| First Author | Aguilar-Valles A | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 2459 |
| PubMed ID | 29941989 | Mgi Jnum | J:266400 |
| Mgi Id | MGI:6209225 | Doi | 10.1038/s41467-018-04883-5 |
| Citation | Aguilar-Valles A, et al. (2018) Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E. Nat Commun 9(1):2459 |
| abstractText | Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution in the pathophysiology of depressive disorders is not fully understood. We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic initiation factor 4E), in depression-like behavior in mice. Mice carrying a mutation in eIF4E for the MNK1/2 phosphorylation site (Ser209Ala, Eif4e ki/ki), the Mnk1/2 double knockout mice (Mnk1/2(-/-)), or mice treated with the MNK1/2 inhibitor, cercosporamide, displayed anxiety- and depression-like behaviors, impaired serotonin-induced excitatory synaptic activity in the prefrontal cortex, and diminished firing of the dorsal raphe neurons. In Eif4e ki/ki mice, brain IkappaBalpha, was decreased, while the NF-kappaB target, TNFalpha was elevated. TNFalpha inhibition in Eif4e ki/ki mice rescued, whereas TNFalpha administration to wild-type mice mimicked the depression-like behaviors and 5-HT synaptic deficits. We conclude that eIF4E phosphorylation modulates depression-like behavior through regulation of inflammatory responses. |
