Methyl-CpG binding protein 2 functional alterations provide vulnerability to develop behavioral and molecular features of post-traumatic stress disorder in male mice
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 biolo...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
06 June 2019
|
| In: |
Neuropharmacology
Year: 2019, Volume: 160, Pages: 1-7 |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/j.neuropharm.2019.06.003 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.neuropharm.2019.06.003 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0028390819302102 
|
| Author Notes: | Livia Cosentino, Daniele Vigli, Vanessa Medici, Herta Flor, Marco Lucarelli, Andrea Fuso, Bianca De Filippis |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 30.01.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/j.neuropharm.2019.06.003 |