Effects of Forced Swimming Stress on ERK and Histone H3 Phosphorylation in Limbic Areas of Roman High- and Low-Avoidance Rats

• DOI: 10.1371/journal.pone.0170093
• Publication Date: 2017-01-20T19:29:22Z
• Authors: Noemi Morello; Ornella Plicato; Maria Antonietta ...; Laura Poddighe; Maria Pina Serra; Marina Quartu; Maria Giuseppa Corda; Osvaldo Giorgi; Maurizio Giustetto
• Keywords: Male; Science; Q; R; Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); Rats; Enzyme Activation; Histones; 03 medical and health sciences; 0302 clinical medicine; Species Specificity; Stress, Physiological; Avoidance Learning; Limbic System; Medicine; Animals; Forced swim test; Depression; Roman rats; Limbic brain areas; ERK; pERK; Histone H3; Phosphorylation; Extracellular Signal-Regulated MAP Kinases; Swimming; Research Article

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.