Fluoxetine treatment prevents the inflammatory response in a mouse model of posttraumatic stress disorder

Kao, Chi-Ya; He, Zhisong; Zannas, Anthony S.; Hahn, Oliver; Kühne, Claudia; Reichel, Judith M.; Binder, Elisabeth B.; Wotjak, Carsten T.; Khaitovich, Philipp; Turck, Christoph W.

doi:10.1016/j.jpsychires.2016.02.003

Cited by 37 publications

(20 citation statements)

References 65 publications

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“…As shown in Table 2, the selected BioProjects were very heterogeneous and included several types of stress: acute 16,20 , sub-chronic 21 or chronic 22,23 restraint, cold swim 16 , sub-chronic 15 , or chronic 24 variable stress, unpredictable chronic mild stress 25 , chronic social defeat [26][27][28][29][30][31][32] , early life stress 29,32 , electric footshock (or contextual fear conditioning) [33][34][35] , auditory fear conditioning with or without immobilization 36 . Fear conditioning is a classical associative memory test in mice, however it is also widely used as preclinical animal model of PTSD, as it involves delivery of mild electric footshocks that represent an aversive experience, thus it was included in our selection of stressors 37 .…”

Section: Analysis Of Stress-related Changes In the Brain Transcriptommentioning

confidence: 99%

A gene expression atlas for different kinds of stress in the mouse brain

et al. 2020

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Stressful experiences are part of everyday life and animals have evolved physiological and behavioral responses aimed at coping with stress and maintaining homeostasis. However, repeated or intense stress can induce maladaptive reactions leading to behavioral disorders. Adaptations in the brain, mediated by changes in gene expression, have a crucial role in the stress response. Recent years have seen a tremendous increase in studies on the transcriptional effects of stress. The input raw data are freely available from public repositories and represent a wealth of information for further global and integrative retrospective analyses. We downloaded from the Sequence Read Archive 751 samples (SRA-experiments), from 18 independent BioProjects studying the effects of different stressors on the brain transcriptome in mice. We performed a massive bioinformatics re-analysis applying a single, standardized pipeline for computing differential gene expression. This data mining allowed the identification of novel candidate stress-related genes and specific signatures associated with different stress conditions. The large amount of computational results produced was systematized in the interactive “Stress Mice Portal”.

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Section: Analysis Of Stress-related Changes In the Brain Transcriptommentioning

confidence: 99%

A gene expression atlas for different kinds of stress in the mouse brain

et al. 2020

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“…Animal studies have investigated the impact of antiinflammatory therapies to alter PTSD-like features (65)(66)(67)(68)(69)(70). In a rat model of psychogenic stress with elevated cytokine levels, treatment with minocycline, an anti-inflammatory, antiapoptotic, and neuroprotective tetracycline agent, reduced levels of the cytokines IL-1, IL-6 and TNFa in the hippocampus, frontal cortex, and hypothalamus and reduced anxious behaviors (69).…”

Section: Preclinical Studiesmentioning

confidence: 99%

Metabolism, Metabolomics, and Inflammation in Posttraumatic Stress Disorder

Mellon

Gautam

Hammamieh

et al. 2018

Biological Psychiatry

140

110

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Posttraumatic stress disorder (PTSD) is defined by classic psychological manifestations, although among the characteristics are significantly increased rates of serious somatic comorbidities, such as cardiovascular disease, immune dysfunction, and metabolic syndrome. In this review, we assess the evidence for disturbances that may contribute to somatic pathology in inflammation, metabolic syndrome, and circulating metabolites (implicating mitochondrial dysfunction) in individuals with PTSD and in animal models simulating features of PTSD. The clinical and preclinical data highlight probable interrelated features of PTSD pathophysiology, including a proinflammatory milieu, metabolomic changes (implicating mitochondrial and other processes), and metabolic dysregulation. These data suggest that PTSD may be a systemic illness, or that it at least has systemic manifestations, and the behavioral manifestations are those most easily discerned. Whether somatic pathology precedes the development of PTSD (and thus may be a risk factor) or follows the development of PTSD (as a result of either shared pathophysiologies or lifestyle adaptations), comorbid PTSD and somatic illness is a potent combination placing affected individuals at increased physical as well as mental health risk. We conclude with directions for future research and novel treatment approaches based on these abnormalities.

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“…PTSD subjects who received pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) improved clinically and showed reductions in levels of the pro-inflammatory mediator IL-1 ( 68 ). In a mouse model of PTSD, treatment with the SSRI inhibitor fluoxetine prevented stress-induced inflammatory gene expression and improved PTSD-like symptoms ( 69 ). The results of this study indicated the role of inflammation in PTSD pathology and suggested using anti-inflammatory agents to treat PTSD.…”

Section: Ptsd Treatments In the Context Of Immune Imbalancesmentioning

confidence: 99%

Posttraumatic Stress Disorder: An Immunological Disorder?

2017

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Patients with posttraumatic stress disorder (PTSD) exhibit an increased state of inflammation. Various animal models for PTSD have shown some of the same immune imbalances as have been shown in human subjects with PTSD, and some of these studies are discussed in this review. However, animal studies can only indirectly implicate immune involvement in PTSD in humans. This review of mainly studies with human subjects focuses on dissecting the immunological role in the pathogenesis of PTSD following initial trauma exposure. It addresses both the inflammatory state associated with PTSD and the immune imbalance between stimulatory and inhibitory immune mediators, as well as variables that can lead to discrepancies between analyses. The concept of immunological treatment approaches is proposed for PTSD, as new treatments are needed for this devastating disorder that is affecting unprecedented numbers of Veterans from the long-standing wars in the Middle East and which affects civilians following severe trauma.

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Fluoxetine treatment prevents the inflammatory response in a mouse model of posttraumatic stress disorder

Cited by 37 publications

References 65 publications

A gene expression atlas for different kinds of stress in the mouse brain

A gene expression atlas for different kinds of stress in the mouse brain

Metabolism, Metabolomics, and Inflammation in Posttraumatic Stress Disorder

Posttraumatic Stress Disorder: An Immunological Disorder?

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