Molecular Specifiers of Neural Cell Plasticity

  • Ojeda, Sergio (PI)

    Project: Research project

    Project Details


    DESCRIPTION (provided by applicant): The initiation of mammalian puberty requires an increased pulsatile secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development, from specialized neurons in the basal hypothalamus. This increase is brought about by changes in the activity of neuronal and astroglial subsets functionally connected to the LHRH neuronal network. Whether such alterations in cell-cell communication are purely biochemical or require plastic rearrangements is not known. This application proposes a combination of cellular, molecular, and genomic approaches to examine the hypothesis that major changes in hypothalamic expression of three novel multigene families of cell-surface molecules recently implicated as critical components of synaptic specification and neuron-glia communication in the central nervous system, underlie the initiation of primate puberty. The demonstration of such changes will provide prima facie evidence for the concept that plastic rearrangements in neuron-to-neuron and glial-neuronal communication are integral components of the neuroendocrine mechanism by which the brain controls the onset of mammalian puberty. To this end, the following specific aims are proposed: 1. To test the hypothesis that coordinated changes in the hypothalamic expression of neurexins -- a recently discovered, multi-product family of cell-surface proteins thought to play a major role in neuronal cell recognition -- occur at the time of primate puberty. 2. To test the hypothesis that hypothalamic-specific changes in the expression of particular members of the novel protocadherin - a family of adhesion-signaling molecules recently implicated in the specification of brain synaptic connectivity, occur at the initiation of puberty. 3. To examine the hypothesis that hypothalamic-specific changes in the expression of a newly discovered family of neurexin-related molecules termed CASPRs (contactin-associated proteins) involved in glial-neuronal communication, and their interacting molecules, occurs at the time of primate puberty, and 4. To test the hypothesis that contactin/CASPR-1 and its astroglial receptor protein tyrosine phosphatase-beta (RPTP-b) mediate adhesive communication between astroglial cells and LHRH neurons, and that this is an event regulated by growth factors involved in the facilitatory control that glial cells exert on LHRH release during female sexual maturation.
    Effective start/end date12/1/0211/30/08


    • National Institutes of Health: $350,300.00
    • National Institutes of Health: $307,862.00
    • National Institutes of Health: $365,050.00
    • National Institutes of Health: $350,300.00


    • Medicine(all)


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