Translational animal models for the studying of 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. Microbiota consist of all microorganisms that cohabit in different district of an organism and which establish a bidirectional communication through metabolite, hormones, and neurotransmitters, which on the whole is called the gut-brain axis. Microbiota alterations have been correlated with different neuropsychiatry disorders; however few studies investigate the influence of microbiota with PTSD onset. Here we proposed a novel arousal-based individual screening (AIS) model that recapitulate the main aspects necessary to obtain a preclinical model with a great translational value for the study of PTSD that include different molecular and behavioral aspects of pathology. The AIS model allows us to discriminate trauma-exposed mice in susceptible, with a long-lasting PTSD-like phenotype, and resilient, which exhibit a similar phenotype to control group. Through this model we investigated how microbiota alteration, induced by an acute stress, was correlated with PTSD-like phenotypes onset. We observed a different coping strategy to stress with different alterations in the microbiota composition in trauma-exposed mice, with a particular increase of bacteria involved in the production of harmful metabolites in susceptible mice. Further analysis showed alteration in the gut-brain and gut-metabolic modules in susceptible and resilient groups indicating a different gut-brain axis communication and consequently a different response to traumatic stress event.
I modelli preclinici per lo studio del disturbo da stress post-traumatico (PTSD) sono fondamentali per comprendere i meccanismi neurobiologici di questa patologia. Questi, per poter essere validati, dovrebbero includere diversi criteri, tra le quali un fenotipo PTSD-like persistente dopo l’esposizione ad un evento traumatico, distinzione tra suscettibilità e resilienza al trauma e una validità predittiva. Il microbiota comprende tutti i microorganismi che vivono nei vari distretti di un organismo con il quale stabiliscono una comunicazione bidirezionale attraverso la produzione di metaboliti, ormoni e neurotrasmettitori, che nel complesso viene chiamato gut-brain axis. Alterazioni del microbiota sono state correlate a differenti patologie neuropsichiatriche; tuttavia, pochi studi hanno ricercato una possibile correlazione tra alterazioni del microbiota e PTSD. In questo lavoro presentiamo un innovativo modello preclinico per lo studio del PTSD (arousal-based individual screening (AIS) model) capace di includere numerosi aspetti molecolari e comportamentali della patologia. L’AIS model ci ha permesso di discriminare i topi esposti al trauma in suscettibili, con un fenotipo PTSD-like persistente nel tempo, e resilienti, con un fenotipo simile al gruppo di controllo. Attraverso l’uso di questo modello abbiamo analizzato come le alterazioni nella composizione del microbiota, indotte da uno stress acuto, fossero correlate con il manifestarsi del fenotipo PTSD-like. Abbiamo osservato, inoltre, una differente risposta allo stress con alterazioni nella composizione del microbiota nei suscettibili, caratterizzato da un aumento dei batteri coinvolti nella produzione di metaboliti dannosi. Ulteriori analisi hanno messo in evidenza dei cambiamenti nei gut-brain e gut-metabolic modules nei topi esposti allo stress, indicando una differente comunicazione tra gut e brain e, conseguentemente, una differente risposta all’evento traumatico.
SUSCETTIBILITA' ALLO STRESS E MICROBIOTA: NUOVE EVIDENZE PER COMPRENDERE LA PATOFISIOLOGIA DEL PTSD / Laudani, Samuele. - (2022 Apr 11).
SUSCETTIBILITA' ALLO STRESS E MICROBIOTA: NUOVE EVIDENZE PER COMPRENDERE LA PATOFISIOLOGIA DEL PTSD
LAUDANI, SAMUELE
2022-04-11
Abstract
Translational animal models for the studying of 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. Microbiota consist of all microorganisms that cohabit in different district of an organism and which establish a bidirectional communication through metabolite, hormones, and neurotransmitters, which on the whole is called the gut-brain axis. Microbiota alterations have been correlated with different neuropsychiatry disorders; however few studies investigate the influence of microbiota with PTSD onset. Here we proposed a novel arousal-based individual screening (AIS) model that recapitulate the main aspects necessary to obtain a preclinical model with a great translational value for the study of PTSD that include different molecular and behavioral aspects of pathology. The AIS model allows us to discriminate trauma-exposed mice in susceptible, with a long-lasting PTSD-like phenotype, and resilient, which exhibit a similar phenotype to control group. Through this model we investigated how microbiota alteration, induced by an acute stress, was correlated with PTSD-like phenotypes onset. We observed a different coping strategy to stress with different alterations in the microbiota composition in trauma-exposed mice, with a particular increase of bacteria involved in the production of harmful metabolites in susceptible mice. Further analysis showed alteration in the gut-brain and gut-metabolic modules in susceptible and resilient groups indicating a different gut-brain axis communication and consequently a different response to traumatic stress event.File | Dimensione | Formato | |
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