Gene and stress history interplay in emergence of PTSD-like features

Chakraborty, Nabarun; Meyerhoff, James L.; Gautam, Aarti; Muhie, Seid; Jibitu, Meskerem; Lima, Thereza Christina Monteiro de; Hammamieh, Rasha; Jett, Marti

doi:10.1016/j.bbr.2015.05.038

Cited by 11 publications

(10 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Details about the mouse model and PTSD-related behavioral characterizations of the model have been reported earlier. 12 , 13 Briefly, naive C57BL/6 male mice (8–10 weeks old) were single-housed, and mice ( N =5 per group) were randomly assigned to aggressor-exposed (Agg-E) and cage-control (C-ctrl) groups for each time point. Each Agg-E mouse was kept in a mesh box inside the cage of a trained, highly aggressive, resident SJL mouse for 6 h/day for either 5 (T5) or 10 (T10) consecutive days.…”

Section: Methodsmentioning

confidence: 99%

“… 12 Such random exposure to a conspecific aggressor was found to elicit important behavioral features reported to occur in PTSD patients such as avoidance of trauma reminders (marked avoidance of aggressor barrier), jumping during handling (increased vigilance) or freezing (social withdrawal) and impaired cognition. 12 , 13 , 14 Using this model, we profiled transcriptome alterations in brain regions (hippocampus, amygdala, medial prefrontal cortex and hemibrain), blood and spleen as well as DNA methylome changes in the hemibrain at multiple time points.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder

et al. 2017

View full text Add to dashboard Cite

A social-stress mouse model was used to simulate features of post-traumatic stress disorder (PTSD). The model involved exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse for 5 or 10 consecutive days. Transcriptome changes in brain regions (hippocampus, amygdala, medial prefrontal cortex and hemibrain), blood and spleen as well as epigenome changes in the hemibrain were assayed after 1- and 10-day intervals following the 5-day trauma or after 1- and 42-day intervals following the 10-day trauma. Analyses of differentially expressed genes (common among brain, blood and spleen) and differentially methylated promoter regions revealed that neurogenesis and synaptic plasticity pathways were activated during the early responses but were inhibited after the later post-trauma intervals. However, inflammatory pathways were activated throughout the observation periods, except in the amygdala in which they were inhibited only at the later post-trauma intervals. Phenotypically, inhibition of neurogenesis was corroborated by impaired Y-maze behavioral responses. Sustained neuroinflammation appears to drive the development and maintenance of behavioral manifestations of PTSD, potentially via its inhibitory effect on neurogenesis and synaptic plasticity. By contrast, peripheral inflammation seems to be directly responsible for tissue damage underpinning somatic comorbid pathologies. Identification of overlapping, differentially regulated genes and pathways between blood and brain suggests that blood could be a useful and accessible brain surrogate specimen for clinical translation.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Animal models have also implicated alterations in the transcriptome of the amygdala in underlying neuronal plasticity (Ponomarev et al, 2010) and changes in hippocampal plasticity via proteomic alterations (Rao-Ruiz et al, 2015). Similar to the HPA axis dysregulation in PTSD, fear conditioning in rodents has been linked to prefrontal GR activity (Reis et al, 2015) and FKBP5 expression (Chakraborty et al, 2015). This same experimental paradigm has been used to assess the effects of corticosterone on contextual fear memory formation (reviewed in (Pecoraro et al, 2006)), and the findings have been equivocal.…”

Section: Delineating the Relationships: Insight From Animal Modelsmentioning

confidence: 99%

Posttraumatic stress disorder: A metabolic disorder in disguise?

Michopoulos

Vester

Neigh

2016

Experimental Neurology

104

103

View full text Add to dashboard Cite

Posttraumatic stress disorder (PTSD) is a heterogeneous psychiatric disorder that affects individuals exposed to trauma and is highly co-morbid with other adverse health outcomes, including cardiovascular disease and obesity. The unique pathophysiological feature of PTSD is the inability to inhibit fear responses, such that individuals suffering from PTSD re-experience traumatic memories and are unable to control psychophysiological responses to trauma-associated stimuli. However, underlying alterations in sympathetic nervous system activity, neuroendocrine systems, and metabolism associated with PTSD are similar to those present in traditional metabolic disorders, such as obesity and diabetes. The current review highlights existing clinical, translational, and preclinical data that support the notion that underneath the primary indication of impaired fear inhibition, PTSD is itself also a metabolic disorder and proposes altered function of inflammatory responses as a common underlying mechanism. The therapeutic implications of treating PTSD as a whole-body condition are significant, as targeting any underlying biological system whose activity is altered in both PTSD and metabolic disorders, (i.e. HPA axis, sympathetic nervous systems, inflammation) may elicit symptomatic relief in individuals suffering from these whole-body adverse outcomes.

show abstract

“…MAP6 is in the centre of the QTL confidence interval and mediates neuronal connectivity for axonal growth 52 . It has been linked with synaptic plasticity anomalies and has associations with schizophrenia through neuronal transport defects 53 and cognitive impairment 54 CCKBR is linked with posttraumatic stress disorder and synaptic plasticity 55 and PLEKHB1 is associated with Attention Deficit Hyperactivity Disorder 56 .…”

Section: Discussionmentioning

confidence: 99%

The domesticated brain: genetics of brain mass and brain structure in an avian species

Henriksen

Johnsson

Andersson

et al. 2016

Preprint

View full text Add to dashboard Cite

As brain size usually increases with body size it has been assumed that the two are tightly constrained and evolutionary studies have therefore often been based on relative brain size (i.e. brain size proportional to body size) rather than absolute brain size. The process of domestication offers an excellent opportunity to disentangle the linkage between body and brain mass due to the extreme selection for increased body mass that has occurred. By breeding an intercross between domestic chicken and their wild progenitor, we address this relationship by simultaneously mapping the genes that control inter-population variation in brain mass and body mass. Loci controlling variation in brain mass and body mass have separate genetic architectures and are therefore not directly constrained. Genetic mapping of brain regions indicates that domestication has led to a larger body mass and to a lesser extent a larger absolute brain mass in chickens, mainly due to enlargement of the cerebellum. Domestication has traditionally been linked to brain mass regression, based on measurements of relative brain mass, which confounds the large body mass augmentation due to domestication. Our results refute this concept in the chicken.Brain size variation across vertebrate species continues to fascinate evolutionary biologists, due in part to the cognitive and behavioral phenotypes it is thought to underlie. Such research is not limited to extant species, with the relationship between brain size and the fossil record capable of identifying the origins and development of avian species, and giving clues as to the evolutionary development of flight 1,2 . Most studies on brain size differences suggest some type of trade-off between the costs of developing and maintaining energetically expensive brain tissue and certain physiological variables (such as body size 3 , metabolic rate 4 and development time 5 ) or lifestyle variables (e.g. foraging ecology 6 and social environment 7 ). One physiological variable that correlates notably with brain size is body size 3 . As brain size usually increases as body size increases 8 it has been assumed that the two are tightly constrained during developmental growth 9 . Researchers have therefore often relied on relative rather than absolute brain size in correlative studies. The relationship between body size and brain size is, however, poorly understood and the use of allometry in brain size evolution studies has been criticized [10][11][12] . Understanding the genetics of brain size evolution is extremely pertinent to determine the relationship between brain size and body size. Most importantly, to what degree is there overlap (and potential pleiotropy) between the genes responsible for both. To date, studies on the genetic relationship between brain and body size are mostly limited to phylogenetic comparisons and measures of selection, and have failed to identify the overlap of the genetic architecture between these traits, especially using a within-species approach. The analysis of the rates of ev...

show abstract

Gene and stress history interplay in emergence of PTSD-like features

Cited by 11 publications

References 77 publications

Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder

Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder

Posttraumatic stress disorder: A metabolic disorder in disguise?

The domesticated brain: genetics of brain mass and brain structure in an avian species

Contact Info

Product

Resources

About