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A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice
| dc.rights.license | open | en_US |
| dc.contributor.author | TORRISI, Sebastiano A. | |
| hal.structure.identifier | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB] | |
| dc.contributor.author | LAVANCO, Gianluca | |
| dc.contributor.author | MAUREL, Oriana M. | |
| dc.contributor.author | GULISANO, Walter | |
| dc.contributor.author | LAUDANI, Samuele | |
| dc.contributor.author | GERACI, Federica | |
| dc.contributor.author | GRASSO, Margherita | |
| dc.contributor.author | BARBAGALLO, Cristina | |
| dc.contributor.author | CARACI, Filippo | |
| dc.contributor.author | BUCOLO, Claudio | |
| dc.contributor.author | RAGUSA, Marco | |
| dc.contributor.author | PAPALEO, Francesco | |
| dc.contributor.author | CAMPOLONGO, Patrizia | |
| dc.contributor.author | PUZZO, Daniela | |
| dc.contributor.author | DRAGO, Filippo | |
| dc.contributor.author | SALOMONE, Salvatore | |
| dc.contributor.author | LEGGIO, Gian Marco | |
| dc.date.accessioned | 2022-03-04T10:57:38Z | |
| dc.date.available | 2022-03-04T10:57:38Z | |
| dc.date.issued | 2021-05 | |
| dc.identifier.issn | 2352-2895 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/128827 | |
| dc.description.abstractEn | 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. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject.en | Animal model | |
| dc.subject.en | Fear conditioning | |
| dc.subject.en | Resilience | |
| dc.subject.en | Stress | |
| dc.subject.en | Susceptibility | |
| dc.subject.en | Z-score | |
| dc.title.en | A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice | |
| dc.title.alternative | Neurobiol Stress | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.ynstr.2020.100286 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 33392367 | en_US |
| bordeaux.journal | Neurobiology of Stress | en_US |
| bordeaux.volume | 14 | en_US |
| bordeaux.hal.laboratories | Neurocentre Magendie - UMR-S 1215 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Università di Catania | en_US |
| bordeaux.identifier.funderID | Ministero dell’Istruzione, dell’Università e della Ricerca | en_US |
| hal.identifier | hal-03597540 | |
| hal.version | 1 | |
| hal.date.transferred | 2022-03-04T10:57:42Z | |
| hal.export | true | |
| dc.rights.cc | CC BY-NC-ND | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Neurobiology%20of%20Stress&rft.date=2021-05&rft.volume=14&rft.eissn=2352-2895&rft.issn=2352-2895&rft.au=TORRISI,%20Sebastiano%20A.&LAVANCO,%20Gianluca&MAUREL,%20Oriana%20M.&GULISANO,%20Walter&LAUDANI,%20Samuele&rft.genre=article |
