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Guillebaud F, Girardet C, Abysique A, et al. Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level. Front Neurosci. 2017;11:308doi: 10.3389/fnins.2017.00308.
Guillebaud, F., Girardet, C., Abysique, A., Gaigé, S., Barbouche, R., Verneuil, J., Jean, A., Leprince, J., Tonon, M. C., Dallaporta, M., Lebrun, B., & Troadec, J. D. (2017). Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level. Frontiers in neuroscience, 11308. https://doi.org/10.3389/fnins.2017.00308
Guillebaud, Florent, et al. "Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level." Frontiers in neuroscience vol. 11 (2017): 308. doi: https://doi.org/10.3389/fnins.2017.00308
Guillebaud F, Girardet C, Abysique A, Gaigé S, Barbouche R, Verneuil J, Jean A, Leprince J, Tonon MC, Dallaporta M, Lebrun B, Troadec JD. Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level. Front Neurosci. 2017 May 30;11:308. doi: 10.3389/fnins.2017.00308. eCollection 2017. PMID: 28611581; PMCID: PMC5447764.
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Front Neurosci. 2017 May 30;11:308. doi: 10.3389/fnins.2017.00308. eCollection 2017.

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level.

Frontiers in neuroscience

Florent Guillebaud, Clémence Girardet, Anne Abysique, Stéphanie Gaigé, Rym Barbouche, Jérémy Verneuil, André Jean, Jérôme Leprince, Marie-Christine Tonon, Michel Dallaporta, Bruno Lebrun, Jean-Denis Troadec

Affiliations

  1. Laboratoire Physiologie et Physiopathologie du Système Nerveux Somato-Moteur et Neurovégétatif EA 4674, Faculté des Sciences et Techniques de St Jérôme, Université Aix-MarseilleMarseille, France.
  2. Institut National de la Santé et de la Recherche Médicale U1239, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Institute for Research and Innovation in Biomedicine, University of Rouen NormadieMont-Saint-Aignan, France.

PMID: 28611581 PMCID: PMC5447764 DOI: 10.3389/fnins.2017.00308

Abstract

Endozepines are endogenous ligands for the benzodiazepine receptors and also target a still unidentified GPCR. The endozepine octadecaneuropeptide (ODN), an endoproteolytic processing product of the diazepam-binding inhibitor (DBI) was recently shown to be involved in food intake control as an anorexigenic factor through ODN-GPCR signaling and mobilization of the melanocortinergic signaling pathway. Within the hypothalamus, the DBI gene is mainly expressed by non-neuronal cells such as ependymocytes, tanycytes, and protoplasmic astrocytes, at levels depending on the nutritional status. Administration of ODN C-terminal octapeptide (OP) in the arcuate nucleus strongly reduces food intake. Up to now, the relevance of extrahypothalamic targets for endozepine signaling-mediated anorexia has been largely ignored. We focused our study on the dorsal vagal complex located in the caudal brainstem. This structure is strongly involved in the homeostatic control of food intake and comprises structural similarities with the hypothalamus. In particular, a circumventricular organ, the area postrema (AP) and a tanycyte-like cells forming barrier between the AP and the adjacent nucleus tractus solitarius (NTS) are present. We show here that DBI is highly expressed by ependymocytes lining the fourth ventricle, tanycytes-like cells, as well as by proteoplasmic astrocytes located in the vicinity of AP/NTS interface. ODN staining observed at the electron microscopic level reveals that ODN-expressing tanycyte-like cells and protoplasmic astrocytes are sometimes found in close apposition to neuronal elements such as dendritic profiles or axon terminals. Intracerebroventricular injection of ODN or OP in the fourth ventricle triggers c-Fos activation in the dorsal vagal complex and strongly reduces food intake. We also show that, similarly to leptin, ODN inhibits the swallowing reflex when microinjected into the swallowing pattern generator located in the NTS. In conclusion, we hypothesized that ODN expressing cells located at the AP/NTS interface could release ODN and modify excitability of NTS neurocircuitries involved in food intake control.

Keywords: area postrema; astrocytes; dorsal vagal complex; food intake; nucleus of the tractus solitarius; octadecaneuropeptide; swallowing; tanycytes

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