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.

Behavioral and Neuronal Effects of Inhaled Bromine Gas: Oxidative Brain Stem Damage.

The risk of accidental bromine (Br2) exposure to the public has increased due to its enhanced industrial use. Inhaled Br2 damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br2 in Sprague Dawley rats. Rats were exposed to Br2 (600 ppm for 45 min) and transferred to room air and cage behavior, and levels of glial fibrillary acidic protein (GFAP) in plasma were examined at various time intervals. Bromine exposure resulted in abnormal cage behavior such as head hitting, biting and aggression, hypervigilance, and hyperactivity. An increase in plasma GFAP and brain 4-hydroxynonenal (4-HNE) content also was observed in the exposed animals. Acute and delayed sympathetic nervous system activation was also evaluated by assessing the expression of catecholamine biosynthesizing enzymes, tryptophan hydroxylase (TrpH1 and TrpH2), and tyrosine hydroxylase (TyrH), along with an assessment of catecholamines and their metabolites. TyrH was found to be increased in a time-dependent manner. TrpH1 and TrpH2 were significantly decreased upon Br2 exposure in the brainstem. The neurotransmitter content evaluation indicated an increase in 5-HT and dopamine at early timepoints after exposure; however, other metabolites were not significantly altered. Taken together, our results predict brain damage and autonomic dysfunction upon Br2 exposure.

Combined effect of different teaching strategies on student performance in a large-enrollment undergraduate health sciences course.

Students' course performance is fundamental for any institution to carry out its academic mission. Often, in-class disengagement and lack of after-class course support in large-enrollment classes trigger academic problems for students. This leads to poor exam performance and an increased rate of final letter grade of a D or F or student withdrawal (DFW), an indicator of students' poor academic success. Changing teaching strategies by using interventions that incorporate student-student interaction and student-faculty interaction may offer the opportunity to improve course performance. In this retrospective study, we examined the effect of changing teaching strategies on student course performance of 5,553 students enrolled in an undergraduate health sciences course over a span of 20 semesters. Three different interventions namely 1) daily low-stake in-class quizzes, 2) team-based learning, and 3) after-class review sessions were incorporated as teaching strategies. To assess the combined effect of these strategies' students' performance in the intervention period (12 semesters) was compared with control period (8 semesters). Student performance in the course was measured by exam grades; overall score; percentage of students receiving letter grades and A, B, C; and DFW rates. The data indicated that in the intervention period, exam scores increased by 6.6%, overall course score increased by 6.2%, percentage of students receiving letter grade A/B increased by 21.3%, percentage of students receiving letter grade C decreased by 6.9%, and the DFW rates decreased by 14.5%. Overall, changing teaching strategies through incorporation of these interventions improved students' performance in the course.

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.

The Stress of the COVID-19 Pandemic: Beyond the Data.

BACKGROUND: The year 2020 will go down in modern history as the one ravaged by a pandemic, the one which humbled the entire world. From the richest and most advanced nations to the poorest and least developed ones, it exposed all of our vulnerabilities. The loss of life, health disparities and economic adversities, aggravated by political and ideological tensions, added multiple layers of stress and anxieties to an already stressed American society. METHODS: The educational institutions in the United States from the central to the local units demonstrated coherence in leadership, guided with flexibility and compassion, which paved the way for smooth operations. However, anxiety among students and faculty of university and college campuses is undeniable. In-person instruction was halted. Research labs and offices were locked down or operating with limited personnel. Thus, the challenges to have timely instruction and to move the research enterprise forward have been enormous. Provided here is a perspective based on a literature search using PubMed and Google with search words "COVID-19, stress, college students", "COVID-19, stress, US graduate students", and "COVID-19, stress, postdoc researchers". RESULTS: This article is an opinion piece, part personal and part peer experiences. It is presented in light of studies suggesting that the COVID-19 pandemic has imposed significant mental stress and anxiety upon students and faculty members within the academy. CONCLUSION: Loss of face-to-face interactions as a result of virtual instructions, lack of in-person mentoring, and loss of research productivity have affected mental health and well-being of the academic community. Despite the challenges of the pandemic, the ingenuity of the human spirit has innovated solutions to catch up on research productivity and to pursue academic excellence.

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.

Simulated vehicle exhaust exposure (SVEE) in rats impairs renal mitochondrial function.

PURPOSE:  Vehicle exhaust emissions primarily comprise of nitrogen, oxygen, water, CO2, NO2, CO, hydrocarbons and particulate matter. While adverse effects of hydrocarbon and particulate matter on cardiovascular functions are known, the effect of pro-oxidants CO2, NO2 and CO are not clear. METHODS:  Here, using an animal model of a simulated mixture of pro-oxidants (0.04% CO2, 0.9 ppm NO2 and 3 ppm CO with air as a base), we examined the effect of simulated vehicle exhaust exposure (SVEE) on various cardiovascular parameters. Male Sprague-Dawley rats were exposed to SVEE or ambient air (Control: CON) for 30 min/day for 2 weeks. Thereafter, systolic and diastolic blood pressure, heart rate and glomerular filtration rate were measured. Later, rats were sacrificed, blood plasma and kidneys were collected. RESULTS:  The systolic and diastolic blood pressure, heart rate and glomerular filtration rate remained unchanged. Plasma corticosterone increased in SVEE rats when compared to CON group. Plasma 8-isoprostane, a systemic marker of oxidative stress, increased while total antioxidant capacity decreased in SVEE but not in CON. Kidney cortical tissue homogenates exhibited increase in superoxide, hydrogen peroxide and protein carbonylation in SVEE but not CON, all indicative of heightened oxidative stress. Renal cortical mitochondrial SOD activity was significantly reduced in SVEE than CON. CONCLUSION:  Significant decline in mitochondrial respiration and oxygen consumption was observed, in addition to low ATP, reduced ATP synthase and cytochrome C oxidase levels, as well as accelerated mitochondrial fission, and reduced fusion processes, were observed in SVEE than CON rats, all indicative of renal mitochondrial impairment.

Involvement of oxidative stress and mitochondrial mechanisms in air pollution-related neurobiological impairments.

BACKGROUND: Vehicle exhaust emissions are known to be significant contributors to physical and psychological stress. Vehicle exhaust-induced stress and associated respiratory and cardiovascular complications are well-known, but the impact of this stress on the brain is unclear. Simulated vehicle exhaust exposure (SVEE) in rats causes behavioral and cognitive deficits. In the present study, the underlying mechanisms were examined. Our postulation is that SVEE, a simulation of physiologically relevant concentrations of pro-oxidants (0.04% carbon dioxide, 0.9 ppm nitrogen dioxide, 3 ppm carbon monoxide) creates a toxic stress environment in the brain that results in an imbalance between production of reactive oxygen species and the counteracting antioxidant mechanisms. This impairs mitochondrial function in the high bioenergetic demand areas of the brain including the hippocampus (HIP), amygdala (AMY) and the prefrontal cortex (PFC), disrupting neuronal network, and causing behavioral deficits. Mitochondria-targeted antioxidant Mito-Q protects against these impairments. METHODS: Sprague Dawley rats were provided with Mito-Q (250 µM) in drinking water for 4 weeks followed by SVEE 5 h/day for 2 weeks, followed by behavioral and biochemical assessments. RESULTS: SVEE resulted in anxiety- and depression-like behavior, accompanied with increased oxidative stress, diminished antioxidant response and mitochondrial impairment reflected from electron transport chain (ETC) disruption, reduced oxygen consumption, low adenosine tri-phosphate (ATP) synthesis and an alteration in the mitochondrial biochemical dynamics assessed via protein expression profiles of mitochondrial fission marker, dynamin-related protein-1 and fusion markers, mitofusin-1/2 in the HIP, AMY and the PFC. Mito-Q treatment prevented SVEE-induced behavioral deficits, attenuated rise in oxidative stress and also prevented SVEE-induced mitochondrial impairment. CONCLUSION: This study demonstrates a causal mechanism mediating SVEE-induced behavioral deficits in rats. We further established that SVEE is a toxicological stressor that induces oxidative stress and results in mitochondrial impairment, which by disrupting neural circuitry impairs cognitive and behavioral functions.

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.

Neurobehavioral Consequences of Traffic-Related Air Pollution.

Traffic-related air pollution (TRAP) is a major contributor to global air pollution. The World Health Organization (WHO) has reported that air pollution due to gasoline and diesel emissions from internal combustion engines of automobiles, trucks, locomotives, and ships leads to 800,000 premature deaths annually due to pulmonary, cardiovascular, and neurological complications. It has been observed that individuals living and working in areas of heavy vehicle traffic have high susceptibility to anxiety, depression, and cognitive deficits. Information regarding the mechanisms that potentially lead to detrimental mental health effects of TRAP is gradually increasing. Several studies have suggested that TRAP is associated with adverse effects in the central nervous system (CNS), primarily due to increase in oxidative stress and neuroinflammation. Animal studies have provided further useful insights on the deleterious effects of vehicle exhaust emissions (VEEs). The mechanistic basis for these effects is unclear, although gasoline and diesel exhaust-induced neurotoxicity seems the most plausible cause. Several important points emerge from these studies. First, TRAP leads to neurotoxicity. Second, TRAP alters neurobehavioral function. Exactly how that happens remains unclear. This review article will discuss current state of the literature on this subject and potential leads that have surfaced from the preclinical work.

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.