A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice.

Autor:	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.; INSERM, U1215 Neurocentre Magendie and University of Bordeaux, Bordeaux, France., Maurel OM; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.; Research Group 'Neuronal Plasticity', Max Planck Institute of Psychiatry, Munich, Germany., Gulisano W; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Laudani S; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Geraci F; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Grasso M; Oasi Research Institute-IRCCS, Troina, Italy.; Department of Drug 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.; Department of Drug Sciences, University of Catania, Catania, Italy., Bucolo C; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Ragusa M; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.; Oasi Research Institute-IRCCS, Troina, Italy., Papaleo F; Genetics of Cognition Laboratory, Neuroscience area, Istituto Italiano di Tecnologia, Genova, Italy., Campolongo P; Department of Physiology and Pharmacology 'Vittorio Erspamer', Sapienza University of Rome, Rome, Italy.; Neurobiology of Behavior Laboratory, Santa Lucia Foundation, Rome, 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; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Leggio GM; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Jazyk:	angličtina
Zdroj:	Neurobiology of stress [Neurobiol Stress] 2020 Dec 24; Vol. 14, pp. 100286. Date of Electronic Publication: 2020 Dec 24 (Print Publication: 2021).
DOI:	10.1016/j.ynstr.2020.100286
Abstrakt:	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. (© 2020 The Authors.)
Databáze:	MEDLINE
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