transport. We are using the double-ligation paradigm with motoneurons of the rat sciatic nerve, and observe fast retrograde transport of both gangliosides and glycoproteins. Our next objective is to compare molecular species moving in the anterograde and retrograde directions, both in normal and regenerating nerve. Detailed structure analysis will be carried out for gangliosides of motor and sensory neurons, capitalizing on the specific radio-labeling that arises from use of different injection sites. Preliminary data indicate another mode of ganglioside transport in brain - that which is catalyzed by a gnaglioside (glycolipid) transfer protein. We shall study this protein and its ability to catalyze ganglioside movement between neural membranes and between cells. The nature and origin of astrocytic gangliosides remains a paradox which we shall attempt to solve through a variety of approaches; one possibility being considered is that gangliosides are transferred to astrocytes from neurons, possibly through mediation of the transfer protein. The neuritogenic effect of gangliosides will be studied employing primary cultures of increasing complexity: pure neurons, mixed neurons and glia, and organotypic cultures. These will serve as models for probing the role which gangliosides may have in neuronal differentiation. We shall compare the effects of many different gangliosides, added alone and in the presence of the transfer protein which is expected to significantly alter the ganglioside composition of the neuronal membrane. Finally, we shall determine the lipid profile of growth cone membranes with special emphases on gangliosides and neutral glycosphingolipids.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS004834-23
Application #
3393346
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1978-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
23
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Wu, G; Lu, Z H; Ledeen, R W (1996) GM1 ganglioside modulates prostaglandin E1 stimulated adenylyl cyclase in neuro-2A cells. Glycoconj J 13:235-9
Wu, G; Lu, Z H; Nakamura, K et al. (1996) Trophic effect of cholera toxin B subunit in cultured cerebellar granule neurons: modulation of intracellular calcium by GM1 ganglioside. J Neurosci Res 44:243-54
Wu, G; Fan, S F; Lu, Z H et al. (1995) Chronic opioid treatment of neuroblastoma x dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents. J Neurosci Res 42:493-503
Wu, G; Lu, Z H; Ledeen, R W (1995) Induced and spontaneous neuritogenesis are associated with enhanced expression of ganglioside GM1 in the nuclear membrane. J Neurosci 15:3739-46
Wu, G; Ledeen, R W (1994) Gangliosides as modulators of neuronal calcium. Prog Brain Res 101:101-12
Wu, G; Nakamura, K; Ledeen, R W (1994) Inhibition of neurite outgrowth of neuroblastoma Neuro-2a cells by cholera toxin B-subunit and anti-GM1 antibody. Mol Chem Neuropathol 21:259-71
Ledeen, R W; Diebler, M F; Wu, G et al. (1993) Ganglioside composition of subcellular fractions, including pre- and postsynaptic membranes, from Torpedo electric organ. Neurochem Res 18:1151-5
Nakamura, K; Wu, G; Ledeen, R W (1992) Protection of neuro-2a cells against calcium ionophore cytotoxicity by gangliosides. J Neurosci Res 31:245-53
Wu, G S; Lu, Z H; Ledeen, R W (1991) Correlation of gangliotetraose gangliosides with neurite forming potential of neuroblastoma cells. Brain Res Dev Brain Res 61:217-28
Shen, K F; Crain, S M; Ledeen, R W (1991) Brief treatment of sensory ganglion neurons with GM1 ganglioside enhances the efficacy of opioid excitatory effects on the action potential. Brain Res 559:130-8

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