RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior
Autor: | Anna Blasiak, Maria Vittoria Micioni Di Bonaventura, Carlo Cifani, Anna Gugula, Patryk Sambak, Ewa Błasiak, Grzegorz Hess, Agata Szlaga, Andrew L. Gundlach, Alan Kania, Mohammad Akhter Hossain |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty Potassium Channels Receptors Peptide relaxin-3 Neuropeptide Nerve Tissue Proteins Biology Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine binge eating Internal medicine Orexigenic medicine Animals Bulimia Receptor Research Articles RXFP3 Neurons Sex Characteristics Behavior Animal Binge eating General Neuroscience Relaxin digestive oral and skin physiology Feeding Behavior M-like current Rats 030104 developmental biology Endocrinology Oxytocin Paraventricular nucleus of hypothalamus paraventricular nucleus of hypothalamus Magnocellular cell Female medicine.symptom Relaxin-3 hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Cellular/Molecular Paraventricular Hypothalamic Nucleus Signal Transduction medicine.drug |
Zdroj: | The Journal of Neuroscience |
ISSN: | 1529-2401 0270-6474 |
Popis: | Binge-eating disorder is the most common eating disorder. Various neuropeptides play important roles in the regulation of feeding behavior, including relaxin-3 (RLN3), which stimulates food intake in rats through the activation of the relaxin-family peptide-3 receptor (RXFP3). Here we demonstrate that a likely mechanism underlying the orexigenic action of RLN3 is RXFP3-mediated inhibition of oxytocin- and arginine-vasopressin-synthesizing paraventricular nucleus (PVN) magnocellular neurosecretory cells. Moreover, we reveal that, in male and female rats, this action depends on M-like potassium conductance. Notably, higher intra- and peri-PVN RLN3 fiber densities were observed in females, which may constitute an anatomic substrate for observed sex differences in binge-eating disorder. Finally, in a model of binge-eating in female rats, RXFP3 blockade within the PVN prevented binge-eating behavior. These data demonstrate a direct RLN3/RXFP3 action in the PVN of male and female rats, identify the associated ionic mechanisms, and reveal that hypothalamic RLN3/RXFP3 signaling regulates binge-eating behavior. SIGNIFICANCE STATEMENT Binge-eating disorder is the most common eating disorder worldwide, affecting women twice as frequently as men. Various neuropeptides play important roles in the regulation of feeding behavior, including relaxin-3, which acts via the relaxin-family peptide-3 receptor (RXFP3). Using a model of binge-eating, we demonstrated that relaxin-3/RXFP3 signaling in the hypothalamic paraventricular nucleus (PVN) is necessary for the expression of binge-eating behavior in female rats. Moreover, we elucidated the neuronal mechanism of RLN3/RXFP3 signaling in PVN in male and female rats and characterized sex differences in the RLN3 innervation of the PVN. These findings increase our understanding of the brain circuits and neurotransmitters involved in binge-eating disorder pathology and identify RXFP3 as a therapeutic target for binge-like eating disorders. |
Databáze: | OpenAIRE |
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