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A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice.
Torrisi, Sebastiano A; Lavanco, Gianluca; Maurel, Oriana M; Gulisano, Walter; Laudani, Samuele; Geraci, Federica; Grasso, Margherita; Barbagallo, Cristina; Caraci, Filippo; Bucolo, Claudio; Ragusa, Marco; Papaleo, Francesco; Campolongo, Patrizia; Puzzo, Daniela; Drago, Filippo; Salomone, Salvatore; Leggio, Gian Marco.
Afiliação
  • Torrisi SA; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Lavanco G; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Maurel OM; INSERM, U1215 Neurocentre Magendie and University of Bordeaux, Bordeaux, France.
  • Gulisano W; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Laudani S; Research Group "Neuronal Plasticity", Max Planck Institute of Psychiatry, Munich, Germany.
  • Geraci F; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Grasso M; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Barbagallo C; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Caraci F; Oasi Research Institute-IRCCS, Troina, Italy.
  • Bucolo C; Department of Drug Sciences, University of Catania, Catania, Italy.
  • Ragusa M; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Papaleo F; Oasi Research Institute-IRCCS, Troina, Italy.
  • Campolongo P; Department of Drug Sciences, University of Catania, Catania, Italy.
  • Puzzo D; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Drago F; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
  • Salomone S; Oasi Research Institute-IRCCS, Troina, Italy.
  • Leggio GM; Genetics of Cognition Laboratory, Neuroscience area, Istituto Italiano di Tecnologia, Genova, Italy.
Neurobiol Stress ; 14: 100286, 2021 May.
Article em En | MEDLINE | ID: mdl-33392367
ABSTRACT
Translational animal models for studying post-traumatic stress disorder (PTSD) are valuable for elucidating the poorly understood neurobiology of this neuropsychiatric disorder. These models should encompass crucial features, including persistence of PTSD-like phenotypes triggered after exposure to a single traumatic event, trauma susceptibility/resilience and predictive validity. Here we propose a novel arousal-based individual screening (AIS) model that recapitulates all these features. The AIS model was designed by coupling the traumatization (24 h restraint) of C57BL/6 J mice with a novel individual screening. This screening consists of z-normalization of post-trauma changes in startle reactivity, which is a measure of arousal depending on neural circuits conserved across mammals. Through the AIS model, we identified susceptible mice showing long-lasting hyperarousal (up to 56 days post-trauma), and resilient mice showing normal arousal. Susceptible mice further showed persistent PTSD-like phenotypes including exaggerated fear reactivity and avoidance of trauma-related cue (up to 75 days post-trauma), increased avoidance-like behavior and social/cognitive impairment. Conversely, resilient mice adopted active coping strategies, behaving like control mice. We further uncovered novel transcriptional signatures driven by PTSD-related genes as well as dysfunction of hypothalamic-pituitary-adrenal axis, which corroborated the segregation in susceptible/resilient subpopulations obtained through the AIS model and correlated with trauma susceptibility/resilience. Impaired hippocampal synaptic plasticity was also observed in susceptible mice. Finally, chronic treatment with paroxetine ameliorated the PTSD-like phenotypes of susceptible mice. These findings indicate that the AIS model might be a new translational animal model for the study of crucial features of PTSD. It might shed light on the unclear PTSD neurobiology and identify new pharmacological targets for this difficult-to-treat disorder.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article