CELLULAR AND MOLECULAR BIOLOGY OF NEURONAL PLASTICITY

Project Details

Description

Candidate: The author is Chief Resident in pediatric neurology at New York
Hospital-Cornell Medical Center with research training in developmental
neuro-science. This award will prepare the author for a career in academic
medicine as an independent investigator in developmental neurology.

Proposal: Recent evidence suggests that neurotransmitter phenotypic
expression is remarkably mutable. This study seeks to define the
extracellular factors and intracellular processes through which sympathetic
neurons regulate multiple transmitter phenotypes. The specific aims are to
define mechanisms through which presynaptic neurons, the central nervous
system and target organ regulate peptide and catecholamine traits,
determine the role of specific messenger RNA (mRNA) in modulation and
expression of catecholamine enzyme, tyrosine hydroxylase (TH), and examine
the roles of neurite outgrowth and extracellular factors in initial
embryonic phenotypic expression.

The superior cervical sympathetic ganglion, serving as a model system of
the multiple transmitter neuron, will be assayed for markers of
catecholamine (TH) and peptide (Substance P, SP) phenotypes in adults and
neonates in vivo and embryos in vitro. The effects of long term
deafferentation on ganglion TH and SP will be defined to examine chronic
regulatory mechanims during maturity and ontogeny. The regulation of
transmitter trait development by central synapses and Nerve Growth Factor
will also be examined. The specific role of mRNA in TH modulation and
expression during maturity and ontogeny, will be defined after altering
extracellular regulatory factors. The rigorous conditions of tissue
culture will permit analysis of cellular and molecular mechanisms in
initial phenotypic expression.

Characterization of the extracellular factors regulating phenotypic
plasticity may lead to therapeutic interventions which can alter deranged
neurologic function and, thus, alleviate symptoms of neural tube
dysgenesis, hereditary ataxias and dystonias and cerebral palsy.
Elucidation of molecular genetic mechanisms of phenotypic expression may
suggest new approaches to degenerative processes such as the spinal
muscular atrophies, Huntington's chorea and lysosomal storage disease.

Environment: The Laboratory of Developmental Neurology is actively
examining classical and peptide neurotransmitter plasticity during
development and maturity, in vivo and in vitro.
StatusFinished
Effective start/end date12/31/8912/31/89

Funding

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development

ASJC

  • Molecular Biology
  • Cell Biology

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