title: Effects of Forced Swimming Stress on ERK and Histone H3 Phosphorylation in Limbic Areas of Roman High- and Low-Avoidance Rats.
abstract: Stressful events evoke molecular adaptations of neural circuits through chromatin remodeling and regulation of gene expression. However, the identity of the molecular pathways activated by stress in experimental models of depression is not fully understood. We investigated the effect of acute forced swimming (FS) on the phosphorylation of the extracellular signal-regulated kinase (ERK)1/2 (pERK) and histone H3 (pH3) in limbic brain areas of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression-like behavior. We demonstrate that FS markedly increased the density of pERK-positive neurons in the infralimbic (ILCx) and the prelimbic area (PrLCx) of the prefrontal cortex (PFCx), the nucleus accumbens, and the dorsal blade of the hippocampal dentate gyrus to the same extent in RLA and RHA rats. In addition, FS induced a significant increase in the intensity of pERK immunoreactivity (IR) in neurons of the PFCx in both rat lines. However, RHA rats showed stronger pERK-IR than RLA rats in the ILCx both under basal and stressed conditions. Moreover, the density of pH3-positive neurons was equally increased by FS in the PFCx of both rat lines. Interestingly, pH3-IR was higher in RHA than RLA rats in PrLCx and ILCx, either under basal conditions or upon FS. Finally, colocalization analysis showed that in the PFCx of both rat lines, almost all pERK-positive cells express pH3, whereas only 50% of the pH3-positive neurons is also pERK-positive. Moreover, FS increased the percentage of neurons that express exclusively pH3, but reduced the percentage of cells expressing exclusively pERK. These results suggest that (i) the distinctive patterns of FS-induced ERK and H3 phosphorylation in the PFCx of RHA and RLA rats may represent molecular signatures of the behavioural traits that distinguish the two lines and (ii) FS-induced H3 phosphorylation is, at least in part, ERK-independent.
authors.affiliation: Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Noemi
authors.initials: N
authors.lastname: Morello
authors.affiliation: Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Plicato
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Piludu
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Monserrato (CA), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Poddighe
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Monserrato (CA), Italy.
authors.forename: Maria Pina
authors.initials: MP
authors.lastname: Serra
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Monserrato (CA), Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Quartu
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Giuseppa
authors.initials: MG
authors.lastname: Corda
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Giorgi
authors.affiliation: Department of Neuroscience, University of Turin, Turin, Italy.|National Institute of Neuroscience-Italy, Turin, Italy.
authors.forename: Maurizio
authors.identifier: http://orcid.org/0000-0003-1323-4060
authors.initials: M
authors.lastname: Giustetto
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008032:Limbic System / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D013045:Species Specificity; D013312:Stress, Physiological; D013550:Swimming
chemical_list: D006657:Histones; D048049:Extracellular Signal-Regulated MAP Kinases