The goal of these studies is to understand the mechanisms by which neuropeptide biosynthesis and processing are regulated at a biochemical level in the central nervous system. Such knowledge is essential to an understanding of the roles which neuropeptides play in neural integration, since a variety of peptides can be derived from the transcription of a given neuropeptide gene. As a model system, we will study the neurons which synthesize the neuropeptides vasopressin and oxytocin and their precursors in the projection from the paraventricular nucleus to the neural lobe. At the peptide level, we will define the dynamics of the biosynthesis, processing and transport of these neuropeptide systems by in vivo pulse-labeling studies and protein chemical methods. We will also study in vitro the levels of messenger RNA for these neuropeptides in the paraventricular nucleus by hybridization to specific deoxyoligonucleotide probes, and by cell free translation of precursors to the neuropeptides from the mRNA. Finally, we will investigate by protein biosynthetic and nucleic acid probe hybridization studies whether 2 neuropeptide genes known to exist in the same neuron--those for vasopressin and dynorphin in one subset of paraventricular neurons, and those for oxytocin and enkephalin in another sub-et of paraventricular neurons--are independently or coordinately regulated. These studies will add to our understanding of the regulatory mechanisms operative in CNS neurons which produce peptide neurotransmitters. As such, they will provide a basis for investigating whether aberrations in biosynthesis and processing in peptidergic neurons are responsible for, or associated with, neurodegenerative and psychiatric disorders in which peptides are implicated.
| White, J D; Gall, C M; McKelvy, J F (1987) Enkephalin biosynthesis and enkephalin gene expression are increased in hippocampal mossy fibers following a unilateral lesion of the hilus. J Neurosci 7:753-9 |
| White, J D; Krause, J E; McKelvy, J F (1986) In vivo biosynthesis and transport of oxytocin, vasopressin and neurophysin from the hypothalamus to the spinal cord. Neuroscience 17:133-40 |
| White, J D; Stewart, K D; McKelvy, J F (1986) Measurement of neuroendocrine peptide mRNA in discrete brain regions. Methods Enzymol 124:548-60 |
| White, J D; Gall, C M; McKelvy, J F (1986) Proenkephalin is processed in a projection-specific manner in the rat central nervous system. Proc Natl Acad Sci U S A 83:7099-103 |
| White, J D; McKelvy, J F (1986) Enkephalin biosynthesis and processing during lactation. Neuroendocrinology 43:377-82 |
