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.

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.

Cross-Site Process Evaluation Results for the Early Childhood Education Center Setting: CORD Study.

Background: The Childhood Obesity Research Demonstration project aimed to deliver evidence-based obesity prevention interventions to at-risk families at three demonstration sites. The interventions were delivered in multiple settings, including early childhood education centers (ECECs), public schools, and primary care clinics. An evaluation center conducted cross-site process, impact, and sustainability evaluations. Results of the cross-site process evaluation for the ECECs will be described. Methods: Reach (proportion of the target population who participated), dose delivered (materials and interventions that were distributed), and fidelity (proportion of planned intervention components delivered) were assessed at two levels (researcher-to-provider and provider-to-family levels). Standardized data forms were completed by research team members at each demonstration site with assistance from the evaluation center. Results: The Childhood Obesity Research Demonstration project reached 5174 children and 390 teachers in 58 ECECs. The centers delivered an average of 3.9 hours of training to teachers. A total of 1382 different types of materials were distributed to providers, and from 1.3 to 4.3 hours of technical support were delivered to centers monthly. For fidelity at the researcher-to-provider level, 49.5% (n = 370) of eligible teachers completed all training sessions. Considerable variations across demonstration sites in reach, dose delivered, and fidelity across were observed. Conclusion: The Childhood Obesity Research Demonstration project reached large numbers of children, families, teachers, and ECECs. Maintaining intervention fidelity while reaching large numbers of at-risk individuals proved to be a challenge.

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.

Evaluating sustainability in the Childhood Obesity Research Demonstration project: the model and process.

BACKGROUND: In the context of health-related interventions, sustainability is the capacity to maintain the changes resulting from the intervention. These can be improved policies, practices or trends intended to improve population health. The Childhood Obesity Research Demonstration (CORD) project was a multi-site, multi-intervention collaboration testing the Obesity Chronic Care Model with interventions for childhood obesity prevention and management. We present the model, definitions and methodology used for the cross-site sustainability evaluation of CORD. METHODS: We applied the Ecologic Model of Obesity to childhood obesity interventions to operationalize four sustainability constructs: replicability, continuation of benefits, institutionalization, and community capacity. We used a triangulation approach and employed mixed methods to assess sustainability constructs at each level of the Ecologic Model of Obesity: Micro, Meso, Exo and Macro. We constructed checklists to count and code intervention activities, use of evidence-based practices among providers, and environmental factors and policies hypothesized to influence intervention sustainability. We developed in-depth interviews for principal investigators and project leads. We applied the Wilder Collaboration Factors Inventory with key stakeholders. RESULTS: Lessons learned suggested that sustainability constructs should be clearly identified and operationalized a priori. Constructs must be flexible to account for differences between intervention plans and implementation to obtain robust and informative data. CONCLUSION: Strong links are needed among researchers, program implementers and communities to accomplish consistent, robust and valuable data collection efforts to assure sustainable and healthy communities.

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.

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.