Autoimmune and neuropsychiatric phenotypes in a Mecp2 transgenic mouse model on C57BL/6 background.

Introduction: Systemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable. Methods: C57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting. Results: B6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3. Discussion: Collectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.

Acceptance of COVID-19 vaccination in a sample of Middle Eastern and North African (MENA) Houston residents.

BACKGROUND: COVID-19 vaccination has averted a significant number of deaths in the United States, but vaccination hesitancy continues to be a problem. Therefore, examining vaccination acceptance and/or hesitancy in local communities is critical. METHODS: A quantitative survey and a multivariable logistic regression model was utilized to determine predictors of COVID-19 vaccination in Middle Eastern and North African (MENA) origin Houston residents. The outcome of interest was COVID-19 vaccination status (vaccinated versus not vaccinated). Covariates included: demographics, health, and COVID-19 factors. Statistical analyses included SAS version 9.4 at a priori significance level of 0.05. RESULTS: The overall vaccine acceptance rate was significantly high in this population subset (N = 366), with 77.60% vaccinated, and 22.40% not vaccinated. MENA individuals with some college degrees were less likely to report vaccination than those with a graduate degree [Odds Ratio (OR): 0.18; 95% Confidence Interval (CI): 0.04, 0.77]. Homeowners were more likely to get vaccinated than renters (OR: 2.58; 95%CI: 1.17, 5.68). Individuals practicing Islamic faith were more likely to get vaccinated than other religious affiliations (OR: 3.26; 95%CI: 1.15, 9.19). Individuals with hypertension were less likely to get vaccinated than those without it (OR: 0.34; 95%CI: 0.13, 0.92), and those with anxiety were more likely to get vaccinated than those without anxiety (OR: 4.23; 95%CI: 1.68, 10.64). CONCLUSIONS: Health status, education level, financial stability, and religious affiliation are some of the determining factors that potentially influence vaccination acceptance/hesitancy among the MENA community.

Understanding Mental Health Status of Syrian Refugee and Jordanian Women: Novel Insights from a Comparative Study.

(1) Background: War and displacement are well-known predictors of negative mental health outcomes among affected populations. This is especially relevant for refugees of war, particularly women, who often repress their mental health needs due to family responsibilities, social stigma, and/or cultural pressures. In this study, we compared the mental health status of urban Syrian refugee women (n = 139) with local Jordanian women (n = 160). (2) Methods: Psychometrically validated Afghan Symptom Checklist (ASC), Perceived Stress Scale (PSS), and Self-Report Questionnaire (SRQ) examined psychological distress, perceived stress, and mental health, respectively. (3) Results: According to independent t-tests, Syrian refugee women scored higher than Jordanian women on the ASC [mean score (SD): 60.79 (16.67) vs. 53.71 (17.80), p < 0.001], PSS [mean score (SD): 31.59 (8.45) vs. 26.94 (7.37), p < 0.001], and SRQ [mean score (SD): 11.82 (4.30) vs. 10.21 (4.72), p = 0.002]. Interestingly, both Syrian refugee and Jordanian women scored higher than the clinical cutoff in the SRQ. Regression analyses indicated that more educated women were less likely to score high on the SRQ (ß = -0.143, p = 0.019), particularly in the anxiety and somatic symptoms subscale (ß = -0.133, p = 0.021), and were less likely to exhibit symptoms of ruminative sadness (ß = -0.138, p = 0.027). Employed women were more likely to exhibit high coping ability than unemployed women (ß = 0.144, p = 0.012). (4) Conclusions: Syrian refugee women scored higher than Jordanian women in all used mental health scales. Access to mental health services and enhancing educational opportunities would help mitigate perceived stress and may enhance stress-coping abilities.

Breast Cancer Beliefs and Screening Practices among Syrian Refugee Women and Jordanian Women.

Despite significant declines in breast cancer (BC) incidence in the West, this disease is widespread in Jordan, where cancer detection occurs at much advanced stages. This is particularly concerning for Syrian refugee women resettled in Jordan, who are less likely to undergo cancer preventative procedures because of poor health literacy and lack of health services access. The present work assesses and compares breast cancer awareness and breast cancer screening behaviors among Syrian refugee women and Jordanian women residing close to the Syrian-Jordanian border city of Ar-Ramtha. A cross-sectional survey was conducted using a validated Arabic version of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ). A total of 138 Syrian refugee women and 160 Jordanian women participated in the study. Results indicate that 93.6% of Syrian refugee women and Jordanian women ≥ 40 years of age reported never having undergone a mammogram. Syrian refugee women and Jordanian women reported low attitudes toward general health checkup (mean score for Syrian refugees 45.6 vs. 42.04 among Jordan women; p = 0.150). Barriers for BC screening were higher among Syrian refugees (mean score = 56.43) than Jordanian women (mean score = 61.99, p = 0.006). Women with higher education were more likely to report fewer barriers to screening (p = 0.027). The study documents a significant lack of BC screening awareness among Syrian refugee women and Jordanian women, indicating that future work is needed to alter current attitudes towards mammograms and early detection measures especially for Syrian refugee women and Jordanian women residing in rural areas of Jordan.

Early-Life Sleep Deprivation Enhanced Alcohol Consumption in Adolescent Rats.

Evidence in the literature suggests that sleep deprivation during early-life developmental stages, by impacting important processes such as the reward circuit maturation, may increase the vulnerability for alcohol and substance use. The mechanisms involved are not fully understood. In this study, utilizing our previously established model, we examined the impact of early-life sleep deprivation on alcohol consumption in adolescent rats. Male Sprague Dawley rats served as either the control (CON) or sleep-deprived (SD) group. Sleep deprivation was induced using a Pinnacle automated sleep deprivation apparatus. The SD group of rats was sleep deprived for 6-8 h/day for 14 days from postnatal day (PND)19 to PND32. At PND33, anxiety- and depression-like behaviors were assessed in rats using elevated plus maze and sucrose splash test, respectively. At PND39, alcohol consumption was assessed in rats for five consecutive days using the two-bottle choice paradigm, water versus 5% ethanol. SD rats exhibited significant anxiety- and depression-like behaviors as compared to CON rats. Interestingly, SD rats consumed a larger volume of alcohol when compared to CON rats, which was significantly higher at day 5 (mean of alcohol consumption (ml) ± SD; CON = 6.67 ± 3.42; SD = 19.00 ± 6.05, p = 0.0126). SD rats also showed high preference for alcohol over water, which was significantly higher at day 5 (mean of alcohol preference (%) ± SD; CON = 26.85 ± 14.97; SD = 57.69 ± 5.61, p = 0.014). Our data suggest that early-life sleep deprivation enhanced alcohol consumption in adolescent rats.

Early Life Sleep Deprivation and Brain Development: Insights From Human and Animal Studies.

Adequate sleep especially during developmental stages of life, is considered essential for normal brain development and believed to play an important role in promoting healthy cognitive and psychosocial development, while persistent sleep disturbances and/or sleep deprivation during early life are believed to trigger many mental ailments such as anxiety disorders, depression, and cognitive impairment. Initially it was suggested that adverse mental health conditions adversely affect sleep, however, it is now accepted that this association is bidirectional. In fact, sleep disturbances are listed as a symptom of many mental health disorders. Of special interest is the association between early life sleep deprivation and its negative mental health outcomes. Studies have linked persistent early life sleep deprivation with later life behavioral and cognitive disturbances. Neurobiological underpinnings responsible for the negative outcomes of early life sleep deprivation are not understood. This is a significant barrier for early therapeutic and/or behavioral intervention, which can be feasible only if biological underpinnings are well-understood. Animal studies have provided useful insights in this area. This article focusses on the knowledge gained from the research conducted in the area of early life sleep deprivation, brain development, and behavioral function studies.

Displacement and Isolation: Insights from a Mental Stress Survey of Syrian Refugees in Houston, Texas, USA.

(1) Background: Syrians are the largest forcibly displaced population in the world. Approximately 20,000 Syrian refugees have resettled in the United States (US) since the civil war in Syria began in 2011, with an estimated 130 families resettling in Houston, Texas. We conducted a pilot study with the objective of examining the physical and mental well-being of the Houston Syrian refugee population. (2) Methods: Online surveys were conducted using psychometrically valid instruments including Afghan Symptom Checklist (ASC), Refugee Post-Migration Stress Scale (RPMSS), Perceived Stress Scale (PSS), and Self-Report Questionnaire (SRQ) (3) Results: According to independent t-tests, Syrian refugee females scored higher than males on ASC (37.78 vs. 31.64, p = 0.0446), particularly in the subscales of sadness with social withdrawal (28.89 vs. 24.31, p = 0.0495), and stress-induced reactivity (6.56 vs. 4.86, p = 0.0004). Similarly, females scored higher than males in RPMSS (60.54 vs. 45.15, p = 0.0022), including the social strain domain (8.08 vs. 5.18, p = 0.0204). In PSS and SRQ, Syrian refugee females reported comparable stress and distress scores as males. (4) Conclusions: Syrian refugee females reported higher stress and distress than males. Displacement from their home country and social strain were the major sources of stress in Syrian refugee females, as indicated in RPMSS.

Perception Regarding Knowledge of COVID-19 Prevention in a Sample of a Middle Eastern and North African (MENA) Community in Houston, Texas, USA.

(1) Background: Knowledge of COVID-19 prevention among communities is the first step towards protective behaviors. The objective of this study was to assess COVID-19 prevention knowledge among a Middle Eastern and North African community in Houston, Texas. (2) Methods: A cross-sectional study was conducted using a validated quantitative survey; survey questions consisted of three parts: COVID-19 specific questions, general health questions, and sociodemographic questions. A multivariable logistic regression model was used to determine predictors of perception of knowledge on preventing COVID-19 spread. The outcome of interest comprised of "good/excellent" versus "average and below" knowledge. (3) Results: A total of 366 participants (66.39% males) completed the survey. A univariate analysis demonstrated significant differences in self-reported COVID-19 prevention knowledge among those with and without health insurance, different ages, level of knowledge, and perceived severity of COVID-19 infection. In the multivariate logistic regression, two predictors were identified: those in the 18-25-year-old group were more likely to have "excellent/good" knowledge on COVID-19 spread compared to the ≥40-year-old group (OR: 6.36; 95% CI: 1.38, 29.34). Those who somewhat agree with knowing how to protect themselves from COVID-19 were more likely to have "excellent/good" knowledge of preventing COVID-19 spread compared to those that neither agree nor disagree or disagree (OR: 7.74; 95% CI: 2.58, 23.26). (4) Conclusions: Younger adults reported higher knowledge of COVID-19 prevention.

The coping strategies followed by university students to mitigate the COVID-19 quarantine psychological impact.

Different strategies were followed to control the spread of the COVID-19 disease worldwide. Jordan declared a military-enforced curfew for three months, which successfully controlled the disease spreading. However, the curfew impacted several aspects of students' lives and personalities. This study discusses the impact of the COVID-19 curfew restrictions on university students' mental health, as this area was not fully discussed in previous studies. An online survey was distributed to cover the psychological symptoms and coping strategies of university students. Most of them experienced short temper, anxiety, and sleep problems. Female students expressed more psychological symptoms than males, they managed their stress by sleeping, studying, and worshiping. Whereas male students were working, exercising, and playing video games. A distinct interest was noticed among students of different ages. Young students (18-25 years) expressed unhappiness and distress-like symptoms; they advocated sleeping and playing video games. While elder students (>26 years) had anxiety, sleep problems, and short tempers, they managed their symptoms by studying, exercising, and worshiping. The curfew restrictions have negatively impacted the mental health of female and younger students more than other categories. These research outcomes will help decision-makers to implement healthy coping strategies to be followed during unusual conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-01833-1.

Simulated vehicle exhaust exposure induces sex-dependent behavioral deficits in rats.

Chronic exposure to vehicle exhaust emissions are known to cause several adverse health effects. In this study, we examined the impact of several parameters of behavioral, cardiovascular and biochemical functions upon exposure of pro-oxidants CO2, NO2 and CO (simulated vehicle exhaust exposure: SVEE) in male and female rats. Adult rats were subjected to SVEE or ambient air in whole body chambers (5 h/day, 2 weeks). Male, but not female, rats developed memory deficits, and exhibited anxiety- and depression-like behavior, accompanied with significantly high levels of serum corticosterone, oxidative stress, and inflammatory markers (CRP and TNFα), associated with lower levels of total antioxidant capacity, glutathione, glyoxalase and superoxide dismutase (SOD) activities. Brain region-specific downregulation of Cu/Zn SOD, Mn SOD, GSR, PKCα, ERK1/2, CaMKIV, CREB, BDNF and NMDAR subunit protein expression were also observed in male, but not female, rats. Blood pressure, heart rate and eGFR were not negatively impacted by SVEE. Our results suggest that SVEE, through its pro-oxidant content, induces oxido-inflammation in susceptible brain regions in a sex-dependent manner.

Understanding stress: Insights from rodent models.

Through incorporating both physical and psychological forms of stressors, a variety of rodent models have provided important insights into the understanding of stress physiology. Rodent models also have provided significant information with regards to the mechanistic basis of the pathophysiology of stress-related disorders such as anxiety disorders, depressive illnesses, cognitive impairment and post-traumatic stress disorder. Additionally, rodent models of stress have served as valuable tools in the area of drug screening and drug development for treatment of stress-induced conditions. Although rodent models do not accurately reproduce the biochemical or physiological parameters of stress response and cannot fully mimic the natural progression of human disorders, yet, animal research has provided answers to many important scientific questions. In this review article, important studies utilizing a variety of stress models are described in terms of their design and apparatus, with specific focus on their capabilities to generate reliable behavioral and biochemical read-out. The review focusses on the utility of rodent models by discussing examples in the literature that offer important mechanistic insights into physiologically relevant questions. The review highlights the utility of rodent models of stress as important tools for advancing the mission of scientific research and inquiry.

Protective effect of propranolol and nadolol on social defeat-induced behavioral impairments in rats.

Benzodiazepines and SSRIs are considered as standard treatment options for anxiety and depression, hallmarks of Post-Traumatic Stress Disorder (PTSD), although their use is often limited by adverse effects. While promising evidence emerged with ß-adrenergic receptor (ß-AR) antagonists (or 'ß-blockers') and PTSD relief, efficacy issues dampened the excitement. However, we believe it is premature to completely eliminate a beneficial role of ß-blockers. Our previous work has suggested that social defeat (SD) results in anxiety-like and depression-like behaviors in rats. Here, using the SD paradigm, we examined the effect of several ß-adrenergic receptor antagonists (propranolol, nadolol, bisoprolol) on these behaviors in rats. Following acclimatization, Sprague-Dawley rats received no treatment (for control groups) or treated with ; propranolol (50 mg/kg/day in water), or nadolol (18 mg/kg/day in rats' chow), or bisoprolol (15 mg/kg/day in water). The treatment lasted for 36 days, following which rats were subjected to SD/control exposures (1 week). Later, anxiety-like and depression-like behaviors, social interaction and learning-memory function tests were conducted. SD rats exhibited anxiety- and depression-like behavior as well as learning-memory impairment. Propranolol and nadolol protected SD rats from exhibiting anxiety-or depression-like behaviors. Bisoprolol treatment did not mitigate SD-induced behavioral impairments in rats. Nadolol, propranolol or bisoprolol have no effect in attenuating SD-induced memory function tests. These results suggest that certain 'ß-blockers' have the potential to mitigate the negative psychological effects of traumatic events.

Sleep deprivation, oxidative stress and inflammation.

Adequate sleep is essential for normal brain function, especially during early life developmental stages as postnatal brain maturation occurs during the critical period of childhood and adolescence. Therefore, sleep disturbance and/or deficit during this period can have detrimental consequences. Many epidemiological and clinical studies have linked early life sleep disturbance with occurrence of later life behavioral and cognitive impairments. Role of oxidative stress and inflammation has been implicated in sleep deprivation-related impairments. This review article presents a detailed description of the current state of the literature on the subject.

The Influence of Coronavirus Diseases 2019 (COVID-19) Pandemic and the Quarantine Practices on University Students' Beliefs About the Online Learning Experience in Jordan.

Coronavirus Disease 2019 (COVID-19) is a contagious disease that affects the respiratory system. In addition to the severe effects of the disease on health, the pandemic caused a negative impact on basic needs and services, employment, education, and economy worldwide. In Jordan, the whole country locked down, and quarantine was enforced by the military forces, which successfully controlled the spread of the disease. This research aims to study the influence of the COVID-19 pandemic and its associated quarantine on university students' beliefs about online learning practice in Jordan. An online descriptive survey involved questions that covered students' demographic information, student's basic and advanced knowledge about COVID-19, students' online learning experience during the quarantine, and finally students' views on the enforced quarantine practice in Jordan. Results showed that students have a good knowledge (>50%) about the COVID-19 basic information and a moderate knowledge (<50%) regarding COVID-19 advanced information. In general, students were pessimistic about the future of COVID-19 both locally and worldwide. Although some students acknowledged that they learned new skills in the fields of electronics, informatics, and computer software during the pandemic, most of them were unsatisfied about the quality and quantity of the given material, online exams, and the evaluation processes. Unfortunately, most of the students faced internet technical problems or challenges to electronic accessibility. The majority of the participants (>90%) supported the military-enforced quarantine implemented in the country despite the hard time the students had during the quarantine. We conclude that university students were able to protect themselves from COVID-19 through their good knowledge about the infectious disease and their commitment to follow the rules imposed by the Government of Jordan. Nevertheless, the challenges caused by the pandemic and its associated quarantine, combined with the sudden unprecedented online experience, negatively impacted students' thoughts and beliefs about the online learning experience during the quarantine. Further studies need to be performed in this context. We hope our results will help decision-makers better understand the students' attitudes and motivation toward online learning and how this will affect their future plans and decisions.

Stress, psychiatric disorders, molecular targets, and more.

Mental health is central to normal health outcomes. A widely accepted theory is that chronic persistent stress during adulthood as well as during early life triggers onset of neuropsychiatric ailments. However, questions related to how that occurs, and why are some individuals resistant to stress while others are not, remain unanswered. An integrated, multisystemic stress response involving neuroinflammatory, neuroendocrine, epigenetic and metabolic cascades have been suggested to have causative links. Several theories have been proposed over the years to conceptualize this link including the cytokine hypothesis, the endocrine hypothesis, the oxidative stress hypothesis and the oxido-neuroinflammation hypothesis. The data discussed in this review describes potential biochemical basis of the link between stress, and stress-induced neuronal, behavioral and emotional deficits, providing insights into potentially novel drug targets.

Early Life Sleep Deprivation: Role of Oxido-Inflammatory Processes.

The adverse consequences of early-life sleep deprivation on mental health are well recognized, yet many aspects remain unknown, therefore, animal studies can offer useful insights. Male Sprague-Dawley rats at postnatal day (PND) 19 were subjected to sleep deprivation (SD) for 14 days (6-8 hours/day). Control (CON) rats were gently handled. Behavior tests were done on PND33, PND60 and PND90. SD rats exhibited anxiety-like behavior at PND33 and PND60, when compared to CON rats. Depression-like behavior was observed at PND90. Evaluation of oxidative stress and inflammatory markers revealed interesting results. Plasma 8-isoprostane and antioxidant defense enzymes; hemeoxygenase-1, superoxide dismutase, glutathione peroxidase in the prefrontal cortex (PFC), were upregulated in SD rats at PND33 but not at PND90. PFC interleukin-6 protein expression was elevated at PND33 and PND90. PFC mitogen activated protein kinase phosphatase-1 (MKP-1) and p-38 protein expression were upregulated at PND90. PFC expression of glutamate receptor subunits, post synaptic density protein (PSD-95), calcium/calmodulin-dependent protein kinase (CaMKII), and extracellular signal-regulated kinase (ERK1/2), were significantly reduced in SD rats at PND33 and PND90. PFC brain derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB) were reduced in SD rats at PND90. Our postulation is that SD by increasing PFC oxido-inflammation, negatively affects glutamate receptor subunits and PSD95 expression, which disrupts synapse formation and maturation, potentially causing anxiety-like behavior at PND33. Oxido-inflammation further results in MKP-1 and CaMKII-mediated blockade of ERK1/2 activation, which inhibits CREB dependent BDNF expression. This most likely disrupts neuronal circuit development, leading to depression-like behavior at PND90.

Behavioral and cognitive impact of early life stress: Insights from an animal model.

BACKGROUND: Children subjected to traumatic events during childhood are reported to exhibit behavioral and cognitive deficits later in life, often leading to post-traumatic stress disorder (PTSD) and major depression. Interestingly, some children continue to remain normal despite being exposed to the same risk factors. These trauma-related behavioral and cognitive profiles across different stages of life are not well understood. Animal studies can offer useful insights. OBJECTIVE: The goal of this study was to determine the impact of early life exposure to traumatic events on behavioral and cognitive profile in rats by tracking the behavior of each rat at different ages. METHODS: We utilized the single prolonged stress (SPS), a rodent model of PTSD, to study the effects of early life stress. Male Sprague-Dawley rats were exposed to SPS on post-natal day (PND) 25. Tests to assess anxiety- and depression-like behavior, as well as learning and memory function were performed at PND32, 60 and 90. RESULTS: Rats exposed to SPS exhibited both anxiety- and depression-like behavior at PND32. And, short-term (STM) but not long-term memory (LTM) was impaired. Rats exposed to SPS at PND60 exhibited anxiety- but not depression-like behavior. STM but not LTM was impaired. Rats exposed to SPS at PND90 exhibited fearful (as indicated by elevated plus maze test) but not an overall anxiety-like behavior (in light and dark test). These rats also displayed significant depression-like behavior with no changes in STM or LTM. Interestingly, when data was further analyzed, two subsets of PND90 rats exposed to SPS were identified, "susceptible": with depression-like behavior and "resilient": without depression-like behavior. Importantly, while resilient group expressed early signs of anxiety- (at PND32 and PND60) and depression-like behavior (at PND32), these behavioral deficits were absent at PND90. On the other hand, susceptible PND90 rats exposed to SPS expressed later onset of anxiety-like behavior (at PND60), while depression-like phenotype was evident only later on at PND90. CONCLUSIONS: Our findings suggest that early life stress caused co-occurrence of anxiety and depression-like behavior at PND32 (mimics human early-adolescent period). This co-occurrence was lost at PND60 with demonstration of anxiety- but not depression-like behavior. Later, depression but not anxiety-like behavior was observed at PND90. It seems that behavioral adaptations occur at the critical PND60 stage (mimics human late-adolescent period), where behavioral and cognitive switching occurs, thereby, expressing susceptible and resilient phenotypes.

Prior treadmill exercise promotes resilience to vicarious trauma in rats.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a serious psychological condition, which can develop both from physically experiencing and also from witnessing traumatic events. There is evidence that physical exercise can have a positive impact on the symptoms of PTSD. Relevant to this, in our previous pre-clinical work, beneficial effects of treadmill exercise were reported on PTSD-like behaviors in a social defeat paradigm, a rat model of direct physical trauma. However, the role of exercise on vicariously acquired PTSD-like phenotype was not examined. OBJECTIVE: In this study, we utilized a rodent PTSD model, which mimics both the physical as well as the witness experience of trauma, and examined the impact of moderate treadmill exercise in mitigating vicariously acquired PTSD-like behaviors in rats. METHODS: Our PTSD model is a modified social defeat paradigm, which involves aggressive encounters between a large Long-Evans male rat (resident) and a smaller Sprague-Dawley male rat (intruder), resulting in intruder social defeat. The cage mate of the intruder is positioned to witness intruder defeat. Rats were grouped as control (CON), social defeat (SD), exercise (EX), trauma witness (TW), and exercise prior to trauma witness (EX-TW). After acclimatization for 7days, the exercised groups were subjected to a daily 30-min treadmill exercise regimen for 14days. On day 21, the SD group was exposed for 7days of social defeat, while the TW groups witnessed social defeat. On days 28-34, behavioral and cognitive tests including short-term (STM) and long-term (LTM) memory function, anxiety- and depression-like behaviors were conducted. RESULTS: TW and SD rats demonstrated the highest levels of anxiety- and depression-like behaviors, while EX-TW rats did not exhibit anxiety- and depression-like behaviors. TW and SD rats showed no impairments in STM. However, TW and SD rats showed impairments in LTM, and exercise rescued LTM impairments in EX-TW rats. CONCLUSIONS: This study demonstrates that rats subjected to direct experience or witness of social defeat exhibited PTSD-like behaviors, while moderate treadmill exercise prevented trauma witness-induced behavioral impairments. These studies have important translational value suggesting that prior treadmill exercise might provide resilience to stressful stimuli and perhaps mitigate the witnessing effects of traumatic events.

Tempol protects sleep-deprivation induced behavioral deficits in aggressive male Long-Evans rats.

Earlier, we reported that elevated anxiety-like behavior and high aggression in aged retired breeder Long-Evans (L-E) rats was associated with increased plasma corticosterone and elevated oxidative stress levels. In the present study, we examined how this aged aggressive and anxious rat strain responds to acute sleep deprivation (24h) and whether their behaviors can be modulated via antioxidant tempol treatment. Four groups of L-E rats were utilized: naïve control (NC), tempol treated control (T+NC), sleep deprived (SD), tempol treated and sleep deprived (T+SD). Thus, two groups were treated with tempol (1mM in drinking water for 2 weeks) while the other two were not. Two groups were subjected to acute sleep deprivation (24h) using the columns-in-water model while the other two were not. Sleep deprivation induced anxiety-like behavior, led to significant depression-like behavior and short-term memory impairment in SD rats. And, decision-making behavior also was compromised in SD rats. These behavioral and cognitive impairments were prevented with tempol treatment in T+SD rats. Tempol treatment also reduced SD-induced increase in corticosterone and oxidative stress levels in T+SD rats. These results suggest potential involvement of oxidative stress mechanisms in regulation of sleep deprivation induced behavioral and cognitive deficits in male aged-aggressive rats.