The Effects of Apelin on the Electrical Activity of Hypothalamic Magnocellular Vasopressin and Oxytocin Neurons and Somatodendritic Peptide Release

Apelin, a novel peptide originally isolated from bovine stomach tissue extracts, is widely but selectively distributed throughout the nervous system. Vasopressin and oxytocin are synthesised in the magnocellular neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN), which are apelin-rich regions in the central nervous system. We made extracellular electrophysiological recordings from the transpharyngeally exposed SON of urethane-anaesthetised rats to assess the role of apelin in the control of the firing activity of identified magnocellular vasopressin and oxytocin neurons in vivo. Apelin-13 administration onto SON neurons via microdialysis revealed cell-specific responses; apelin-13 increased the firing rates of vasopressin cells, but had no effect on the firing rate of oxytocin neurons. A direct excitatory effect of apelin-13 on vasopressin cell activity is also supported by our in vitro studies showing depolarisation of membrane potential and increase in action potential firing. To assess the effects of apelin-13 on somato/dendritic peptide release we used in vitro release studies from SON explants in combination with highly sensitive and specific radioimmunoassays. Apelin-13 decrease basal (by 78%, p<0.05, n=6) and potassium-stimulated (by 57%, p<0.05, n=6) vasopressin release but had no effect on somato/dendritic oxytocin release. Taken together, our data suggest a local autocrine feedback action of apelin on magnocellular vasopressin neurons. Furthermore, these data show a marked dissociation between axonal and dendritic vasopressin release with a decrease in somato/dendritic release but an increase in electrical activity at the cell bodies, indicating that release from these two compartments can be regulated wholly independently

3D Distribution of Tyrosine Hydroxylase, Vasopressin and Oxytocin Neurons in the Transparent Postnatal Mouse Brain

International audienceOver the years, advances in immunohistochemistry techniques have been a critical step in detecting and mapping neuromodulatory substances in the central nervous system. The better quality and specificity of primary antibodies, new staining procedures and the spectacular development of imaging technologies have allowed such progress. Very recently, new methods permitting tissue transparency have been successfully used on brain tissues. In this work, we combined whole-mount immunostaining for tyrosine hydroxylase (TH), oxytocin (OXT) and arginine vasopressin (AVP), with iDISCO+ clearing method, light-sheet microscopy and semi automated counting of 3D-labelled neurons to obtain a 3D distribution of these neuronal populations in a 5-day postnatal (P5) mouse brain. Segmentation procedure and 3D reconstruction allowed us to map with high resolution TH staining the various catecholaminergic cell groups and their ascending and descending fiber pathways. We show that TH pathways are present in the whole P5 mouse brain, similar to what was observed in the adult rat brain

Three-dimensional distribution of tyrosine hydroxylase, vasopressin and oxytocin neurones in the transparent postnatal mouse brain

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The RFamide neuropeptide 26RFa and its role in the control of neuroendocrine functions

International audienceIdentification of novel neuropeptides and their cognate G protein-coupled receptors is essential for a better understanding of neuroendocrine regulations. The RFamide peptides represent a family of regulatory peptides that all possess the Arg-Phe-NH2 motif at their C-terminus. In mammals, seven RFamide peptides encoded by five distinct genes have been characterized. The present review focuses on 26RFa (or QRFP) which is the latest member identified in this family. 26RFa is present in all vertebrate phyla and its C-terminal domain (KGGFXFRF-NH2), which is responsible for its biological activity, has been fully conserved during evolution. 26RFa is the cognate ligand of the orphan G protein-coupled receptor GPR103 that is also present from fish to human. In all vertebrate species studied so far, 26RFa-expressing neurons show a discrete localization in the hypothalamus, suggesting important neuroendocrine activities for this RFamide peptide. Indeed, 26RFa plays a crucial role in the control of feeding behavior in mammals, birds and fish. In addition, 26RFa up-regulates the gonadotropic axis in mammals and fish. Finally, evidence that the 26RFa/GPR103 system regulates steroidogenesis, bone formation, nociceptive transmission and arterial blood pressure has also been reported. Thus, 26RFa appears to act as a key neuropeptide in vertebrates controlling vital neuroendocrine functions. The pathophysiological implication of the 26RFa/GPR103 system in human is totally unknown and some fields of investigation are proposed