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

• Verfasst von: Cosentino, Livia [VerfasserIn]
• Verfasst von: Vigli, Daniele [VerfasserIn]
• Verfasst von: Medici, Vanessa [VerfasserIn]
• Verfasst von: Flor, Herta [VerfasserIn]
• Verfasst von: Lucarelli, Marco [VerfasserIn]
• Verfasst von: Fuso, Andrea [VerfasserIn]
• Verfasst von: De Filippis, Bianca [VerfasserIn]
• Titel: Methyl-CpG binding protein 2 functional alterations provide vulnerability to develop behavioral and molecular features of post-traumatic stress disorder in male mice
• Verf.angabe: Livia Cosentino, Daniele Vigli, Vanessa Medici, Herta Flor, Marco Lucarelli, Andrea Fuso, Bianca De Filippis
• E-Jahr: 2019
• Jahr: 06 June 2019
• Umfang: 7 S.
• Fussnoten: Gesehen am 30.01.2020
• Titel Quelle: Enthalten in: Neuropharmacology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1970
• Jahr Quelle: 2019
• Band/Heft Quelle: 160(2019), Artikel-ID 107664, Seite 1-7
• ISSN Quelle: 1873-7064
• DOI: doi:10.1016/j.neuropharm.2019.06.003
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Avoidance
• Sach-SW: Epigenetics
• Sach-SW: MeCP2
• Sach-SW: Memory
• Sach-SW: PTSD
• Sach-SW: Susceptibility
• K10plus-PPN: 1688934049

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.