De Novo Protein Synthesis Mediated by the Eukaryotic Elongation Factor 2 Is Required for the Anxiolytic Effect of Oxytocin.

Détails

ID Serval
serval:BIB_D0FB5B8EDBD2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
De Novo Protein Synthesis Mediated by the Eukaryotic Elongation Factor 2 Is Required for the Anxiolytic Effect of Oxytocin.
Périodique
Biological psychiatry
Auteur(s)
Martinetz S., Meinung C.P., Jurek B., von Schack D., van den Burg E.H., Slattery D.A., Neumann I.D.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Statut éditorial
Publié
Date de publication
15/05/2019
Peer-reviewed
Oui
Volume
85
Numéro
10
Pages
802-811
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The neuropeptide oxytocin (OXT) mediates its actions, including anxiolysis, via its G protein-coupled OXT receptor. Within the paraventricular nucleus of the hypothalamus (PVN), OXT-induced anxiolysis is mediated, at least in part, via activation of the mitogen-activated protein kinase pathway following calcium influx through transient receptor potential cation channel subfamily V member 2 channels. In the periphery, OXT activates eukaryotic elongation factor 2 (eEF2), an essential mediator of protein synthesis.
In order to study whether OXT activates eEF2 also in neurons to exert its anxiolytic properties in the PVN, we performed in vivo and cell culture experiments.
We demonstrate that OXT, in a protein kinase C-dependent manner, activates eEF2 both in a hypothalamic cell line and in vivo within the PVN. Next, we reveal that OXT stimulates de novo protein synthesis, while inhibition of protein synthesis within the PVN prevents the anxiolytic effect of OXT in male rats. Moreover, activation of eEF2 within the PVN conveyed an anxiolytic effect supporting a role of OXT-induced eEF2 activation and protein synthesis for its anxiolysis. Finally, we show that one of the proteins that is upregulated by OXT is the neuropeptide Y receptor 5. Infusion of a specific neuropeptide Y receptor 5 agonist into the PVN consequently led to decreased anxiety-related behavior, while pretreatment with a neuropeptide Y receptor 5 antagonist prevented the anxiolytic effect of OXT.
Taken together, these results show that OXT recruits several intracellular signaling cascades to induce protein synthesis, which mediates the anxiolytic effects of OXT within the PVN and suggests that eEF2 represents a novel target for anxiety-related disorders.
Mots-clé
Animals, Anti-Anxiety Agents/administration & dosage, Anti-Anxiety Agents/metabolism, Anxiety/metabolism, Cells, Cultured, Down-Regulation, Eukaryotic Initiation Factor-2/metabolism, MAP Kinase Signaling System, Male, Oxytocin/administration & dosage, Oxytocin/metabolism, Paraventricular Hypothalamic Nucleus/drug effects, Paraventricular Hypothalamic Nucleus/metabolism, Protein Kinase C/metabolism, Rats, Wistar, Receptors, Neuropeptide Y/metabolism, Up-Regulation, Anxiety, De novo protein synthesis, NPY5R, Oxytocin, PVN, eEF2
Pubmed
Web of science
Création de la notice
14/03/2019 10:12
Dernière modification de la notice
27/04/2020 6:20
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