The common objective of these projects is to exploit and test the various clues that have recently come to light on the functions of gangliosides in the nervous system. Thus, our recent discovery that gangliosides are present at relatively high levels in synaptic vesicles of Torpedo (and possibly other species) provides an opportunity to investigate their role in neurosecretion. As a first step we shall determine the structures and distributional pattern of molecular species in this organelle and compare them to the structures and distributional pattern of pre-synaptic membrane from the same source. The neuritogenic effect which exogenous gangliosides assert on cultured neurons and certain neuronally- derived cells lines will be studied from the standpoint of mechanism and also by comparing the ganglioside patterns and synthesis potential of responding vs non-responding cells. We shall attempt to determine which pool of exogenous gangliosides causes the effect. These studies will probe the role of differentiation-associated gangliosides in the normal differentiation of neurons. We shall continue our study of gangliosides of the peripheral nervous system, testing our hypothesis that ganglio-type structures are common to all neurons of the CNS and PNS. This system will also be used to study ganglioside role(s) in regeneration. The two ganglioside transfer proteins we have isolated from calf brain will be further purified and characterized as to glycolipid specificity. Their cellular and subcellular localization within brain will be studied by use of antibodies. We shall explore their use as research tools for modifying glycolipid composition of membranes. This will include examination of possible heterogeneity of composition in such membranes from different brain regions and different neuronal types. Using cell culture systems, we shall determine whether growth cone membranes have unique gangliosides not characteristics of the remainder of the differentiating neuron.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology B Subcommittee 2 (NEUB)
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Albert Einstein College of Medicine
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United States
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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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