About this item:

45 Views | 29 Downloads

Author Notes:

Corresponding author: Raül Andero, PhD, Institut de Neurociencies, Unitat de Psicobiologia (Facultat de Psicologia), Universitat Autonoma de Barcelona, CIBERSAM, Contact, Office M1-141, UAB Campus, Bellaterra, 08193, Barcelona, Spain, raul.andero@uab.cat, Ph +34 93 581 33 42, Fax +34 93 581 41 52.

We would like to thank Dr. Greg Gibson (Georgia Tech, USA) for his comments on this paper and data on Figure 3B.

We are thankful to Dr. Antonio Armario and Dr. Roser Nadal for support on this work.

We would also like to thank the staff and participants of the Grady Trauma Project for their contributions to this important work.

All authors report no biomedical financial interests or potential conflicts of interest.

Subjects:

Research Funding:

KJR received support from the Howard Hughes Medical Institute, RA and KJR were supported by R21MH101492-01, KJR by R01MH071537 and R01MH096764, and RA by a NARSAD Young Investigator Grant (22434), Ramon y Cajal RYC-2014-15784 MINECO and SAF2016-76565-R MINECO and FEDER.

APW was supported by the Department of Veterans Affairs Career Development Award IK2CX000601.

TJ has support from NARSAD and R01MH100122.

The UAB Animal Facility received funding from 2015 FEDER7S-20IU16-001945.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • Anxiety
  • CAMK2
  • Depression
  • PPM1F
  • PTSD
  • Stress
  • PROTEIN-KINASE-II
  • CORONARY-HEART-DISEASE
  • POSTTRAUMATIC-STRESS
  • PREFRONTAL CORTEX
  • DISORDER SYMPTOMS
  • 5-HT1A RECEPTORS
  • EXPOSURE
  • CAMKII
  • PHOSPHATASE
  • AMYGDALA

Expression of the PPM1F Gene Is Regulated by Stress and Associated With Anxiety and Depression

Tools:

Journal Title:

Biological Psychiatry

Volume:

Volume 83, Number 3

Publisher:

, Pages 284-295

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background Molecular mechanisms underlying psychological sequelae of exposure to stressful experiences, such as posttraumatic stress disorder (PTSD) and depression, are not well understood. Methods Using convergent evidence from animal and human transcriptomic and genomic studies, we aimed to identify genetic mechanisms underlying depression and anxiety after traumatic experiences. Results From a transcriptome-wide analysis in mice, we found the Ppm1f gene to be differentially expressed in the amygdala and medial prefrontal cortex (mPFC) a week after immobilization stress. Next, we found that PPM1F messenger RNA levels in human blood were downregulated in cases with symptoms of comorbid PTSD and depression and consistently in cases with anxiety symptoms in a separate human dataset. Furthermore, we showed that a genetic variant of PPM1F, rs17759843, was associated with comorbid PTSD and depression and with PPM1F expression in both human brain and blood. Given prior reported mechanistic links between PPM1F and CAMK2 (CAMKII), we examined blood messenger RNA level of CAMK2G in humans and found it to be lower in cases with comorbid PTSD and depression. We also found that PPM1F protein levels and colocalization with CAMK2G were altered in amygdala and mPFC of male mice. Additionally, we found that a systemic dose of corticosterone blocked the depressive-like phenotype elicited by stress in female mice. Lastly, corticosterone rescued the anxiety-like phenotype and messenger RNA levels of Ppm1f in amygdala and mPFC in male mice and in mPFC of female mice. Conclusions Taken together, our data suggest a mechanistic pathway involving PPM1F and CAMK2G in stress- and trauma-related manifestation of anxiety and depression across species.

Copyright information:

© 2017 Society of Biological Psychiatry

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote