NEUTRAL GLYCOSPHINGOLIPIDS OF DEVELOPING NERVOUS SYSTEM

Project Details

Description

Glycoconjugates are the major components of the external
glycocalyx of cells and, to a large extent, determine their surface
properties. Lipid glycoconjugates predominate in the nervous
system, and of these the gangliosides have been the major focus
of interest (aside from cerebroside of myelin). This application is
designed to fill a major gap in this area by beginning a systematic
study of neutral glycosphingolipids (GSLs), particularly in the
developing nervous system where recent studies have shown these
substances to be considerably more prominent than had been
previously recognized. Furthermore, they undergo marked
changes as development progresses. We shall begin with a study
of whole brain of 2 species --rat and chicken -- and characterize
the types and quantities of neutral GSLs at various stages of
embryonic and perinatal growth. This should provide an
abundance of neutral GSLs for structural characterization,
thereby laying the groundwork for more detailed studies of
individual cell types in culture. Primary cultures of neurons,
astrocytes and oligodendroglia will be obtained from rat and chick
brain and neutral GSLs labeled to determine molecular patterns of
each cell type at various stages of development. Growth cone
membranes, isolated from embryonic rat brain by a recently
developed procedure, were found to have appreciable neutral
GSLs, and further characterization of these substances will be a
major objective. We intend to follow up a recent discovery of our
group that sensory neurons of rat sciatic nerve contain a
considerable amount of neutral GSLs (in addition to gangiosides) -
- the only such example to date for mature neurons; use of
radiolabeling techniques and the fact that these substances
undergo axonal transport will assist us in identifying these
substances. The biological role of neutral GSLs will be examined
in various ways: (a) observation of developmental changes in vivo
and in vitro, (b) insertion of these lipids into membranes of neural
cells in vitro, to determine their effect on development, and (c)
the use of interventive agents (e.g. antibodies) to hinder
development at specific stages. Insertion into membranes will be
aided by glycolipid transfer proteins, now being isolated and
characterized in our laboratory. Further study of such proteins
will be part of this project.
StatusFinished
Effective start/end date12/31/8912/31/91

Funding

  • 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)
  • Immunology

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