Project Details


While abundant studies have begun to elucidate ontogeny of the peripheral
nervous system, molecular mechanisms underlying brain development remain
obscure. This is due in part to the complexity and inaccessibility of the
central nervous system (CNS), particularly in developing animals. We,
however, are now able to approach questions of developmental regulation in
the CNS. We have succeeded in growing brain nuclei in an accessible tissue
culture environment and are able to couple study of these nuclei in vitro
with sensitive biochemical and morphological techniques. We can thus
define molecular events associated with central neuron development. In
particular, we have cultured the brain noradrenergic nucleus locus
coeruleus. In culture locus neurons express a variety of noradrenergic
traits, including endogenous catecholamine (CA), the specific uptake
mechanism for norepinephrine (NE) and the CA biosynthetic enzymes, tyrosine
hydroxylase and dopamine-Beta-hydroxylase. We thus can use these CA traits
to define factors that regulate development of central neurons and
determine whether similar rules govern central and peripheral ontogeny.
Influences we will study include those of presynaptic depolarizing agents
and target tissues. In addition, we will determine the role of
glucocorticoids in expression of NE characters. Finally, we will compare
regulation of expression of dopamine characters in developing substantia
nigra with expression of noradrenergic characters in the locus. These
experiments hopefully will provide insight into sites where changes in the
normal milieu of a maturing neuron may lead to abnormal brain development.
Such an understanding may eventually lead to new therapeutic approaches to
congenital birth defects, such as mental retardation and neural tube
Effective start/end date12/31/8912/31/89


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


  • Neuroscience(all)


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