title: Long-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2-MSK1-Elk-1 signaling.
abstract: Stressful events are known to have a long-term impact on future behavioral stress responses. Previous studies suggested that both glucocorticoid hormones and glutamate acting via glucocorticoid receptors (GRs) and N-methyl D-aspartate (NMDA) receptors, respectively, are of critical importance for the consolidation of these long-lasting behavioral responses at the dentate gyrus, the gateway of the hippocampal formation. We found that an acute psychologically stressful event resulted in ERK1/2 phosphorylation (pERK1/2), which within 15 min led to the activation of the nuclear kinases MSK1 and Elk-1 in granule neurons of the dentate gyrus. Next, MSK1 and Elk-1 activation evoked serine-10 phosphorylation and lysine-14 acetylation in histone H3, resulting in the induction of the neuroplasticity-associated immediate-early genes c-Fos and Egr-1 in these neurons. The pERK1/2-mediated activation of MSK1 and Elk-1 required a rapid protein-protein interaction between pERK1/2 and activated GRs. This is a unique nongenomic mechanism of glucocorticoid hormone action in dentate gyrus granule neurons on long-lasting behavioral responses to stress involving direct cross-talk of GRs with ERK1/2-MSK1-Elk-1 signaling to the nucleus.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom.
authors.forename: María
authors.initials: M
authors.lastname: Gutièrrez-Mecinas
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Trollope
authors.forename: Andrew
authors.initials: A
authors.lastname: Collins
authors.forename: Hazel
authors.initials: H
authors.lastname: Morfett
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Hesketh
authors.forename: Flavie
authors.initials: F
authors.lastname: Kersanté
authors.forename: Johannes M H M
authors.initials: JM
authors.lastname: Reul
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D018891:Dentate Gyrus; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
chemical_list: C494114:Elk1 protein, rat; D011965:Receptors, Glucocorticoid; D050807:ets-Domain Protein Elk-1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048052:Mitogen-Activated Protein Kinase 3