Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia/reperfusion injury

Studies have confirmed a strong association between activation of the endoplasmic reticulum stress pathway and cerebral ischemia/reperfusion(I/R) injury.In this study,three key proteins in the endoplasmic reticulum stress pathway(glucose-regulated protein 78,caspase-12,and C/EBP homologous protein) were selected to examine the potential mechanism of endoplasmic reticulum stress in the neuroprotective effect of G protein-coupled estrogen receptor.Female Sprague-Dawley rats received ovariectomy(OVX),and then cerebral I/R rat models(OVX+ I/R) were established by middle cerebral artery occlusion.Immediately after I/R,rat models were injected with 100 μg/kg E2(OVX + I/R +E2),or 100 μg/kg G protein-coupled estrogen receptor agonist G1(OVX + I/R + G1) in the lateral ventricle.Longa scoring was used to detect neurobehavioral changes in each group.Infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride staining.Morphological changes in neurons were observed by Nissl staining.Terminal dexynucleotidyl transferase-mediated nick end-labeling staining revealed that compared with the OVX + I/R group,neurological function was remarkably improved,infarct volume was reduced,number of normal Nissl bodies was dramatically increased,and number of apoptotic neurons in the hippocampus was decreased after E2 and G1 intervention.To detect the expression and distribution of endoplasmic reticulum stress-related proteins in the endoplasmic reticulum,caspase-12 distribution and expression were detected by immunofluorescence,and mRNA and protein levels of glucose-regulated protein 78,caspase-12,and C/EBP homologous protein were determined by polymerase chain reaction and western blot assay.The results showed that compared with the OVX+ I/R group,E2 and G1 treatment obviously decreased mRNA and protein expression levels of glucose-regulated protein 78,C/EBP homologous protein,and caspase-12.However,the G protein-coupled estrogen receptor antagonist G15(OVX + I/R + E2 + G15) could eliminate the effect of E2 on cerebral I/R injury.These results confirm that E2 and G protein-coupled estrogen receptor can inhibit the expression of endoplasmic reticulum stress-related proteins and neuronal apoptosis in the hippocampus,thereby improving dysfunction caused by cerebral I/R injury.Every experimental protocol was approved by the Institutional Ethics Review Board at the First Affiliated Hospital of Shihezi University School of Medicine,China(approval No.SHZ A2017-171) on February 27,2017.

Dip2a regulates stress susceptibility in the basolateral amygdala

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice

Stress has been suggested to disturb the 5-hydroxytryptamine system and decrease neurogenesis, which contribute to the development of depression. Few studies have investigated the effect of predator stress, a type of psychological stress, on depression and hippocampal neurogenesis in adult mice; we therefore investigated this in the present study. A total of 35 adult male Kunming mice were allocated to a cat stress group, cat odor stress group, cat stress + fluoxetine group, cat odor stress + fluoxetine group, or a control group(no stress/treatment). After 12 days of cat stress or cat odor stress, behavioral correlates of depression were measured using the open field test, elevated plus maze test, and dark-avoidance test. The concentrations of hippocampal 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were measured using high-performance liquid chromatography-electrochemical detection. Neurogenesis was also analyzed using a bromodeoxyuridine and doublecortin double-immunostaining method. Cat stress and cat odor stress induced depression-like behaviors; this effect was stronger in the cat stress model. Furthermore, compared with the control group, cat stress mice exhibited lower 5-hydroxytryptamine concentrations, higher 5-hydroxyindoleacetic acid concentrations, and significantly fewer bromodeoxyuridine+/doublecortin+-labeled cells in the dentate gyrus, which was indicative of less neurogenesis. The changes observed in the cat stress group were not seen in the cat stress + fluoxetine group, which suggests that the effects of predator stress on depression and neurogenesis were reversed by fluoxetine. Taken together, our results indicate that depression-like behaviors induced by predator stress are associated with the inhibition of hippocampal neurogenesis.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

Resveratrol reduces brain injury after subarachnoid hemorrhage by inhibiting oxidative stress and endoplasmic reticulum stress

Previous studies have shown that resveratrol,a bioactive substance found in many plants,can reduce early brain injury after subarachnoid hemorrhage,but how it acts is still unclear.This study explored the mechanism using the experimental subarachnoid hemorrhage rat model established by injecting autologous blood into the cerebellomedullary cistern.Rat models were treated with an intraperitoneal injection of 60 mg/kg resveratrol 2,6,24 and 46 hours after injury.At 48 hours after injury,their neurological function was assessed using a modified Garcia score.Brain edema was measured by the wet-dry method.Neuronal apoptosis in the prefrontal cortex was detected by terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay.Levels of reactive oxygen species and malondialdehyde in the prefrontal cortex were determined by colorimetry.CHOP,glucose-regulated protein 78,nuclear factor-erythroid2-related factor 2 and heme oxygenase-1 mRNA expression levels in the prefrontal cortex were measured by reverse transcription polymerase chain reaction.Tumor necrosis factor-alpha content in the prefrontal cortex was detected by enzyme linked immunosorbent assay.Immunohistochemical staining was used to detect the number of positive cells of nuclear factor-erythroid 2-related factor 2,heme oxygenase 1,glucose-regulated protein 78,CHOP and glial fibrillary acidic protein.Western blot assay was utilized to analyze the expression levels of nuclear factor-erythroid 2-related factor 2,heme oxygenase 1,glucose-regulated protein 78 and CHOP protein expression levels in the prefrontal cortex.The results showed that resveratrol treatment markedly alleviated neurological deficits and brain edema in experimental subarachnoid hemorrhage rats,and reduced neuronal apoptosis in the prefrontal cortex.Resveratrol reduced the levels of reactive oxygen species and malondialdehyde,and increased the expression of nuclear factor-erythroid 2-related factor 2,heme oxygenase-1 mRNA and protein in the prefrontal cortex.Resveratrol decreased glucose-regulated protein 78,CHOP mRNA and protein expression and tumor necrosis factor-alpha level.It also activated astrocytes.The results suggest that resveratrol exerted neuroprotective effect on subarachnoid hemorrhage by reducing oxidative damage,endoplasmic reticulum stress and neuroinflammation.The study was approved by the Animals Ethics Committee of Shandong University,China on February 22,2016(approval No.LL-201602022).

Protective effect of hydrogen sulfide on oxidative stress-induced neurodegenerative diseases

Hydrogen sulfide is an antioxidant molecule that has a wide range of biological effects against oxidative stress. Balanced oxidative stress is also vital for maintaining cellular function in biological system, where reactive oxygen species are the main source of oxidative stress. When the normal redox balance is disturbed, deoxyribonucleic acid, lipid, and protein molecules are oxidized under pathological conditions, like diabetes mellitus that leads to diabetic peripheral neuropathy. In diabetes mellitus-induced diabetic peripheral neuropathy, due to hyperglycemia, pancreatic beta cell(β cell) shows resistance to insulin secretion. As a consequence, glucose metabolism is disturbed in neuronal cells which are distracted from providing proper cell signaling pathway. Not only diabetic peripheral neuropathy but also other central damages occur in brain neuropathy. Neurological studies regarding type 1 diabetes mellitus patients with Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis have shown changes in the central nervous system because high blood glucose levels(HbA1 c) appeared with poor cognitive function. Oxidative stress plays a role in inhibiting insulin signaling that is necessary for brain function. Hydrogen sulfide exhibits antioxidant effects against oxidative stress, where cystathionine β synthase, cystathionine γ lyase, and 3-mercaptopyruvate sulfurtransferase are the endogenous sources of hydrogen sulfide. This review is to explore the pathogenesis of diabetes mellitus-induced diabetic peripheral neuropathy and other neurological comorbid disorders under the oxidative stress condition and the anti-oxidative effects of hydrogen sulfide.

Stress-Tolerant Cassava: The Role of Integrative Ecophysiology-Breeding Research in Crop Improvement

This review highlights an integrative multidisciplinary eco-physiological, breeding and agronomical research on the tropical starchy root crop cassava conducted at CIAT. Laboratory and field studies have elucidated several physio-logical/biochemical mechanisms and plant traits underlying the high productivity in favorable conditions and tolerance to stressful environments, such as prolonged water stress and marginal low-fertility soils. Cassava is endowed with inherent high photosynthetic capacity expressed in near optimal environments that correlates with biological produc- tivity across environments and wide range of germplasm.Field-measured photosynthetic rates were also associated with root yield, particularly under prolonged drought. Extensive rooting systems and stomatal sensitivity to both atmospheric humidity and soil water shortages underlie tolerance to drought. The C4 phosphoenolpyruvate carboxylase (PEPC) was associated with photosynthesis and yield making it a selectable trait, along with leaf duration, particularly for stressful environments. Germplasm from the core collection was screened for tolerance to soils low in P and K, resulting in the identification of several accessions with good levels of tolerance. Cassava has a comparative advantage against major tropical food and energy crops in terms of biological productivity. Results also point to the importance of field research versus greenhouse or growth-chamber studies. In globally warming climate,the crop is predicted to play more role in tropical and subtropical agro-ecosystems. More research is needed under tropical field conditions to understand the interactive responses to elevated carbon dioxide, temperature, soil fertility, and plant water relations.

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.

Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis

Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit(ICU). It poses a risk of clinically relevant upper gastrointestinal(GI) bleeding. Therefore, stress ulcer prophylaxis(SUP)is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors(PPI) and, less effectively, histamine 2 receptor antagonists(H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2 RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk-adjusted algorithms, balancing benefits and threats of SUP medication in the ICU.

Aetiology and mechanisms of injury in medial tibial stress syndrome: Current and future developments

Medial tibial stress syndrome(MTSS) is a debilitating overuse injury of the tibia sustained by individuals whoperform recurrent impact exercise such as athletes and military recruits. Characterised by diffuse tibial anteromedial or posteromedial surface subcutaneous periostitis, in most cases it is also an injury involving underlying cortical bone microtrauma, although it is not clear if the soft tissue or cortical bone reaction occurs first. Nuclear bone scans and magnetic resonance imaging(MRI) can both be used for the diagnosis of MTSS, but the patient's history and clinical symptoms need to be considered in conjunction with the imaging findings for a correct interpretation of the results, as both imaging modalities have demonstrated positive findings in the absence of injury. However, MRI is rapidly becoming the preferred imaging modality for the diagnosis of bone stress injuries. It can also be used for the early diagnosis of MTSS, as the developing periosteal oedema can be identified. Retrospective studies have demonstrated that MTSS patients have lower bone mineral density(BMD) at the injury site than exercising controls, and preliminary data indicates the BMD is lower in MTSS subjects than tibial stress fracture(TSF) subjects. The values of a number of tibial geometric parameters such as cross-sectional area and section modulus are also lower in MTSS subjects than exercising controls, but not as low as the values in TSF subjects. Thus, the balance between BMD and cortical bone geometry may predict an individual's likelihood of developing MTSS. However, prospective longitudinal studies are needed to determine how these factors alter during the development of the injury and to find the detailed structural cause, which is still unknown. Finite element analysis has recently been used to examine the mechanisms involved in tibial stress injuries and offer a promising future tool to understand the mechanisms involved in MTSS. Contemporary accurate diagnosis of either MTSS or a TSF includes a thorough clinical examination to identify signs of bone stress injury and to exclude other pathologies. This should be followed by an MRI study of the whole tibia. The cause of the injury should be established and addressed in order tofacilitate healing and prevent future re-occurrence.

Vulnerability and Resilience to Stress and Immune and Neuroendocrine Function in Portuguese Subjects with Psychic Anomaly (Anxiety and Depression)

The present study aimed to investigate the impact of chronic psychosocial stress and resilience, including at a biological level (immune and neuroendocrine function) in Portuguese citizens with psychic anomaly/mental disorder. The sample aggregated 69 participants. It has been used the following psychometric instruments: 21-item depression, anxiety and stress scales (DASS-21), in the Portuguese validated version;measuring state resilience (MSR), in the Portuguese validated version;the Portuguese scale of 23 questions on vulnerability to stress. Serum levels of cortisol, dehydroepiandrosterone sulfate, antibodies anti-viral capsid antigen of Epstein-Barr virus, triglycerides, high density lipoprotein-cholesterol and body mass index have been measured. It has been concluded that factors of vulnerability to stress and chronic stress, of social nature (lack of social support, adverse living conditions), correlate positively with depression, anxiety and stress, and, through alostatic load, are involved in a greater propensity for immune and neuroendocrine dysfunction in this population.

Bilateral sequential femoral neck stress fractures in young adult with HIV infection on antiretroviral therapy: A case report

BACKGROUND Femoral neck stress fractures are rarely encountered among young adults and are often associated with either repetitive excessive loading or underlying bone pathology.Preliminary research has indicated human immunodeficiency virus(HIV)/antiretroviral therapy(ART)as predisposing agents to osteopenia and osteoporosis related complications.We report a case of HIV/ART induced insufficiency fracture in a resource limited setting in Central India.Our aim is to increase awareness and promote screening of HIV/ART related osteopenia and osteoporosis in order to prevent catastrophic orthopaedic complications.CASE SUMMARY A 35-year-old HIV positive male presented with a stress fracture of left femoral neck.The patient was on ART and reported no comorbidities.He went on to be successfully managed surgically.However,during work-up osteopenia of the contralateral proximal femur was recognised using Singh’s Index.Six months post-op the patient presented with right-sided femoral-neck stress fracture.At this stage the patient was nonconcordant with ART and denied surgical fixation.CONCLUSION In the absence of co-morbidities,several mechanisms of HIV/antiretroviral therapy may have played a role in predisposing our patient towards such a presentation.We recommend routine screening all HIV-infected patients for osteopenia,especially in younger individuals.In low resource settings and district hospitals,pelvis radiograph&Singh’s index can be used for screening.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

Intact soft clay’s critical response to dynamic stress paths on different combinations of principal stress orientation

Comprehensive tests on Hangzhou intact soft clay were performed, which were used to obtain the soils' critical response to undrained dynamic stress paths under different combinations of principal stress orientation. The different combinations included cyclic principal stress rotation (CPSR for short), cyclic shear with abrupt change of principal stress orientation (CAPSO for short) and cyclic shear with fixed principal stress orientation (CFPSO for short). On one side, under all these stress paths, samples have obvious strain inflection points and shear bands, and the excess pore water pressure is far from the level of initial effective confining pressure at failure. Stress paths of major principal stress orientation (α) alternating from negative and positive have quite different influence on soil's properties with those in which α is kept negative or positive. On the other side, due to the soil's strongly initial anisotropy, samples under double-amplitudes CPSR and CAPSO (or single-amplitude CPSR and CFPSO) have similar properties on dynamic shear strength and pore water pressure development tendency when α is kept within ±45°, while have quite different properties when α oversteps ±45°.

Dynamic changes of behaviors, dentate gyrus neurogenesis and hippocampal miR-124 expression in rats with depression induced by chronic unpredictable mild stress

The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.

Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcoholinduced oxidative stressed rats

Objective:To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation,changes in catalase activities and hepatic biochemical marker levels in blood plasma.Methods:Oxidative stress was induced by oral administration of ethanol(20%w/v) at a dosage of 5 niL/kg bw in rats.After 28 days of treatment,the rats were fasted overnight and sacrificed by cervical dislocation.Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3000 rpm for 10 min.The plasma was analyzed to evaluate malondialdehyde(MDA),catalase activity,aspartate aminotransferase(AST),alkaline phosphatase(ALP) and alanine aminotransferase(ALT) concentrations.Results:Administration of alcohol caused a drastic increase(87.74%) in MDA level compared with the control.Pineapple peel extract significantly reduced the MDA level by 60.16%at 2.S mL/kg bw.Rats fed alcohol only had the highest catalase activity,treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity.Increased AST,ALP and ALT activities were observed in rats fed alcohol only respectively,treatment with pineapple peel extract drastically reduced their activities. Conclusions:The positive modulation of lipid peroxidation,catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcoholinduced oxidative stress is an indication of its protective ability in the management of alcoholinduced toxicity.

Effects of a Stress Management Program Based on Psychological Risk Factors of Cardiovascular Disease after Retirement in an Underpopulated Area: A Pilot Study

Background: To develop an effective health education program to prevent cardiovascular disease in middle-aged residents after retirement in underpopulated areas, we explored the effects of a stress management program based on the type A behavior pattern. Methods: This study was carried out in a rural city in Japan recognized as underpopulated and participants were civil servants aged 45 - 64 who joined a stress management program offered as part of staff training. Learning materials for the program were developed based on the type A behavior pattern. Measures for the impact evaluation were Bloom’s learning domains and stage of change for stress management practice. Measures for the outcome evaluation were KG’s Daily Life Questionnaire (KG Questionnaire), the Hospital Anxiety and Depression Scale (HADS) and the Framingham 10-year cardiovascular risk score (CVD risk score). We statistically analyzed changes in each item between time points. Results: Eighteen participants completed questionnaire surveys at pre-, post-, and 4 weeks post-program and eleven had complete blood pressure and weight measurements at pre- and post-program. In the impact evaluation, the Friedman test found significant differences between the three time points in all of Bloom’s learning domain scores and stage of change for stress management. In the post hoc analysis, a significant increase was seen between pre- and post-program and between pre- and 4 weeks post-program in cognitive domain score, psychomotor domain score and stage of change for stress management. In the outcome evaluation, a significant decrease in systolic blood pressure was seen between pre- and post-program. Conclusion: The present study suggested that a stress management program using learning materials based on type A behavior could promote stress management practices and reduce the risk of cardiovascular disease. This stress management program is expected to be useful as a health promotion activity for middle-aged residents after retirement in underpopulated areas.

Integrative Modeling of Oxidative Stress and C1 Metabolism Reveals Upregulation of Formaldehyde and Downregulation of Glutathione

This research provides, to the authors’ knowledge, the first integrative model of oxidative stress and C1 metabolism in plants. Increased oxidative stress can cause irreversible damage to photosynthetic components and is harmful to plants. Perturbations at the genetic level may increase oxidative stress and upregulate antioxidant systems in plants. One of the key mechanisms involved in oxidative stress regulation is the ascorbate-glutathione cycle which operates in chloroplasts as well as the mitochondria and is responsible for removal of reactive oxygen species (ROS) generated during photosynthetic operations and respiration. In this research, the complexity of molecular pathway systems of oxidative stress is modeled and then integrated with a previously developed in silico model of C1 metabolism system. This molecular systems integration provides two important results: 1) demonstration of the scalability of the CytoSolve&#174?Collaboratory&#153, a computational systems biology platform that allows for modular integration of molecular pathway models, by coupling the in silico model of oxidative stress with the in silico model of C1 metabolism, and 2) derivation of new insights on the effects of oxidative stress on C1 metabolism relative to formaldehyde (HCHO), a toxic molecule, and glutathione (GSH), an important indicator of oxidative homeostasis in living systems. Previous in silico modeling of C1 metabolism, without oxidative stress, observed complete removal of formaldehyde via formaldehyde detoxification pathway and no change in glutathione concentrations. The results from this research of integrative oxidative stress with C1 metabolism, however, demonstrate significant upregulation of formaldehyde concentrations, with concomitant downregulation and depletion of glutathione. Sensitivity analysis indicates that kGSH-HCHO, the rate constant of GSH-HCHO binding, VSHMT, the rate of formation of sarcosine from glycine, and , the rate of superoxide formation significantly affect formaldehyde homeostasis in the C1 metabolism. Future research may employ this integrative model to explore which conditions initiate oxidative stress and the resultant upregulation and downregulation of formaldehyde and glutathione.

MMPI-2评估应激障碍的效果

目的:采用MMPI-2评估应激障碍(SD)患者的病理心理特征,并探讨其辅助诊断的应用价值。方法:实验组为入院治疗的29名急性应激障碍(ASD)患者及14名创伤后应激障碍(PTSD)患者,对照组为44名适应良好的应激创伤幸存者,在不影响测验症状的情况下完成MMPI-2测试。结果:ASD患者MMPI-2的F、Fb、Fp、Pa、Pt、Sc和Ma的因子得分高于对照组,K和S低于对照组,差异有统计学显著性(P<0.05-0.001);PTSD患者F、Fb、Fp、Hs、D、Hy、Pa、Pt和Sc高于对照组,S低于对照组,差异有统计学显著性(P<0.05-0.001);ASD患者Hs、D和Hy低于PTSD患者,差异有统计学显著性(P<0.05-0.001)。两组患者剖面图均呈M678型。Pa和Sc进入判别函数,该函数在训练样本和验证样本中的预测符合率分别为83.9%和72.0%。结论:SD患者和适应良好的创伤幸存者的心理病理表现明显不同,ASD患者和PTSD患者的症状特征也有所差异;MMPI-2对应激失常症状比较敏感,Pa和Sc具有较好的鉴别能力。