Neuroanatomical and Phenotypical Characterization of Amylin's Central Signaling Pathways

Abstract

Event Abstract Back to Event Neuroanatomical and Phenotypical Characterization of Amylin's Central Signaling Pathways C. S. Potes1*, T. Riediger1 and T. A. Lutz1 1 Zurich Center Integrative Human Physiology, Zurich University, Institute of Veterinary Physiology, Switzerland Pancreatic amylin inhibits food intake via activation of the area postrema (AP). This activation is synaptically transmitted to the nucleus of the solitary tract (NTS), lateral parabrachial nucleus (LPB), central amygdaloid nucleus (Ce) and bed nucleus of stria terminalis (BST). The nature of AP neurons mediating amylin’s anorectic effect is unknown. Most amylin-activated AP neurons are noradrenergic (NA), i.e. they express dopamine-beta-hydroxylase (DBH). Hence, we first hypothesized that NA-neurons mediate amylin’s effects. Further, the pathways involved in amylin signaling are not fully identified, especially those mediating an inhibition of the lateral hypothalamic area (LHA) neurons that are activated by 24h of fasting. Therefore we designed a second study to investigate the brain pathways involved in amylin signaling.First, we performed a targeted lesion of AP NA-neurons using a saporin conjugated to an antibody against DBH (DSAP). DSAP-treated and sham lesioned rats were tested for amylin’s effect to reduce eating and to induce neuronal activation using c-Fos protein expression as a marker. Second, we used retrograde (cholera toxin B) and anterograde (biotinylated dextran amine) tracing to identify neuronal projections from amylin- activated brain areas to the LHA.In contrast to sham lesioned animals, NA-lesioned rats showed no amylin-induced suppression of food intake. Further, amylin-induced c-Fos in the AP/NTS region was lower in NA-lesioned rats. Second, we showed that 33% of amylin-activated (c-Fos positive) neurons in the LPB project to the LHA. Only 9% and 7% of amylin- activated neurons from NTS and BST, respectively, project to the LHA. No projections from the AP and Ce were found. Besides the projections within the AP-BST axis, we further identified dense LPB efferents to the ventromedial and paraventricular hypothalamic nuclei.In conclusion, we found functional and neurophysiological evidence for an involvement of AP NA-neurons in the mediation of amylin's anorectic effect. The LPB appears to be the main relay for the amylin signal from AP/NTS to the LHA, mediating the amylin-induced inhibition of LHA. In addition to conveying excitatory input from the AP/NTS to the Ce and BST, the amylin-activated LPB area also projects to other hypothalamic feeding areas that may be involved in amylin’s anorectic action. A detailed knowledge of amylin’s central mode of action is important for clinical use of amylin analogues in the treatment of obesity. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Citation: Potes CS, Riediger T and Lutz TA (2009). Neuroanatomical and Phenotypical Characterization of Amylin's Central Signaling Pathways. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.040 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Aug 2009; Published Online: 06 Aug 2009. * Correspondence: C. S Potes, Zurich Center Integrative Human Physiology, Zurich University, Institute of Veterinary Physiology, Zurich, Switzerland, cpotes@vetphys.uzh.ch Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers C. S Potes T. Riediger T. A Lutz Google C. S Potes T. Riediger T. A Lutz Google Scholar C. S Potes T. Riediger T. A Lutz PubMed C. S Potes T. Riediger T. A Lutz Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.