BRAIN DEVELOPMENT AND ENDOGENOUS OPIOID SYSTEMS

Project: Research project

Description

Our laboratory has made the initial observations suggesting that
endogenous opioid systems are related to nervous system development, and
that perturbations of neuro-ontogeny (Science 221:1179-1180, 1983).
During the past 8 years of this project the role of endogenous opioid
systems in brain development has been carefully defined. We have
identified [Met]-enkephalin, derived from preproenkephalin A (PPE), as
the native peptide that serves as
an opioid growth factor (OGF). OGF regulates the proliferation of both
neuronal and glial precursors through inhibitory channels. The source
of this peptide appears to be both autocrine (germinative cells) and
paracrine (macronneurons). OGF interacts with the nuclear-associated
zeta opioid receptor to regulate growth. The binding subunits have been
identified and characterized, and polyclonal and monoclonal antibodies
generated to these polypeptides. In this grant proposal, we continue to
explore the thesis that an endogenous opioid system is important to
neurrobiological development. The aims of this proposal are: (1)
Determine the embryogenesis of OGF and PPE gene expression in the rat
brain by immunocytochemistry, Northern analysis and in situ
hybridization. (2) Define the ontogeny of the zeta receptor
quantitatively (immunodot assay) and qualitatively (Western blotting and
peptide mapping). (3) Ascertain the location of the zeta receptor by
immunocytochemistry, immunoelectron microscopy, and in vitro
autoradiography. (4) Isolate, purify, and characterize the native zeta
receptor, and assess binding function by reconstitution experiments.
(5) Clone and sequence the cDNA for the zeta receptor. (6) Examine the
OGF and zeta receptor in developing human brain using
immunocytochemistry, in vitro autoradiography, Western and ligand
blotting, Northern analysis, and in situ hybridization. This research
will contribute to comprehending the processes shaping normal brain
development, and should be useful in understanding the etiology of
developmentally-based neurobiological dysfunction. This research is part
of a long-range program in cellular and molecular neurobiology which
seeks to define the fundamental principles underlying normal and abnormal
brain development.
StatusFinished
Effective start/end date9/1/848/31/98

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $192,069.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $208,302.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Opioid Analgesics
Brain
Neurobiology
Opioid Receptors
Growth
Organized Financing
Intercellular Signaling Peptides and Proteins
Endorphins
Nervous System
Peptides
Autoradiography
Research
Opiate Alkaloids
Cerebellum
Opioid Peptides
Methionine Enkephalin
Immunohistochemistry
Immunoelectron Microscopy
In Situ Hybridization
Cell Differentiation