Post-traumatic stress disorder (PTSD) is a mental disorder characterized by symptoms of persistent anxiety arising after exposure to traumatic events. Stress susceptibility due to a complex interplay between genetic and environmental factors plays a major role in the disease etiology, although biological underpinnings have not been clarified. We hypothesized that aberrant functionality of the methyl-CpG binding protein 2 (MECP2), a master regulator of experience-dependent epigenetic programming, confers susceptibility to develop PTSD-like symptomatology in the aftermath of traumatic events. Transgenic male mice expressing a truncated form of MeCP2 protein (MeCP2-308) were exposed at adulthood to a trauma in the form of high-intensity footshocks. The presence and duration of PTSD-like symptoms were assessed and compared to those of trauma-exposed wild type littermates and MeCP2-308 mice subjected to a mild stressor. The effects of fluoxetine, a prime pharmacological PTSD treatment, on PTSD-like symptomatology were also explored. Trauma-exposed MeCP2-308 mice showed long-lasting hyperresponsiveness to both correct and incorrect predictors of the trauma and persistent increased avoidance of trauma-related cues. Traumatized MeCP2-308 mice also displayed abnormal post-traumatic plasma levels of the stress hormone corticosterone and altered peripheral gene expression mirroring that of PTSD patients. Fluoxetine improved PTSD-like symptoms in trauma-exposed MeCP2-308 mice. These findings provide evidence that MeCP2 dysfunction results in increased susceptibility to develop PTSD-like symptoms after trauma exposure, and identify trauma-exposed MeCP2-308 mice as a new tool to investigate the underpinnings of PTSD vulnerability.

Methyl-CpG binding protein 2 functional alterations provide vulnerability to develop behavioral and molecular features of post-traumatic stress disorder in male mice / Cosentino, Livia; Vigli, Daniele; Medici, Vanessa; Flor, Herta; Lucarelli, Marco; Fuso, Andrea; De Filippis, Bianca. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - 160:(2019), p. 107664. [10.1016/j.neuropharm.2019.06.003]

Methyl-CpG binding protein 2 functional alterations provide vulnerability to develop behavioral and molecular features of post-traumatic stress disorder in male mice

Cosentino, Livia
Primo
;
Vigli, Daniele;Lucarelli, Marco;Fuso, Andrea;
2019

Abstract

Post-traumatic stress disorder (PTSD) is a mental disorder characterized by symptoms of persistent anxiety arising after exposure to traumatic events. Stress susceptibility due to a complex interplay between genetic and environmental factors plays a major role in the disease etiology, although biological underpinnings have not been clarified. We hypothesized that aberrant functionality of the methyl-CpG binding protein 2 (MECP2), a master regulator of experience-dependent epigenetic programming, confers susceptibility to develop PTSD-like symptomatology in the aftermath of traumatic events. Transgenic male mice expressing a truncated form of MeCP2 protein (MeCP2-308) were exposed at adulthood to a trauma in the form of high-intensity footshocks. The presence and duration of PTSD-like symptoms were assessed and compared to those of trauma-exposed wild type littermates and MeCP2-308 mice subjected to a mild stressor. The effects of fluoxetine, a prime pharmacological PTSD treatment, on PTSD-like symptomatology were also explored. Trauma-exposed MeCP2-308 mice showed long-lasting hyperresponsiveness to both correct and incorrect predictors of the trauma and persistent increased avoidance of trauma-related cues. Traumatized MeCP2-308 mice also displayed abnormal post-traumatic plasma levels of the stress hormone corticosterone and altered peripheral gene expression mirroring that of PTSD patients. Fluoxetine improved PTSD-like symptoms in trauma-exposed MeCP2-308 mice. These findings provide evidence that MeCP2 dysfunction results in increased susceptibility to develop PTSD-like symptoms after trauma exposure, and identify trauma-exposed MeCP2-308 mice as a new tool to investigate the underpinnings of PTSD vulnerability.
2019
avoidance; epigenetics; MeCP2; memory; PTSD; Susceptibility
01 Pubblicazione su rivista::01a Articolo in rivista
Methyl-CpG binding protein 2 functional alterations provide vulnerability to develop behavioral and molecular features of post-traumatic stress disorder in male mice / Cosentino, Livia; Vigli, Daniele; Medici, Vanessa; Flor, Herta; Lucarelli, Marco; Fuso, Andrea; De Filippis, Bianca. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - 160:(2019), p. 107664. [10.1016/j.neuropharm.2019.06.003]
File allegati a questo prodotto
File Dimensione Formato  
Cosentino_Methyl-CpG_2019.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 3.67 MB
Formato Adobe PDF
3.67 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1282147
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 10
social impact