scholarly journals Microglial deletion and inhibition alleviate behavior of post-traumatic stress disorder in mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shuoshuo Li ◽  
Yajin Liao ◽  
Yuan Dong ◽  
Xiaoheng Li ◽  
Jun Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Microglial Activation ◽  
Stress Disorder ◽  
Critical Role ◽  
Post Traumatic Stress ◽  
Minocycline Treatment ◽  
Post Traumatic ◽  
Shock Exposure

Abstract Background Alteration of immune status in the central nervous system (CNS) has been implicated in the development of post-traumatic stress disorder (PTSD). However, the nature of overall changes in brain immunocyte landscape in PTSD condition remains unclear. Methods We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open-field test, and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single-cell mass cytometry. Microglia number and morphological changes in the hippocampus, prefrontal cortex, and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shocks exposure was performed to study the role of microglia in PTSD development and progress. Results We found microglia are the major brain immune cells that respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of the PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear. Conclusion Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.

scholarly journals Microglial Deletion and Inhibition Alleviate Behavior of Post-Traumatic Stress Disorder in Mice

2020 ◽  
Author(s):  
Shuoshuo Li ◽  
Yajin Liao ◽  
Yuan Dong ◽  
Xiaoheng Li ◽  
Jun Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Microglial Activation ◽  
Stress Disorder ◽  
Critical Role ◽  
Post Traumatic Stress ◽  
Minocycline Treatment ◽  
Post Traumatic ◽  
Shock Exposure

Abstract Background: Alteration of immune status in the central nervous system (CNS) has been implicated in the development of Post-Traumatic Stress Disorder (PTSD). However, the nature of overall changes in brain immunocyte landscape in PTSD condition remains unclear. Methods: We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open filed test and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single cell mass cytometry. Microglia number and morphological changes in hippocampus, prefrontal cortex and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure were performed to study the role of microglia in the PTSD development and progress. Results: We found microglia are the major brain immune cells respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear. Conclusion: Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.

scholarly journals Gene Expression Differences Between Young Adults Based on Trauma History and Post-traumatic Stress Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaitlin E. Bountress ◽  
Vladimir Vladimirov ◽  
Gowon McMichael ◽  
Z. Nathan Taylor ◽  
Gary Hardiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Gene Network ◽  
Stress Disorder ◽  
Trauma Exposure ◽  
Differentially Expressed ◽  
Post Traumatic Stress ◽  
Network Analyses ◽  
Post Traumatic

Background: The purpose of this study was to identify gene expression differences associated with post-traumatic stress disorder (PTSD) and trauma exposure (TE) in a three-group study design comprised of those with and without trauma exposure and PTSD.Methods: We conducted gene expression and gene network analyses in a sample (n = 45) composed of female subjects of European Ancestry (EA) with PTSD, TE without PTSD, and controls.Results: We identified 283 genes differentially expressed between PTSD-TE groups. In an independent sample of Veterans (n = 78) a small minority of these genes were also differentially expressed. We identified 7 gene network modules significantly associated with PTSD and TE (Bonferroni corrected p ≤ 0.05), which at a false discovery rate (FDR) of q ≤ 0.2, were significantly enriched for biological pathways involved in focal adhesion, neuroactive ligand receptor interaction, and immune related processes among others.Conclusions: This study uses gene network analyses to identify significant gene modules associated with PTSD, TE, and controls. On an individual gene level, we identified a large number of differentially expressed genes between PTSD-TE groups, a minority of which were also differentially expressed in the independent sample. We also demonstrate a lack of network module preservation between PTSD and TE, suggesting that the molecular signature of PTSD and trauma are likely independent of each other. Our results provide a basis for the identification of likely disease pathways and biomarkers involved in the etiology of PTSD.

scholarly journals Transcriptional Control of Monocyte Gene Expression in Post-Traumatic Stress Disorder

2011 ◽  
Vol 30 (2-3) ◽  
pp. 123-132 ◽  
Author(s):  
Aoife O’Donovan ◽  
Bing Sun ◽  
Steve Cole ◽  
Hans Rempel ◽  
Maryann Lenoci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Transcriptional Control ◽  
Target Genes ◽  
Stress Disorder ◽  
Post Traumatic Stress ◽  
Down Regulation ◽  
Increased Risk ◽  
Post Traumatic

Post-traumatic stress disorder (PTSD) confers an increased risk for disorders with an inflammatory etiology. PTSD-related dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis and associated alterations in inflammatory activity may contribute to this increased risk. However, little is known about convergent SNS, HPA and inflammatory signaling at the level of the immune cell transcriptome in PTSD. To explore such signaling, we examined the prevalence of specific transcription factor binding motifs in the promoter regions of differentially expressed genes in monocytes from individuals with PTSD and matched controls. Participants included 49 men (24 PTSD+ and 25 trauma-exposed controls) and 18 women (10 PTSD+ and 8 controls). Men with PTSD showed up-regulation of target genes for the NF-κB/Rel family of transcription factors, which convey inflammatory signals, up-regulation of target genes for CREB/ATF transcription factors, which convey adrenergic signals from the SNS, and down-regulation of target genes for the glucocorticoid receptor, which conveys glucocorticoid signals from the HPA axis. Women with PTSD also showed significant up-regulation of target genes for NF-κB and non-significant down-regulation of target genes for GR, but significant down-regulation of target genes for CREB/ATF. Altered transcriptional control of monocyte gene expression could contribute to exaggerated inflammatory activity in PTSD.

Epigenetic Effects of PTSD Remediation in Veterans Using Clinical Emotional Freedom Techniques: A Randomized Controlled Pilot Study

2016 ◽  
Vol 32 (1) ◽  
pp. 112-122 ◽  
Author(s):  
Dawson Church ◽  
Garret Yount ◽  
Kenneth Rachlin ◽  
Louis Fox ◽  
Jerrod Nelms
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Intervention Period ◽  
Post Traumatic Stress ◽  
Ptsd Treatment ◽  
Epigenetic Effects ◽  
Post Traumatic

Purpose: To assess the feasibility of measuring changes in gene expression associated with post-traumatic stress disorder (PTSD) treatment using emotional freedom techniques (EFT). Design: Participants were randomized into an EFT group receiving EFT and treatment as usual (TAU) throughout a 10-week intervention period and a group receiving only TAU during the intervention period and then receiving EFT. Setting: A community clinic and a research institute in California. Participants: Sixteen veterans with clinical levels of PTSD symptoms. Intervention: Ten hour-long sessions of EFT. Measures: Messenger RNA levels for a focused panel of 93 genes related to PTSD. The Symptom Assessment 45 questionnaire, Hospital Anxiety and Depression Scale, Insomnia Severity Scale, SF-12v2 for physical impairments, and Rivermead Postconcussion Symptoms Questionnaire. Analysis: Pre-, posttreatment, and follow-up mean scores on questionnaires were assessed using repeated measures 1-way analysis of variance. A Student t test and post hoc analyses were performed on gene expression data. Results: Post-traumatic stress disorder symptoms declined significantly in the EFT group (−53%, P < .0001). Participants maintained their gains on follow-up. Significant differential expression of 6 genes was found ( P < .05) when comparing the expression levels before and after the intervention period in participants receiving EFT. Conclusion: Study results identify candidate gene expression correlates of successful PTSD treatment, providing guidelines for the design of further studies aimed at exploring the epigenetic effects of EFT.

scholarly journals Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study

2015 ◽  
Vol 51 ◽  
pp. 472-494 ◽  
Author(s):  
Daniel S. Tylee ◽  
Sharon D. Chandler ◽  
Caroline M. Nievergelt ◽  
Xiaohua Liu ◽  
Joel Pazol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pilot Study ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Post Traumatic Stress ◽  
Post Traumatic

scholarly journals Time‐course analysis of gene expression in a mouse model simulating aspects of human post‐traumatic stress disorder (776.7)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
seid Muhie ◽  
Seshamalini Srinivasan ◽  
Aarti Gautam ◽  
Nabarun Chakraborty ◽  
Rasha Hammamieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Time Course ◽  
Stress Disorder ◽  
Post Traumatic Stress ◽  
Post Traumatic

scholarly journals DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Aliza P. Wingo ◽  
Lynn M. Almli ◽  
Jennifer S. Stevens ◽  
Torsten Klengel ◽  
Monica Uddin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Stress Disorder ◽  
Mirna Regulation ◽  
Post Traumatic Stress ◽  
Comorbid Depression ◽  
Genome Wide ◽  
Post Traumatic

Abstract DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.

scholarly journals A review of epigenetic contributions to post-traumatic stress disorder

2019 ◽  
Vol 21 (4) ◽  
pp. 417-428 ◽  
Keyword(s):  
Gene Expression ◽  
Genetic Code ◽  
Epigenetic Regulation ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Regulation Of Gene Expression ◽  
Direct Result ◽  
Post Traumatic Stress ◽  
Post Traumatic

Post-traumatic stress disorder (PTSD) is a syndrome which serves as a classic example of psychiatric disorders that result from the intersection of nature and nurture, or gene and environment. By definition, PTSD requires the experience of a traumatic exposure, and yet data suggest that the risk for PTSD in the aftermath of trauma also has a heritable (genetic) component. Thus, PTSD appears to require both a biological (genetic) predisposition that differentially alters how the individual responds to or recovers from trauma exposure. Epigenetics is defined as the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself, and more recently it has come to refer to direct alteration of DNA regulation, but without altering the primary sequence of DNA, or the genetic code. With regards to PTSD, epigenetics provides one way for environmental exposure to be “written” upon the genome, as a direct result of gene and environment (trauma) interactions. This review provides an overview of the main currently understood types of epigenetic regulation, including DNA methylation, histone regulation of chromatin, and noncoding RNA regulation of gene expression. Furthermore, we examine recent literature related to how these methods of epigenetic regulation may be involved in differential risk and resilience for PTSD in the aftermath of trauma.

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