Model Of Posttraumatic Stress Disorder Research Articles

New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD).

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor.

Unraveling the Liver-Brain Axis: Resveratrol's Modulation of Key Enzymes in Stress-Related Anxiety.

Stress-related anxiety disorders and anxiety-like behavior in post-traumatic stress disorder (PTSD) are associated with altered neurocircuitry pathways, neurotransmitter systems, and the activities of monoamine and glucocorticoid-metabolizing enzymes. Resveratrol, a natural polyphenol, is recognized for its antioxidant, anti-inflammatory, and antipsychiatric properties. Previous studies suggest that resveratrol reduces anxiety-like behavior in animal PTSD models by downregulating key enzymes such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and monoamine oxidases (MAOs). However, the underlying mechanisms remain unclear. In this study, we explored the efficacy of resveratrol in treating stress-induced anxiety using a chronic predator stress model in rats. Resveratrol was administered intraperitoneally at 100 mg/kg following a 10-day stress exposure, and anxiety behavior was assessed with an elevated plus maze. Our results indicated that stress-related anxiety correlated with increased activities of brain MAO-A, MAO-B, and hepatic 11β-HSD-1, alongside elevated oxidative stress markers in the brain and liver. Resveratrol treatment improved anxiety behavior and decreased enzyme activities, oxidative stress, and hepatic damage. We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol's potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.

The epigenetic changes are affected by sex and valproic acid treatment in a rat model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) presents distinct sex-specific differences in both symptom expression and treatment outcomes, with the underlying biological mechanisms still remain unclear. Epigenetic modifications, particularly histone acetylation, have been increasingly recognized as critical factors in the pathophysiology of PTSD. Valproic acid (VPA), a potent histone deacetylase (HDAC) inhibitor, has shown promise in modulating epigenetic responses and improving therapeutic outcomes is PTSD, though its effect may differ between sexes.This study aimed to explore the sex-specific epigenetic changes in response to trauma and the impact of VPA treatment in a rat model of PTSD induced by predator scent stress. Sprague-Dawley rats of both sexes were randomly assigned to stressed and non-stressed groups and treated with either VPA (100 mg/kg) or vehicle. Anxiety levels were assessed using the elevated plus maze, followed by analysis of histone H3 and H4 acetylation, HDAC activity, and c-fos expression in the hippocampus.Our findings revealed that traumatic stress led to increased freezing time and anxiety levels, with more pronounced effects observed in females. Additionally, we have identified sex-specific differences in hippocampal epigenetic modifications; stressed females exhibited higher H3 acetylation, and VPA-treated stressed males showed increased H4 acetylation.These results highlight the importance of considering sex differences in the epigenetic mechanism underlying PTSD and suggest that personalized therapeutic approaches may be necessary to address these complexities.

Effects of voluntary, involuntary exercise and sertraline on anxiety, social and cognitive behavior in female rat model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is considered as a complex syndrome comprising extremely severe anxiety levels, social-interpersonal dysfunction, and cognitive impairment that may be based on severe traumatic events. Although PTSD is more prevalent in females than in males, most preclinical studies have been carried out in males. The present study investigated the effects of voluntary and involuntary exercise, as well as sertraline on behavioral deficits in a female nonhuman animal model of PTSD using the single-prolonged stress (SPS) paradigm. Female adult rats were exposed to SPS protocol (2-hour restrain, 20-minute forced swimming, 15-minute rest, and 2–3 minute diethyl ether exposure) and were then kept undisturbed. Following a 7-day undisturbed period, animals were subjected to a 10 min restraint (re-stress). SPS rats were treated with voluntary wheel running or moderate treadmill exercise (5 days/week) and/or the administration of sertraline (10 mg/kg/day) for four consecutive weeks. Behavioral assessments were conducted using the Elevated Plus Maze (EPM) test for anxiety, the Three-Chamber Social Test (3-CST) for social interaction, and the Morris Water Maze (MWM) test for spatial memory. Involuntary exercise combined with sertraline significantly increased time spent in the open arms of the EPM test (P < 0.001), and interaction with new rats in 3-CST (P < 0.001) compared to SPS rats. The voluntary exercise plus sertraline group showed a significant increase in entries into the training platform during the probe phase of the MWM test (P < 0.001) compared to SPS rats. Overall, sertraline combined with involuntary exercise was more effective than voluntary exercise plus sertraline in enhancing social interaction and reducing anxiety in the SPS model of PTSD. Conversely, voluntary exercise combined with sertraline provided greater benefits for spatial memory enhancement in female rats.

Effects of early life stress paired with adolescent alcohol consumption on two-bottle choice alcohol drinking behaviors in mice.

In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). We previously used an infant footshock model that produces stress-enhanced fear learning (SEFL) in rats and mice and increases aversion-resistant alcohol drinking in rats to explore this shared predisposition. The goal of the current study was to extend this model of comorbid PTSD and AUD to male and female C57BL/6J mice. Acute ELS was induced using 15 footshocks on postnatal day (PND) 17. In adulthood, alcohol drinking behavior was tested in one of three two-bottle choice drinking paradigms. In continuous access, mice were given 24 h access to 5% or 10% ethanol and water for five consecutive drinking sessions each. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions 3 h into the dark cycle. In intermittent access, mice were presented with 20% ethanol and water Monday, Wednesday, and Friday, for four consecutive weeks. In a fifth week of intermittent access drinking, increasing concentrations of quinine (10 mg/L, 100 mg/L, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Intermittent access drinking was tested with and without a period of adolescent drinking (PND 35). Infant footshock did not alter drinking in the continuous or limited access tasks. Adult consumption and preference were lower in the intermittent access task when adolescent drinking was included and there were ELS-induced differences in consumption of quinine-adulterated ethanol in females. Our results demonstrate that infant footshock followed by a period of adolescent drinking is a viable model of comorbid PTSD and AUD in rats and mice.

A Baseline Model of PTSD From the ACES Cohort.

Post-traumatic stress disorder (PTSD) is a primary military psychiatric condition with complex etiology including strong genetic and/or environmental influences. Environmental influences and demographics can play a role in supporting underlying genetic traits for clinical utility evaluation as risk modifying factors. We are undertaking an IRB approved study to evaluate polygenic scores of PTSD risk in the adverse childhood experience and serotonin (ACES) transporter cohort. Baseline demographic characteristics and statistical modeling of 291 active duty service members from ACES cohort were used and excluded individuals with traumatic brain injury-induced loss of consciousness, pre-deployment PTSD or anxiety disorder, and pre-deployment prescription of antidepressants or psychoactive medications. Summary of categorical and numerical variables were evaluated using chi-square and t-test, respectively. We model PTSD risk and associated scores using linear and logistic regressions. The ACES subset was 79.1% males, multi-ancestry, and mean age of 38.3 years. Most PTSD individuals received behavioral therapy (89.6%) and/or prescribed antidepressants (67%) had higher scores in ACES, combat exposure scales, PTSD checklist military version, neurobehavioral symptom inventory, Pittsburg sleep quality index, insomnia severity index, and composite autonomic symptom score surveys and were less likely to expect future deployment. A positive correlation between age, total months deployed, ACES, CES, PCL-M, and positive-PTSD diagnosis were consistent but not in older individuals, who were more likely and frequently deployed although increasing risk for combat exposure. Demographic characteristics of the ACES cohort fit a coherent model of risk for PTSD to evaluate polygenic scores. Additional research is merited to understand PTSD effects on these confounding factors.

Effects of the combination of bone marrow stromal cells and exercise on corticosterone, BDNF, IGF-1, and anxiety-like behaviour in a rat model of post-traumatic stress disorder: Comparable effects of exercise

Aim Post-traumatic stress disorder (PTSD) requires more effective treatment options with fewer side effects. Stem cell therapy, as a novel approach, has been investigated in the treatment of various diseases, including brain disorders. This study investigated the effects of bone marrow stromal cells (BMSCs) and the combination of BMSCs with exercise on corticosterone, BDNF and IGF-1, and anxiety-like behaviours in a male rat model of PTSD. Methods Male adult Wistar rats were subjected to PTSD induced by the single prolonged stress (SPS) model. 7 days after SPS, BMSCs were injected intravenously. The exercise started on day 11 and continued for 4 weeks. On day 40th, anxiety behaviour, corticosterone, BDNF, and IGF-1 were tested. p < 0.05 was considered as a significant level. Results The study showed that a combination of BMSCs and exercise significantly reduced anxiety-related behaviours, and alterations in BDNF, IGF-1, and corticosterone levels. Also, BMSCs alone significantly reduced some of the PTSD-induced impairments. However, exercise alone showed greater efficiency in comparison with BMSCs alone. Conclusion According to the results, although combination therapy effectively improved PTSD-related complications, exercise had relatively comparable effects on PTSD. Exercise has the potential to enhance the efficacy of BMSC therapy. Further research is required to determine whether BMSC therapy is sufficiently efficacious and safe in clinical settings.

Role of ventral tegmental area dopamine neurons in fear memory retention in post-traumatic stress disorder model rats

Ventral tegmental area (VTA) dopamine (DA) neurons have been found to substantially associate with post-traumatic stress disorder (PTSD) pathology, however, whether and how these DA neurons affect fear memory management in PTSD individuals remains largely unknown. In this study, we utilized auditory conditioned foot-shock to evaluate the fear memory retrieval and retention characteristics in a single prolonged stress-induced PTSD rat model. We employed chemogenetic technology to specifically activate VTA DA neurons to examine the freezing behaviors responding to the conditioned stimuli. In vivo extracellular electrophysiological analyses were used to identify VTA DA neuronal firing alterations due to the chemogenetic activation. The results demonstrated that PTSD model rats showed comparable fear memory retrieval (Day 2 after the conditioned foot-shock), but significant enhancements in fear memory retention (Day 8 after the conditioned foot-shock), compared to normal control rats. Chemogenetic activation of VTA DA neurons markedly diminished the retention of fear memory in PTSD model rats, which appeared concomitantly with increases in the firing activities of the DA neurons. These findings revealed that PTSD induced the persistence of fear memory, which could be attenuated by activation of VTA DA neurons. It is presumed that VTA dopaminergic signals may serve as a prospective option for PTSD treatment.

Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure. The characteristics of shocks (intensity and number) affect the strength of learning, but how these characteristics interact to influence conditioned and unconditioned consequences of shocks are poorly known. In this study, we aimed to investigate in adult male rats the impact of varying shock number and intensity on the endocrine and behavioral response to contextual fear conditioning and fear generalization to a novel environment markedly distinct from the shock context (i.e., fear generalization). Classical biological markers of stress (i.e., ACTH, corticosterone, and prolactin) were sensitive to manipulations of shock parameters, whereas these parameters had a limited effect on contextual fear conditioning (evaluated by freezing and distance traveled). In contrast, behavior in different novel contexts (fear generalization) was specifically sensitive to shock intensity. Notably, altered behavior in novel contexts markedly improved, but not completely normalized after fear extinction, hypoactivity apparently being the result of both conditioned and unconditioned effects of foot-shock exposure. The present results will contribute to a better understanding of shock exposure as a putative animal model of PTSD.

Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model.

Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation. However, its role in PTSD remains to be elucidated. In this study, we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus. Fluoxetine, but not risperidone or sertraline, has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities. Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling. Our data demonstrated the correlation between PTSD and abnormal myelination, suggesting that the oligodendroglial lineage could be a target for PTSD treatment.

Sex-specific alterations in visual properties induced by single prolonged stress model

Patients with post-traumatic stress disorder (PTSD) exhibit sex differences in symptomology, with women more likely to report higher rates of intrusive and avoidance symptoms than men, underscoring the need for sex-informed approaches to research and treatment. Our study delved into the sex-specific aspects of stress-induced visual impairments using the single prolonged stress (SPS) model, a partially validated rodent model for PTSD. Male SPS mice exhibit heightened optimal spatial frequency (SF) of primary visual cortex (V1) neurons, while female counterparts exhibit decreased optimal temporal frequency (TF) of V1 neurons. This phenomenon persisted until the 29th day after SPS modeling, and it may be the physiological basis for the observed increase in visual acuity in male SPS mice in visual water task. Furthermore, our study found that corticotropin-releasing factor receptor 1 regulated optimal TF and optimal SF of V1 in mice, but did not exhibit sex differences. These findings indicated that severe stress induces sex-specific effects on visual function.

The Effectiveness of the Single Object Burying Test in Assessing Hypervigilance-like Behavior in the Single Prolonged Stress Model of Post-Traumatic Stress Disorder (PTSD) in Male Sprague Dawley Rats

Abstract Introduction Post-traumatic stress disorder (PTSD) is recognized nowadays as a major public health issue. It arises as a long-term reaction to severe stressors considered to be life-threatening. It’s characterized by intrusive symptoms, avoidance, and hypervigilance. Although its prevalence is rather high, the mechanisms behind this serious condition are little understood, and its treatment is currently challenging. To get insights into this disorder, a variety of PTSD models were developed in the last 15 years as well as several tests have been proposed to assess the PTSD-like behaviors in these animal models. The single object burying test (OBT) was used to examine the hypervigilant behavior in electric shock animal model of PTSD. To the best of our knowledge, no prior studies have utilized the OBT to assess hypervigilance in the traditional single prolonged stress (SPS) animal model of PTSD. Our study aims to compare the behavioral response of the SPS-exposed and SPS-unexposed rats in the OBT. Methods This study employed the single prolonged stress (SPS) model to induce PTSD in male Sprague-Dawley rats (n = 12 rats, divided as control group = 6 rats, and SPS group = 6 rats) to investigate whether the single object burying test can detect the hypervigilance like behavior in the SPS rats as compared to control group. Parameters used are the percentage of time spent manipulating the object and the percentage of time spent burying the object. Results SPS rats demonstrated decrease in the percentage of time spent manipulating the object and increase in the percentage of time spent burying the object as compared to control group in the OBT. These responses are interpreted as hypervigilance like behavior. Conclusion The OBT can be considered a successful test in assessing hypervigilance of the rats exposed to the SPS animal model of PTSD

Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD.

MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the aim of this study was to explore the role of oxytocinergic signaling and neuroinflammatory markers in the therapeutic effects of MDMA. To achieve this, male rats were subjected to a model of PTSD involving exposure to shock and situational reminders. MDMA was microinjected into the medial prefrontal cortex (mPFC) before extinction training, followed by behavioral tests assessing activity levels, anxiety, and social function. Our findings indicate that MDMA treatment facilitated fear extinction and mitigated the shock-induced increase in freezing, as well as deficits in social behavior. Shock exposure led to altered expression of the gene coding for OXT-R and neuroinflammation in the mPFC and basolateral amygdala (BLA), which were restored by MDMA treatment. Importantly, the OXT-R antagonist L-368,899 prevented MDMA's therapeutic effects on extinction and freezing behavior. In conclusion, MDMA's therapeutic effects in the PTSD model are associated with alterations in OXT-R expression and neuroinflammation, and MDMA's effects on extinction and anxiety may be mediated by oxytocinergic signaling.

Longitudinal associations between posttraumatic stress disorder, separation anxiety, and rumination among adolescents: Disentangling within-person and between-person associations.

Posttraumatic stress disorder (PTSD) and separation anxiety often show high comorbidity after trauma, which complicates the course of disease and treatment response. However, it is unclear how PTSD and separation anxiety comorbidity occur. According to the cognitive model of PTSD, rumination may be a key cognitive process linking the two constructs. Thus, this study aimed to examine the relation between PTSD and separation anxiety and to assess the mediating role of rumination in this relation among adolescents after trauma. A follow-up survey was conducted among 204 adolescent survivors of the Ya'an earthquake, at 6 months (T1), 12 months (T2), and 18 months (T3). A random-intercept cross-lagged panel model was used for data analysis to disentangle within-person dynamics from stable between-person differences. The results showed that at the within-person level, PTSD increased separation anxiety via rumination, and early PTSD further exacerbated later PTSD through increased rumination and separation anxiety. These findings highlight the mediating role of rumination, elucidate the relation between PTSD and separation anxiety, and provide theoretical support for the development of transdiagnostic clinical interventions and treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of early social isolation and adolescent single prolonged stress on anxiety-like behaviors and voluntary ethanol consumption in female Long Evans rats.

Exposure to stress during childhood and adolescence is a risk factor for alcohol use disorder (AUD) and comorbid conditions, including posttraumatic stress disorder (PTSD). We previously established an adolescent social isolation (SI) model that leads to the emergence of a wide range of behavioral risk factors for AUD, including increased anxiety-like behavior, locomotor activity, and ethanol consumption in male and female rats. Here, we sought to test the hypothesis that SI may increase vulnerability to single prolonged stress (SPS), a rodent model of PTSD. Female Long Evans rats (n = 8/group) were either single-housed or group-housed (GH) (4/cage) on postnatal day 21. One week later, rats underwent testing in the open field test (OFT), elevated plus-maze (EPM), and successive alleys test (SAT). Following initial behavioral testing, a subset of SI/GH rats were exposed to SPS. All rats were then tested on the novelty-suppressed feeding test (NSFT) followed by fear conditioning and home cage two-bottle choice to assess ethanol consumption. SI significantly increased activity in the OFT and anxiety-like behavior on the SAT, but not the EPM. While SI and SPS alone had no effect on the NSFT, exposure to both stressors significantly increased approach latency. Complex effects of stress history were observed across a 3-day fear conditioning paradigm and no group differences were observed with home cage ethanol consumption, regardless of prior ethanol exposure. The results from this study provide novel evidence that SI interacts with SPS in female rats to influence behavior in assays of unconditioned anxiety-like behavior (NSFT) and conditioned fear. Surprisingly, stress exposure had no effect on home cage ethanol consumption. Ultimately, these models provide useful avenues to examine the interaction between stressful experiences, alcohol exposure, biological sex, and the neurobiological adaptations underlying potential risk factors for psychiatric conditions.

Beta-adrenergic signaling and T-lymphocyte-produced catecholamines are necessary for interleukin 17A synthesis.

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that also presents with neuroimmune irregularities. Patients display elevated sympathetic tone and are at an increased risk of developing secondary autoimmune diseases. Previously, using a preclinical model of PTSD, we demonstrated that elimination of sympathetic signaling to T-lymphocytes specifically limited their ability to produce pro-inflammatory interleukin 17A (IL-17A); a cytokine implicated in the development of many autoimmune disorders. However, the mechanism linking sympathetic signaling to T-lymphocyte IL-17A production remained unclear. Using a modified version of repeated social defeat stress (RSDS) that allows for both males and females, we assessed the impact of adrenergic receptor blockade (genetically and pharmacologically) and catecholamine depletion on T-lymphocyte IL-17A generation. Additionally, we explored the impact of adrenergic signaling and T-lymphocyte-produced catecholamines on both CD4+ and CD8+ T-lymphocytes polarized to IL-17A-producing phenotypes ex vivo. Only pharmacological inhibition of the beta 1 and 2 adrenergic receptors (β1/2) significantly decreased circulating IL-17A levels after RSDS, but did not impact other pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IL-10). This finding was confirmed using RSDS with both global β1/2 receptor knock-out mice, as well as by adoptively transferring β1/2 knock-out T-lymphocytes into immunodeficient hosts. Furthermore, ex vivo polarized T-lymphocytes produced significantly less IL-17A with the blockade of β1/2 signaling, even in the absence of exogenous sympathetic neurotransmitter supplementation, which suggested T-lymphocyte-produced catecholamines may be involved in IL-17A production. Indeed, pharmacological depletion of catecholamines both in vivo and ex vivo abrogated T-lymphocyte IL-17A production demonstrating the importance of immune-generated neurotransmission in pro-inflammatory cytokine generation. Our data depict a novel role for β1/2 adrenergic receptors and autologous catecholamine signaling during T-lymphocyte IL-17A production. These findings provide a new target for pharmacological therapy in both psychiatric and autoimmune diseases associated with IL-17A-related pathology.

Validating the Spanish translation of the posttraumatic stress disorder checklist (PCL-5) in a sample of individuals with traumatic brain injury.

There is controversy regarding the comorbidity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The present study translated the PTSD Checklist for DSM-5 (PCL-5) to Spanish and validated it in a sample of patients with TBI 6 months after the injury. The study included 233 patients (162 males and 71 females) recruited from four Spanish hospitals within 24 h of traumatic brain injury. A total of 12.2% of the sample met the provisional PTSD diagnostic criteria, and the prevalence was equal between male and female participants. The analysis confirmed the internal consistency of the translated instrument (α = 0.95). The concurrent validity of the instrument was confirmed based on high correlation coefficients of 0.7 and 0.74 with the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire (PHQ-9), respectively. Exploratory factor analysis also confirmed that the items on the PCL-5 can be differentiated from the GAD-7 and PHQ-9 items. Confirmatory factor analysis (CFA) was used to examine the structural validity of the Spanish translation of the PCL-5 with three different models. CFA partially confirmed the four-factor PTSD model, whereas both the six-factor anhedonia model and the seven-factor hybrid model showed adequate fit. However, the difference between the anhedonia and hybrid models was not statistically significant; moreover, both models showed signs of overfitting. Therefore, the utility of these models should be reexamined in future studies. Overall, the results suggest that the Spanish translation of the PCL-5 is a reliable and valid instrument for screening PTSD symptoms among Spanish TBI patients. The Spanish translation of the PCL-5 is also presented in the manuscript.

SOURCES OF SUPEROXIDE ANION RADICAL IN SMALL INTESTINE TISSUES IN RATS SUBJECTED TO SURGICAL TRAUMA SIMULATED UNDER EXPERIMENTAL MODEL OF POSTTRAUMATIC STRESS DISORDER

The sources of superoxide anion radical (.О ) in the tissues of the small intestine in rats subjected to surgical trauma simulated under an experimental model of posttraumatic stress disorder (PTSD) were investigated. The study involved 42 white Wistar rats weighing 210-230 g, divided into 6 groups: group 1 comprised intact animals, group 2 included animals with the PTSD induced through single-prolonged stress (SPS), group 3 consisted of rats subjected to a sham surgical operation, group 4 comprised animals undergoing laparotomy, group 5 involved rats undergoing a sham surgical operation following SPS, and group 6 included animals undergoing laparotomy under modeled SPS. The rate of .О generation in the small intestine homogenate was measured spectrophotometrically using the nitroblue tetrazolium test. The .О production by NADPH-dependent (microsomal and NO synthase) electron transport chains (ETC), NADH-dependent (mitochondrial) ETC and leukocyte NADPH oxidase was assessed. The findings obtained have demonstrated that experimental SPS modeling leads to an increase in oxidative stress in the small intestine tissues of rats. This is manifested by an increase in the rate of .О formation with the participation of microsomes, mitochondria and leukocyte NADPH oxidase. On the 7th day after laparotomy under the experimental PTSD model, the .О production in the tissues of the small intestine by different sources (microsomes, mitochondria and leukocyte NADPH oxidase) exceeds their values obtained after a single laparotomy or after performing a sham operation under single long-term stress.

Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice.

Post-traumatic stress disorder (PTSD) is a hypermnesic condition that develops in a subset of individuals following exposure to severe trauma. PTSD symptoms are debilitating, and include increased anxiety, abnormal threat generalization, and impaired extinction. In developing treatment strategies for PTSD, preclinical studies in rodents have largely focused on interventions that target post-encoding memory processes such as reconsolidation and extinction. Instead, here we focus on forgetting, another post-encoding process that regulates memory expression. Using a double trauma murine model for PTSD, we asked whether promoting neurogenesis-mediated forgetting can weaken trauma memories and associated PTSD-relevant behavioral phenotypes. In the double trauma paradigm, consecutive aversive experiences lead to a constellation of behavioral phenotypes associated with PTSD including increases in anxiety-like behavior, abnormal threat generalization, and deficient extinction. We found that post-training interventions that elevate hippocampal neurogenesis weakened the original trauma memory and decreased these PTSD-relevant phenotypes. These effects were observed using multiple methods to manipulate hippocampal neurogenesis, including interventions restricted to neural progenitor cells that selectively promoted integration of adult-generated granule cells into hippocampal circuits. The same interventions also weakened cocaine place preference memories, suggesting that promoting hippocampal neurogenesis may represent a broadly useful approach in hypermnesic conditions such as PTSD and substance abuse disorders.