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Cited by 19Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

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

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Morello, Noemi, Plicato, Ornella, Piludu, Maria Antonietta, Poddighe, Laura, Serra, Maria Pina, Quartu, Marina, Corda, Maria Giuseppa, Giorgi, Osvaldo +1 more·2017·PLOS ONE
DOI 10.1371/journal.pone.0170093PMC PMC5249133
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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.

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  • Several uncommon histone modifications, such as histone crotonylation, histone phosphorylation, and histone β-hydroxybutyrylation, are involved in the pathophysiology of MDD.

    “Several uncommon histone modifications, such as histone crotonylation, histone phosphorylation, and histone β-hydroxybutyrylation, are shown to be involved in the pathophysiology of MDD.176–178”

    From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [178]

    The Discussion reports differences in histone H3 phosphorylation between rat lines susceptible or resistant to depression-like behavior and suggests that histone modifications may contribute to their different stress responses. This supports a possible role for phosphorylation in an animal model, but does not establish its involvement in human MDD. The paper does not address crotonylation or β-hydroxybutyrylation; the other citations in the citing sentence may be intended to support those modifications. (LLM, conf=0.87)

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  • Rats exposed to forced swimming stress showed an increase in H3 phosphorylation in the infralimbic and prelimbic areas of the prefrontal cortex.

    “Rats exposed to forced swimming stress showed an increase in H3 phosphorylation in the infralimbic (ILCx) and prelimbic area (PrLCx) of the prefrontal cortex.187”

    From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [187]

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Authors
Morello, N., Plicato, O., Piludu, M. A., Poddighe, L., Serra, M. P., Quartu, M., Corda, M. G., Giorgi, O., & Giustetto, M.
Affiliations
  • University of Turin (IT)
  • University of Cagliari (IT)
Corresponding author
  • Morello, Noemi
  • Plicato, Ornella
  • Piludu, Maria Antonietta
  • Poddighe, Laura
  • Serra, Maria Pina
  • Quartu, Marina
  • Corda, Maria Giuseppa
  • Giorgi, Osvaldo
  • Giustetto, Maurizio
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-01-20
Volume
12
Issue
1
Pages
e0170093
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0170093
PMC
PMC5249133
OpenAlex
W2574059047
Cited by
19
References
35
Citations by year
2026: 1 · 2025: 2 · 2023: 1 · 2021: 7 · 2020: 2 · 2018: 3 · 2017: 3
FWCI
1.19
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion, cc-by)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, public-domain)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • ARS (Autonomous Region of Sardinia) (L.R. 7/2007 n. CRP-59842)
  • Università degli Studi di Torino (811M33N)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
forced swim stress, ERK1/2 phosphorylation, histone H3 phosphorylation, stress-induced depression, Roman high-avoidance rats, Roman low-avoidance rats, prefrontal cortex, infralimbic cortex, prelimbic cortex, nucleus accumbens, dentate gyrus, chromatin remodeling, gene expression regulation, behavioral characteristics
MeSH terms
Animals, Avoidance Learning, Enzyme Activation, Histones, Limbic System, Male, Phosphorylation, Species Specificity, Stress, Physiological, Swimming, Extracellular Signal-Regulated MAP Kinases, Rats

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