Gangliosides have been found to enhance neuritogenesis by neuroblastoma cel s in vitro , and to enhance nerve regeneration in vivo. Recently the oligosaccharide moieties of gangliosides have also been found to enhance neuritogenesis by neuroblastoma cells, suggesting the presence of a cell surface receptor. This hypothesis is supported by the observation that viab e neural retina cells can bind to gangliosides adsorbed to plastic via a trypsin sensitive mechanism. This proposal asks two fundamental questions concerning these observations: 1) how much exogenous ganglioside actually reaches the lesioned area within the brain where it putatively enhances neuritogenesis?; and 2) how does the ganglioside interact with the neuroblastoma or neuron? To answer the first question autoradiographic experiments will be carried out to determine the distribution of labeled ganglioside in the brains of lesioned and unlesioned rats. To answer the second question, experiments will be carried out to determine whether ganglioside responsive neuroblastoma cells have cell surface receptors capable of recognizing the oligosaccharide moiety of the appropriate gangli - side. If receptors are identified they will be isolated and characterized. Primary cultures of neurons will also be assayed for the presence of ganglioside-oligosaccharide cell surface receptors. To determine the effect of this interaction on """"""""differentiation"""""""" properties defined as associated with neuronal maturation will be monitored. To determine a possible mechani m for transmitting the binding into an intracellular response, the effect of the ganglioside and the corresponding oligosaccharide on the phosphorylatio activity of the cell plasma membranes will be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS026126-01A2
Application #
3411781
Study Section
Neurology C Study Section (NEUC)
Project Start
1989-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Fiala, M; Gujuluva, C; Berger, O et al. (2001) Chemokine receptors on brain endothelia--keys to HIV-1 neuroinvasion? Adv Exp Med Biol 493:35-40
Berger, O; Gan, X; Gujuluva, C et al. (1999) CXC and CC chemokine receptors on coronary and brain endothelia. Mol Med 5:795-805
Zhang, L; Looney, D; Taub, D et al. (1998) Cocaine opens the blood-brain barrier to HIV-1 invasion. J Neurovirol 4:619-26
Schengrund, C L; Mummert, C M (1998) Exogenous gangliosides. How do they cross the blood-brain barrier and how do they inhibit cell proliferation. Ann N Y Acad Sci 845:278-84
Mummert, C M; Schengrund, C L (1997) Nonmuscle myosin heavy chain B is recognized by a monoclonal antibody that inhibits GM1-enhanced neuritogenesis. J Neurochem 68:596-600
Schengrund, C L (1995) Evidence that molecules on the surface of one cell can adhere to the oligosaccharide portion of gangliosides on the surface of another cell. Biol Signals 4:1-13
Saulino, M F; Schengrund, C L (1994) Differential accumulation of gangliosides by the brains of MPTP-lesioned mice. J Neurosci Res 37:384-91
Saulino, M F; Schengrund, C L (1993) Effects of specific gangliosides on the in vitro proliferation of MPTP-susceptible cells. J Neurochem 61:1277-83
Fueshko, S M; Schengrund, C L (1992) Identification of a GM1-binding protein on the surface of murine neuroblastoma cells. J Neurochem 59:527-35
Fueshko, S M; Schengrund, C L (1990) Murine neuroblastoma cells express ganglioside binding sites on their cell surface. J Neurochem 54:1791-7

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