Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E

• DOI: 10.1038/s41467-018-04883-5
• Publication Date: 2018-06-19T10:49:48Z
• Authors: Argel Aguilar-Valles; Nabila Haji; Danilo De Gregorio; Edna Matta-Camacho; Mohammad J. Eslam...; Jelena Popic; Vijendra Sharma; Ruifeng Cao; Christoph Rummel; Arnaud Tanti; Shane Wiebe; Nicolas Nuñez; Stefano Comai; Robert Nadon; Giamal Luheshi; Naguib Mechawar; Gustavo Turecki; Jean-Claude Lacaille; Gabriella Gobbi; Nahum Sonenberg
• Keywords: EIF4E; Eukaryotic initiation factor

Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution the pathophysiology depressive disorders is not fully understood. We investigated involvement MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 2) their target, eIF4E (eukaryotic initiation factor 4E), depression-like behavior mice. Mice carrying mutation for phosphorylation site (Ser209Ala, Eif4e ki/ki), Mnk1/2 double knockout mice (Mnk1/2-/-), or treated with inhibitor, cercosporamide, displayed anxiety- behaviors, impaired serotonin-induced excitatory synaptic activity prefrontal cortex, diminished firing dorsal raphe neurons. In ki/ki mice, brain IκBα, was decreased, while NF-κB TNFα elevated. inhibition rescued, whereas administration to wild-type mimicked behaviors 5-HT deficits. conclude that modulates through regulation inflammatory responses.