Neuropeptide B/neuropeptide W: Characterization of a novel neuropeptide system

The aim of studies presented in this dissertation is to further our knowledge of a novel neuropeptide system, the NPB/NPW system.; The study in Chapter 2 utilizes in situ hybridization and in situ binding techniques to provide a detailed anatomical map of the NPB/NPW system in the rat brain. NPW precursor mRNA is expressed at non-detectable levels, NPB precursor mRNA is expressed primarily at low levels, and GPR7 mRNA is expressed in several regions including the amygdala, suprachiasmatic and ventral tuberomamillary nuclei in the adult rat brain. In situ binding analysis reveal that the vast majority of nuclei that show NPB/NPW binding overlap with the location of GPR7 mRNA expression. This strong overlap suggests that these receptors are postsynaptic. This study sets the stage for understanding the NPB/NPW system in various behavioral paradigms.; Studies in Chapter 3 further our understanding of the role of the NPB/NPW system in pain. Based on previous studies where NPB or NPW administration attenuates allodynia, the expression of NPB/NPW system components were investigated in a model of tactile allodynia. Using in situ hybridization techniques no detectable changes were found in mRNA levels of the components of the NPB/NPW system in rat spinal cord and dorsal root ganglia in response to allodynia. As control, robust changes in calcitonin-gene-related peptide (CGRP) mRNA levels, known to be modulated by allodynia, were found in these tissues. These data suggest that the known attenuation of allodynia by NPB and NPW is mediated either peripherally or supraspinally and not through regulation of the system in either the spinal cord or the dorsal root ganglia.; The results presented in Chapter 2 raised the question of why two such structurally- and pharmacologically-similar peptides, NPB and NPW, are necessary to this system. Chapter 4 details the ontogeny of the NPB/NPW system in the developing rat brain from embryonic day 17 to postnatal day 68. Based on our anatomical localizations, we speculate that the purpose of two such similar peptides may have to do with their differential roles in development. In the infantile period of development only NPW precursor mRNA is present and poised to activate GPR7. During the juvenile developmental period both NPW and NPB precursor mRNA are present to activate GPR7. Following the juvenile period only NPB precursor mRNA is expressed in the brain and therefore it is NPB alone that exerts modulatory effects on GPR7 in the adult rat brain.