Chronic subordinate colony housing paradigm: A mouse model for mechanisms of PTSD vulnerability, targeted prevention, and treatment—2016 Curt Richter Award Paper

Reber, Stefan O.; Langgartner, Dominik; Foertsch, Sandra; Postolache, Teodor T.; Brenner, Lisa A.; Guendel, Harald; Lowry, Christopher A.

doi:10.1016/j.psyneuen.2016.08.031

Cited by 53 publications

(48 citation statements)

References 97 publications

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“…To address this point and statistically recapitulate Selye’s stress triad, or the later developing extended version of it, we assessed various physiological and immunological parameters from mice that have been exposed to either the CSC [41] paradigm or to SHC conditions. We first analyzed the data using PCA considering all data points and variables (S1 Table).…”

Section: Discussionmentioning

confidence: 99%

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

et al. 2018

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Selye defined stress as the nonspecific response of the body to any demand and thus an inherent element of all diseases. He reported that rats show adrenal hypertrophy, thymicolymphatic atrophy, and gastrointestinal ulceration, referred to as the stress triad, upon repeated exposure to nocuous agents. However, Selye’s stress triad as well as its extended version including reduced body weight gain, increased plasma glucocorticoid (GC) concentrations, and GC resistance of target cells do not represent reliable discriminatory biomarkers for chronic stress. To address this, we collected multivariate biological data from male mice exposed either to the preclinically validated chronic subordinate colony housing (CSC) paradigm or to single-housed control (SHC) condition. We then used principal component analysis (PCA), top scoring pairs (tsp) and support vector machines (SVM) analyses to identify markers that discriminate between chronically stressed and non-stressed mice. PCA segregated stressed and non-stressed mice, with high loading for some of Selye’s stress triad parameters. The tsp analysis, a simple and highly interpretable statistical approach, identified left adrenal weight and relative thymus weight as the pair with the highest discrimination score and prediction accuracy validated by a blinded dataset (92% p-value < 0.0001; SVM model = 83% accuracy and p-value < 0.0001). This finding clearly shows that simultaneous consideration of these two parameters can be used as a reliable biomarker of chronic stress status. Furthermore, our analysis highlights that the tsp approach is a very powerful method whose application extends beyond what has previously been reported.

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Section: Discussionmentioning

confidence: 99%

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

et al. 2018

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“…Data from animal studies indicate that environmental and gut microbial species elicit a significant impact on cognitive function, memory, and fundamental patterns of behaviour, such as social interaction and stress coping (40–43). Additionally, stress can influence the composition of the gut microbiota, and the bidirectional communication between microbiota and the CNS in turn influences stress reactivity (40, 41, 44). Alterations in microbiota have been shown to modulate plasticity-related (45–47), serotonergic (40, 45, 48, 49), and GABAergic (50–52) signaling systems in the CNS.…”

Section: Introductionmentioning

confidence: 99%

“…Alterations in microbiota have been shown to modulate plasticity-related (45–47), serotonergic (40, 45, 48, 49), and GABAergic (50–52) signaling systems in the CNS. Dysregulation of the gut microbiome (dysbiosis) therefore may influence risk of developing a disease, including stress- or trauma-related disorders (40, 41, 44). …”

Section: Introductionmentioning

confidence: 99%

“…Indeed, glucocorticoids induce the expansion of pathobionts, such as Helicobacter spp., a gram-negative bacterium, shown to enhance chronic inflammatory diseases (57). Mice exposed to psychological stressors exhibit expansion of Helicobacter spp., as determined by absolute abundance, evaluated using real-time quantitative PCR (58), or relative abundance (40, 41), and this effect can be prevented by the administration of a glucocorticoid receptor antagonist (58). Helicobacter spp.…”

Section: Introductionmentioning

confidence: 99%

“…induce colitis in IL-10 −/− mice, which lack adequate immunoregulation, an effect that may be due to overactivation of host immune defenses (59–61). Immunization with a heat-killed preparation of an immunoregulatory bacterium that increases Treg and anti-inflammatory cytokines, such as IL-10 and transforming growth factor beta (TGFβ) (62), has recently been shown to prevent stress-induced increases in a PTSD-like syndrome in mice (40, 41), suggesting that the balance of proinflammatory and anti-inflammatory or immunoregulatory microbial inputs could contribute to the risk of developing a PTSD-like syndrome.…”

Section: Introductionmentioning

confidence: 99%

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The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

Malan‐Müller²,

et al. 2017

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Objective Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls, to identify potential differences in microbial diversity or microbial community structure. Methods The Clinician Administered Posttraumatic Stress Disorder Scale for DSM-5 (CAPS-5) was used to diagnose PTSD according to DSM-5 criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA (rRNA) gene V3/V4 amplicons were generated and sequenced. Microbial community structure, alpha-diversity, and beta-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD. Results There were no differences between PTSD and TE control groups in alpha- or beta-diversity measures (e.g., alpha-diversity, Shannon index, t = 0.386, P = .70; beta diversity, based on analysis of similarities (ANOSIM), Bray Curtis test statistic = −0.033, P = .70); however, random forests analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher PTSD CAPS scores (r = −.387, P = .035). Conclusions In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.

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Inhibition of Sympathetic Activation by Delivering Calcium Channel Blockers from a 3D Printed Scaffold to Promote Bone Defect Repair

Jin

et al. 2022

Adv Healthcare Materials

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Enhancing osteogenesis by promoting neural network reconstruction and neuropeptide release is considered to be an attractive strategy for repairing of critical size bone defects. However, traumatic bone defects often activate the damaged sympathetic nervous system (SNS) in the defect area and release excessive catecholamine to hinder bone defect repair. Herein, a 3D printed scaffold loaded with the calcium channel blocker‐nifedipine is proposed to reduce the concentration of catecholamine present in the bone defect region and to accelerate bone healing. To this end, nifedipine‐loaded ethosome and laponite are added into a mixed solution containing sodium alginate, methacrylated gelatin, and bone mesenchymal stem cells (BMSCs) to prepare a cell‐laden scaffold using 3D bioprinting. The released nifedipine is able to close the calcium channels of nerve cells, thereby blocking sympathetic activation and ultimately inhibiting the release of catecholamine by sympathetic nerve cells, which further promotes the osteogenic differentiation and migration of BMSCs, inhibits osteoclastogenesis in vitro, and effectively improves bone regeneration in a rat critical‐size calvarial defect model. Therefore, the results suggest that sustained release of nifedipine from the scaffold can effectively block SNS activation, providing promising strategies for future treatment of bone defects.

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Chronic subordinate colony housing paradigm: A mouse model for mechanisms of PTSD vulnerability, targeted prevention, and treatment—2016 Curt Richter Award Paper

Cited by 53 publications

References 97 publications

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

Inhibition of Sympathetic Activation by Delivering Calcium Channel Blockers from a 3D Printed Scaffold to Promote Bone Defect Repair

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