Project: Research project

Project Details


Our laboratory has made the initial observations suggesting that
endogenous opioid peptides are related to nervous system
development, and that perturbations of endogenous opioid/opioid
receptor interactions markedly influence the course of
neuroontogeny (Science 221:1179-1180, 1983). During the first 2
years of this project, the role of endogenous opioid systems in
brain development has been carefully defined. We found that
endogenous opioids modulate neurobiological maturation, and
influence both cell proliferation, and differentiation. A major
discovery was that endogenous opioid systems are involved in human
brain development. Our hypothesis is that endogenous opioids serve
to control brain development through interaction with opioid
receptors associated with developing neural cells; this may reflect
an autocrine mechanism of growth. In this grant proposal, we
continue to explore this thesis using the developing rat cerebella,
as a model. The aims of this proposal are: (1) Identify the
prototypic opioids related to growth through drug displacement
studies and structure-function experiments. The binding site
related to growth will be fully characterized, including assessment
of kinetics, saturation, and interactions. (2) determine the
location and distribution of growth-related opioids by
immunoelectron microscopy. (3) Investigate whether developing
neural tissues synthesize opioid precursors using in situ
hybridization. (4) Isolate and identify the opioid receptor related
to neural growth, and characterize the receptor in terms of size,
subunit composition, peptide maps, and binding function as studied
by reconstitution experiments. Our research efforts will
contribute to comprehending normal brain development, and will have
impact on understanding the etiology or neurodevelopmental-based
dysfunction. Information derived from these studies may be used
in designing strategies for intervention in some developmental
disorders of the nervous system. This research is part of a long-
range program in cellular and molecular neurobiology which seeks
to understand the fundamental principles underlying normal and
abnormal brain development.
Effective start/end date1/1/901/1/90


  • National Institute of Neurological Disorders and Stroke

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