STUDY OF NERVOUS SYSTEM GANGLIOSIDES AND RELATED LIPIDS

Project Details

Description

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.
StatusFinished
Effective start/end date12/31/8911/30/94

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

ASJC

  • Medicine(all)
  • Neuroscience(all)
  • Cell Biology

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