Martinetz, Stefanie and Meinung, Carl-Philipp and Jurek, Benjamin and von Schack, David and van den Burg, Erwin H. and Slattery, David A. and Neumann, Inga D. (2019) De Novo Protein Synthesis Mediated by the Eukaryotic Elongation Factor 2 Is Required for the Anxiolytic Effect of Oxytocin. BIOLOGICAL PSYCHIATRY, 85 (10). pp. 802-811. ISSN 0006-3223, 1873-2402
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SOCIAL FEAR; KINASE; RECEPTOR; PHOSPHORYLATION; ACTIVATION; ANXIETY; TRANSLATION; VASOPRESSIN; STRESS; CELLS; Anxiety; De novo protein synthesis; eEF2; NPY5R; Oxytocin; PVN |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2020 08:52 |
| Last Modified: | 08 Apr 2020 08:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27006 |
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