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Sample records for stress-induced glutamate signaling-associated

  1. The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond.

    Science.gov (United States)

    Conrad, Marcus; Sato, Hideyo

    2012-01-01

    The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.

  2. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    Science.gov (United States)

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  3. The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

    Science.gov (United States)

    Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

    2016-04-01

    Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS. Copyright © 2016 the American Physiological Society.

  4. Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

    Science.gov (United States)

    Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

    2015-08-20

    Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

  5. Resolving the Role of Plant NAD-Glutamate Dehydrogenase: III. Overexpressing Individually or Simultaneously the Two Enzyme Subunits Under Salt Stress Induces Changes in the Leaf Metabolic Profile and Increases Plant Biomass Production.

    Science.gov (United States)

    Tercé-Laforgue, Thérèse; Clément, Gilles; Marchi, Laura; Restivo, Francesco M; Lea, Peter J; Hirel, Bertrand

    2015-10-01

    NAD-dependent glutamate dehydrogenase (NAD-GDH) of higher plants has a central position at the interface between carbon and nitrogen metabolism due to its ability to carry out the deamination of glutamate. In order to obtain a better understanding of the physiological function of NAD-GDH under salt stress conditions, transgenic tobacco (Nicotiana tabacum L.) plants that overexpress two genes from Nicotiana plumbaginifolia individually (GDHA and GDHB) or simultaneously (GDHA/B) were grown in the presence of 50 mM NaCl. In the different GDH overexpressors, the NaCl treatment induced an additional increase in GDH enzyme activity, indicating that a post-transcriptional mechanism regulates the final enzyme activity under salt stress conditions. A greater shoot and root biomass production was observed in the three types of GDH overexpressors following growth in 50 mM NaCl, when compared with the untransformed plants subjected to the same salinity stress. Changes in metabolites representative of the plant carbon and nitrogen status were also observed. They were mainly characterized by an increased amount of starch present in the leaves of the GDH overexpressors as compared with the wild type when plants were grown in 50 mM NaCl. Metabolomic analysis revealed that overexpressing the two genes GDHA and GDHB, individually or simultaneously, induced a differential accumulation of several carbon- and nitrogen-containing molecules involved in a variety of metabolic, developmental and stress-responsive processes. An accumulation of digalactosylglycerol, erythronate and porphyrin was found in the GDHA, GDHB and GDHA/B overexpressors, suggesting that these molecules could contribute to the improved performance of the transgenic plants under salinity stress conditions. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

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    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  7. Stress induced reorientation of vanadium hydride

    International Nuclear Information System (INIS)

    Beardsley, M.B.

    1977-10-01

    The critical stress for the reorientation of vanadium hydride was determined for the temperature range 180 0 to 280 0 K using flat tensile samples containing 50 to 500 ppM hydrogen by weight. The critical stress was observed to vary from a half to a third of the macroscopic yield stress of pure vanadium over the temperature range. The vanadium hydride could not be stress induced to precipitate above its stress-free precipitation temperature by uniaxial tensile stresses or triaxial tensile stresses induced by a notch

  8. Cholinergic Modulation of Restraint Stress Induced Neurobehavioral ...

    African Journals Online (AJOL)

    The involvement of the cholinergic system in restraint stress induced neurobehavioral alterations was investigated in rodents using the hole board, elevated plus maze, the open field and the light and dark box tests. Restraint stress (3h) reduced significantly (p<0.05) the number of entries and time spent in the open arm, ...

  9. [Stress-induced cellular adaptive mutagenesis].

    Science.gov (United States)

    Zhu, Linjiang; Li, Qi

    2014-04-01

    The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

  10. Central mechanisms of stress-induced headache.

    Science.gov (United States)

    Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

    2010-03-01

    Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

  11. Cold stress induces lower urinary tract symptoms.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Nishizawa, Osamu

    2013-07-01

    Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 ± 2°C) to low temperature (4 ± 2°C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving α1-adrenergic receptors. Transient receptor potential melastatin 8 channels, which are sensitive to thermal changes below 25-28°C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that α1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs. © 2013 The Japanese Urological Association.

  12. Fabrication of Implantable, Enzyme-Immobilized Glutamate Sensors for the Monitoring of Glutamate Concentration Changes in Vitro and in Vivo

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    Tina T.-C. Tseng

    2014-06-01

    Full Text Available Glutamate sensors based on the immobilization of glutamate oxidase (GlutOx were prepared by adsorption on electrodeposited chitosan (Method 1 and by crosslinking with glutaraldehyde (Method 2 on micromachined platinum microelectrodes. It was observed that glutamate sensors prepared by Method 1 have faster response time (<2 s and lower detection limit (2.5 ± 1.1 μM compared to that prepared by Method 2 (response time: <5 sec and detection limit: 6.5 ± 1.7 μM; glutamate sensors prepared by Method 2 have a larger linear detection range (20–352 μM and higher sensitivity (86.8 ± 8.8 nA·μM−1·cm−2, N = 12 compared to those prepared by Method 1 (linear detection range: 20–217 μM and sensitivity: 34.9 ± 4.8 nA·μM−1·cm−2, N = 8. The applicability of the glutamate sensors in vivo was also demonstrated. The glutamate sensors were implanted into the rat brain to monitor the stress-induced extracellular glutamate release in the hypothalamus of the awake, freely moving rat.

  13. Heat stress induced changes in metabolic regulators of donkeys from arid tracts in India

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    Kataria N.

    2012-05-01

    Full Text Available To find out heat stress induced changes in metabolic regulators of donkeys from arid tracts in India, blood samples were collected to harvest the serum during moderate and extreme hot ambiences. The metabolic enzymes determined were sorbitol dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, ornithine carbamoyl transferase, gammaglutamayl transferase, 5’nucleotidase, glucose-6-phosphatase, arginase, and aldolase. The mean values of all the serum enzymes increased significantly (p≤0.05 during hot ambience as compared to respective values during moderate ambience. It was concluded that increased activity of all the enzymes in the serum was due to modulation of metabolic reactions to combat the effect of hot ambience on the animals. Activation of gluconeogenesis along with hexose monophosphate shunt and urea cycle probably helped the animals to combat the heat stress.

  14. Finite element calculation of stress induced heating of superconductors

    International Nuclear Information System (INIS)

    Akin, J.E.; Moazed, A.

    1976-01-01

    This research is concerned with the calculation of the amount of heat generated due to the development of mechanical stresses in superconducting composites. An emperical equation is used to define the amount of stress-induced heat generation per unit volume. The equation relates the maximum applied stress and the experimental measured hysteresis loop of the composite stress-strain diagram. It is utilized in a finite element program to calculate the total stress-induced heat generation for the superconductor. An example analysis of a solenoid indicates that the stress-induced heating can be of the same order of magnitude as eddy current effects

  15. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

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    Laura Musazzi

    2010-01-01

    Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

  16. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... the swim stress-induced OT response. CONCLUSION: 5-HT(2A), 5-HT(2C) and possibly 5-HT(3) and 5-HT(4) receptors, but not 5-HT(1A) receptors, are involved in the restraint stress-induced AVP secretion. 5-HT does not seem to be involved in the dehydration- or hemorrhage-induced AVP response. The restraint...... stress-induced OT response seems to be mediated via 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors. The dehydration and hemorrhage-induced OT responses are at least mediated by the 5-HT(2A) and 5-HT(2C) receptors. The 5-HT(3) and 5-HT(4) receptors are not involved in stress-induced OT secretion....

  17. Glutamate and Neurodegenerative Disease

    Science.gov (United States)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

  18. Oxidative Stress-Induced Dysfunction of Muller Cells During Starvation

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Gurubaran, Iswariyaraja Sridevi; Madsen, Claus Desler

    2016-01-01

    starvation for 24 hours. Effects of starvation and H2O2 on glutamate uptake and mitochondrial function were assessed by kinetic glutamate uptake assays and Seahorse assays, respectively. Cell survival was evaluated by cell viability assays. mRNA and protein expressions were assessed by quantitative PCR...

  19. Salt stress induced ion accumulation, ion homeostasis, membrane ...

    African Journals Online (AJOL)

    Salt stress induced ion accumulation, ion homeostasis, membrane injury and sugar contents in salt-sensitive rice ( Oryza sativa L. spp. indica ) roots under isoosmotic conditions. ... The accumulation of sugars in PT1 roots may be a primary salt-defense mechanism and may function as an osmotic control. Key words: ...

  20. Implication of snail in metabolic stress-induced necrosis.

    Directory of Open Access Journals (Sweden)

    Cho Hee Kim

    2011-03-01

    Full Text Available Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

  1. Stress-induced hyperthermia in translational stress research

    NARCIS (Netherlands)

    Vinkers, C.H.; Penning, R.; Ebbens, M.M.; Helhammer, J.; Verster, J.C.; Kalkman, C.J.; Olivier, B.

    2010-01-01

    The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in

  2. Salubrious effects of oxytocin on social stress-induced deficits

    Science.gov (United States)

    Smith, Adam S.; Wang, Zuoxin

    2012-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

  3. Water stress induced changes in antioxidant enzymes, membrane ...

    African Journals Online (AJOL)

    Water stress induced changes in antioxidant enzymes membrane stablity index and seed protein profiling of four different wheat (Triticum aestivum L.) accessions (011251, 011417, 011320 and 011393) were determined in a pot study under natural condition during the wheat-growing season 2005 and 2006. Sampling was ...

  4. Identification of salt-stress induced differentially expressed genes in ...

    African Journals Online (AJOL)

    Identification of salt-stress induced differentially expressed genes in barley leaves using the annealingcontrol- primer-based GeneFishing technique. S Lee, K Lee, K Kim, GJ Choi, SH Yoon, HC Ji, S Seo, YC Lim, N Ahsan ...

  5. Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Ying [Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Ziwei [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Tan, Min [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Department of Traditional Chinese Medicine Chemistry, College of Chinese Materia Madica, Guangzhou University of Chinese Medicine, Guangzhou 510006 (China); Liu, Anmin [Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Meihui [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Liu, Jun [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Pi, Rongbiao, E-mail: pirb@mail.sysu.edu.cn [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Fang, Jianpei, E-mail: jpf2005@163.com [Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China)

    2013-11-29

    Highlights: •Carvedilol significantly prevented oxidative stress-induced cell death. •Carvedilol significantly decreased the production of ROS. •Carvedilol activated Nrf2/ARE pathway. •Carvedilol increased the protein levels of HO-1 and NQO-1. -- Abstract: Carvedilol, a nonselective β-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2 mM and H{sub 2}O{sub 2} 600 μM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H{sub 2}O{sub 2}. Furthermore, carvedilol activated the Nrf2/ARE pathway in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H{sub 2}O{sub 2}-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway.

  6. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  7. Evaluation of cytotoxicity and oxidative stress induced by alcoholic ...

    African Journals Online (AJOL)

    Maqsood

    (Duke et al., 1992), sinapic acid and sinapin (Schultz and. Gmelin, 1952), and ... serum glutamic pyruvate transaminase (SGPT) were within normal levels ..... like asthma, skin disease and diabetes (Gill and Macleod, 1980; Maier et al., 1998).

  8. Stress-Induced Enhancement of the Startle Reflex

    National Research Council Canada - National Science Library

    Davis, Michael

    1997-01-01

    A major goal of the work currently funded by the AFOSR is to determine to role of glutamate receptors in the amygdala in conditioned fear and to begin to determine brain areas involved in the inhibition of fear...

  9. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    DEFF Research Database (Denmark)

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...

  10. N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish.

    Science.gov (United States)

    Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L

    2015-12-01

    Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Stress-Induced Visceral Pain: Toward Animal Models of Irritable-Bowel Syndrome and Associated Comorbidities

    Science.gov (United States)

    Moloney, Rachel D.; O’Mahony, Siobhain M.; Dinan, Timothy G.; Cryan, John F.

    2015-01-01

    Visceral pain is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. It is a hallmark of functional gastrointestinal disorders such as irritable-bowel syndrome (IBS). Currently, the treatment strategies targeting visceral pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here, we discuss the complex etiology of visceral pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore, we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of visceral pain for which there is an unmet medical need. Moreover, we discuss the most widely described rodent models used to model visceral pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced visceral pain and its psychiatric comorbidities, as typified by IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far behind when compared to other pain modalities. The development of novel, effective, and specific therapeutics for the treatment of visceral pain has never been more pertinent. PMID:25762939

  12. Social factors modulate restraint stress induced hyperthermia in mice.

    Science.gov (United States)

    Watanabe, Shigeru

    2015-10-22

    Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage

    International Nuclear Information System (INIS)

    Kim, Kyung-A; Shim, Sang Hee; Ahn, Hong Ryul; Jung, Sang Hoon

    2013-01-01

    The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with L-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca 2+ was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-D-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7 days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage, and may be considered as an agent for treating or preventing retinal degeneration. - Highlights: • Psoralea corylifolia have neuroprotective effects in vitro and in vivo. • Bakuchiol attenuated the increase of apoptotic proteins induced by oxidative

  14. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-A [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Shim, Sang Hee [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Ahn, Hong Ryul [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Jung, Sang Hoon, E-mail: shjung507@gmail.com [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of)

    2013-06-01

    The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with L-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca{sup 2+} was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-D-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7 days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage, and may be considered as an agent for treating or preventing retinal degeneration. - Highlights: • Psoralea corylifolia have neuroprotective effects in vitro and in vivo. • Bakuchiol attenuated the increase of apoptotic proteins induced by oxidative

  15. Salubrious effects of oxytocin on social stress-induced deficits

    OpenAIRE

    Smith, Adam S.; Wang, Zuoxin

    2011-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to m...

  16. Environmental stress induces trinucleotide repeat mutagenesis in human cells.

    Science.gov (United States)

    Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

    2015-03-24

    The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

  17. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

    Science.gov (United States)

    Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro

    2016-10-01

    Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  19. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    The brain is reportedly sensitive to monosodium glutamate (MSG) toxicity via oxidative stress. Sida acuta leaf ethanolic .... wherein the right hemisphere, was preserved for histology and fixed in 10% ... Biochemical Assays: The left hemisphere of the brain samples was ...... development in male and female rats. Exp Physiol.

  20. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases

    DEFF Research Database (Denmark)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura Frendrup

    2016-01-01

    to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes...... the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [15N]glutamate demonstrated activity of GDH......The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate–glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back...

  1. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Directory of Open Access Journals (Sweden)

    Beverley Greenwood-Van Meerveld

    2017-11-01

    Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

  2. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

    2017-01-01

    Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced

  3. Lateral stress-induced propagation characteristics in photonic crystal fibres

    Institute of Scientific and Technical Information of China (English)

    Tian Hong-Da; Yu Zhong-Yuan; Han Li-Hong; Liu Yu-Min

    2009-01-01

    Using the finite element method, this paper investigates lateral stress-induced propagation characteristics in a pho-tonic crystal fibre of hexagonal symmetry. The results of simulation show the strong stress dependence of effective index of the fundamental guided mode, phase modal birefringence and confinement loss. It also finds that the contribution of the geometrical effect that is related only to deformation of the photonic crystal fibre and the stress-related contribution to phase modal birefringence and confinement loss are entirely different. Furthermore, polarization-dependent stress sensitivity of confinement loss is proposed in this paper.

  4. Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo

    Directory of Open Access Journals (Sweden)

    Nigel T. Maidment

    2008-08-01

    Full Text Available Using Micro-Electro-Mechanical-Systems (MEMS technologies, we have developed silicon wafer-based platinum microelectrode arrays (MEAs modified with glutamate oxidase (GluOx for electroenzymatic detection of glutamate in vivo. These MEAs were designed to have optimal spatial resolution for in vivo recordings. Selective detection of glutamate in the presence of the electroactive interferents, dopamine and ascorbic acid, was attained by deposition of polypyrrole and Nafion. The sensors responded to glutamate with a limit of detection under 1μM and a sub-1-second response time in solution. In addition to extensive in vitro characterization, the utility of these MEA glutamate biosensors was also established in vivo. In the anesthetized rat, these MEA glutamate biosensors were used for detection of cortically-evoked glutamate release in the ventral striatum. The MEA biosensors also were applied to the detection of stress-induced glutamate release in the dorsal striatum of the freely-moving rat.

  5. Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis

    International Nuclear Information System (INIS)

    Li Tie; Lu Luo

    2007-01-01

    CTCF, a nuclear transcriptional factor, is a multifunctional protein and involves regulation of growth factor- and cytokine-induced cell proliferation/differentiation. In the present study, we investigated the role of CTCF in protecting stress-induced apoptosis in various human cell types. We found that UV irradiation and hyper-osmotic stress induced human corneal epithelial (HCE) and hematopoietic myeloid cell apoptosis detected by significantly increased caspase 3 activity and decreased cell viability. The stress-induced apoptotic response in these cells requires down-regulation of CTCF at both mRNA and protein levels, suggesting that CTCF may play an important role in downstream events of stress-induced signaling pathways. Inhibition of NFκB activity prevented stress-induced down-regulation of CTCF and increased cell viability against stress-induced apoptosis. The anti-apoptotic effect of CTCF was further studied by manipulating CTCF activities in HCE and hematopoietic cells. Transient transfection of cDNAs encoding full-length human CTCF markedly suppressed stress-induced apoptosis in these cells. In contrast, knocking down of CTCF mRNA using siRNA specific to CTCF significantly promoted stress-induced apoptosis. Thus, our results reveal that CTCF is a down stream target of stress-induced signaling cascades and it plays a significant anti-apoptotic role in regulation of stress-induced cellular responses in HCE and hematopoietic myeloid cells

  6. Neuroendocrine and oxidoreductive mechanisms of stress-induced cardiovascular diseases.

    Science.gov (United States)

    Pajović, S B; Radojcić, M B; Kanazir, D T

    2008-01-01

    The review concerns a number of basic molecular pathways that play a crucial role in perception, transmission, and modulation of the stress signals, and mediate the adaptation of the vital processes in the cardiovascular system (CVS). These highly complex systems for intracellular transfer of information include stress hormones and their receptors, stress-activated phosphoprotein kinases, stress-activated heat shock proteins, and antioxidant enzymes maintaining oxidoreductive homeostasis of the CVS. Failure to compensate for the deleterious effects of stress may result in the development of different pathophysiological states of the CVS, such as ischemia, hypertension, atherosclerosis and infarction. Stress-induced dysbalance in each of the CVS molecular signaling systems and their contribution to the CVS malfunctioning is reviewed. The general picture of the molecular mechanisms of the stress-induced pathophysiology in the CVS pointed out the importance of stress duration and intensity as etiological factors, and suggested that future studies should be complemented by the careful insights into the individual factors of susceptibility to stress, prophylactic effects of 'healthy' life styles and beneficial action of antioxidant-rich nutrition.

  7. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  8. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders.

    Science.gov (United States)

    Gu, Simeng; Wang, Wei; Wang, Fushun; Huang, Jason H

    2016-01-01

    Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the central "stress circuitry," whose major function is to induce "fight or flight" behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty). The reason for this discrepancy might be that NE is not only for flight (fear), but also for fight (anger). Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. "Adrenaline rush or norepinephrine rush" and fear and anger emotion might act as biomarkers for mental disorders.

  9. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders

    Directory of Open Access Journals (Sweden)

    Simeng Gu

    2016-01-01

    Full Text Available Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC/norepinephrine (NE system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty. The reason for this discrepancy might be that NE is not only for flight (fear, but also for fight (anger. Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders.

  10. Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

    Science.gov (United States)

    Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

    2014-10-08

    Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

  11. Blood Glutamate Scavenging: Insight into Neuroprotection

    Directory of Open Access Journals (Sweden)

    Alexander Zlotnik

    2012-08-01

    Full Text Available Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

  12. Stress-induced roughening instabilities along surfaces of piezoelectric materials

    International Nuclear Information System (INIS)

    Chien, N.Y.; Gao, H.

    1993-01-01

    The possibility of using electric field to stabilize surfaces of piezoelectric solids against stress-induced morphological roughening is explored in this paper. Two types of idealized boundary conditions are considered: (1) a traction free and electrically insulating surface and (2) a traction free and electrically conducting surface. A perturbation solution for the energy variation associated with surface roughening suggests that the electric field can be used to suppress the roughening instability to various degrees. A completely stable state is possible in the insulating case, and kinetically more stable states can be attained in the conducting case. The stabilization has importance in reducing concentration of stress and electric fields due to microscopic surface roughness which might trigger failure processes involving dislocation, cracks and dielectric breakdown

  13. Stress-induced premature senescence of endothelial cells.

    Science.gov (United States)

    Chen, Jun; Patschan, Susann; Goligorsky, Michael S

    2008-01-01

    Stress-induced premature senescence (SIPS) is characterized by cell cycle arrest and curtailed Hayflick limit. Studies support a central role for Rb protein in controlling this process via signaling from the p53 and p16 pathways. Cellular senescence is considered an essential contributor to the aging process and has been shown to be an important tumor suppression mechanism. In addition, emerging evidence suggests that SIPS may be involved in the pathogenesis of chronic human diseases. Here, focusing on endothelial cells, we discuss recent advances in our understanding of SIPS and the pathways that trigger it, evaluate their correlation with the apoptotic response and examine their links to the development of chronic diseases, with the emphasis on vasculopathy. Emerging novel therapeutic interventions based on recent experimental findings are also reviewed.

  14. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    International Nuclear Information System (INIS)

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

    2014-01-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic

  15. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  16. STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

    Directory of Open Access Journals (Sweden)

    Zachary Robert Patterson

    2013-07-01

    Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress-induced

  17. Clonidine blocks stress-induced craving in cocaine users.

    Science.gov (United States)

    Jobes, Michelle L; Ghitza, Udi E; Epstein, David H; Phillips, Karran A; Heishman, Stephen J; Preston, Kenzie L

    2011-11-01

    Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

  18. Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

    Science.gov (United States)

    Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

    2016-09-01

    Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

  19. The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    M. M. Menezes

    2013-01-01

    Full Text Available Metabotropic glutamate 2/3 (mGlu2/3 receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL and infralimbic (IL cortex. LY354740 (10 and 30 mg/kg, i.p. showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.. Because both compounds inhibit serotonin 2A receptor (5-HT2AR-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

  20. Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tokuda, Kazuhiro, E-mail: r502um@yamaguchi-u.ac.jp [Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Kuramitsu, Yasuhiro; Byron, Baron; Kitagawa, Takao [Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Tokuda, Nobuko [Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube (Japan); Kobayashi, Daiki; Nagayama, Megumi; Araki, Norie [Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Sonoda, Koh-Hei [Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Nakamura, Kazuyuki [Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan)

    2015-08-07

    Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage. Immunohistological evaluations and immunoblotting confirmed the emergence of neuronal progenitor cells in the mature retina treated with glutamate. Proteomic analysis revealed the up-regulation of dihydropyrimidinase-related protein 3 (DRP-3), DRP-2 and stress-induced-phosphoprotein 1 (STIP1) during neural progenitor cell induction by glutamate. Moreover, mRNA expression of DRP-3, especially, its long isoform, robustly increased in the treated retina compared to that in the untreated retina. These results may indicate that glutamate induces neural progenitor cells in the mature rat retina by up-regulating the proteins which mediate cell mitosis and neurite growth. - Highlights: • Glutamate induced neuronal progenitor cells in the mature rat retina. • Proteomic analysis revealed the up-regulation of DRP-3, DRP-2 and STIP1. • mRNA expression of DRP-3, especially, its long isoform, robustly increased.

  1. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  2. Glutamate mechanisms underlying opiate memories

    NARCIS (Netherlands)

    Peters, J.; de Vries, T.J.

    2012-01-01

    As the major excitatory neurotransmitter in the brain, glutamate plays an undisputable integral role in opiate addiction. This relates, in part, to the fact that addiction is a disorder of learning and memory, and glutamate is required for most types of memory formation. As opiate addiction

  3. Stress-induced variation in evolution: from behavioural plasticity to genetic assimilation.

    Science.gov (United States)

    Badyaev, Alexander V

    2005-05-07

    Extreme environments are closely associated with phenotypic evolution, yet the mechanisms behind this relationship are poorly understood. Several themes and approaches in recent studies significantly further our understanding of the importance that stress-induced variation plays in evolution. First, stressful environments modify (and often reduce) the integration of neuroendocrinological, morphological and behavioural regulatory systems. Second, such reduced integration and subsequent accommodation of stress-induced variation by developmental systems enables organismal 'memory' of a stressful event as well as phenotypic and genetic assimilation of the response to a stressor. Third, in complex functional systems, a stress-induced increase in phenotypic and genetic variance is often directional, channelled by existing ontogenetic pathways. This accounts for similarity among individuals in stress-induced changes and thus significantly facilitates the rate of adaptive evolution. Fourth, accumulation of phenotypically neutral genetic variation might be a common property of locally adapted and complex organismal systems, and extreme environments facilitate the phenotypic expression of this variance. Finally, stress-induced effects and stress-resistance strategies often persist for several generations through maternal, ecological and cultural inheritance. These transgenerational effects, along with both the complexity of developmental systems and stressor recurrence, might facilitate genetic assimilation of stress-induced effects. Accumulation of phenotypically neutral genetic variance by developmental systems and phenotypic accommodation of stress-induced effects, together with the inheritance of stress-induced modifications, ensure the evolutionary persistence of stress-response strategies and provide a link between individual adaptability and evolutionary adaptation.

  4. Oxidative Stress Induces Senescence in Cultured RPE Cells.

    Science.gov (United States)

    Aryan, Nona; Betts-Obregon, Brandi S; Perry, George; Tsin, Andrew T

    2016-01-01

    The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period [at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide]. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, cells with a high level of positive senescence-indicator SA-Beta-Gal-positive staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 MCM and at 800 MCM). Our data suggests that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence.

  5. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Gharib Ola

    2009-11-01

    Full Text Available Abstract Background Trichloroethylene (TCE may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1 the control group treated with vehicle, (2 Kombucha (KT-treated group, (3 TCE-treated group and (4 KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT and lactate dehydrogenase (LDH activities were also measured. Results TCE administration increased the malondiahyde (MDA and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  6. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats.

    Science.gov (United States)

    Gharib, Ola Ali

    2009-11-27

    Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  7. Stress-induced hyperglycaemia and venous thromboembolism following total hip or total knee arthroplasty Analysis from the RECORD trials

    NARCIS (Netherlands)

    Cohn, Danny M.; Hermanides, Jeroen; DeVries, J. Hans; Kamphuisen, Pieter-Willem; Kuhls, Silvia; Homering, Martin; Hoekstra, Joost B. L.; Lensing, Anthonie W. A.; Büller, Harry R.

    2012-01-01

    Stress-induced hyperglycaemia is common during orthopaedic surgery. In addition, hyperglycaemia activates coagulation. The aim of the study was to assess whether stress-induced hyperglycaemia is associated with symptomatic or asymptomatic venous thromboembolism (VTE) following orthopaedic surgery.

  8. Effect of chronic mild stress on hippocampal transcriptome in mice selected for high and low stress-induced analgesia and displaying different emotional behaviors.

    Science.gov (United States)

    Lisowski, Pawel; Juszczak, Grzegorz R; Goscik, Joanna; Wieczorek, Marek; Zwierzchowski, Lech; Swiergiel, Artur H

    2011-01-01

    There is increasing evidence that mood disorders may derive from the impact of environmental pressure on genetically susceptible individuals. Stress-induced hippocampal plasticity has been implicated in depression. We studied hippocampal transcriptomes in strains of mice that display high (HA) and low (LA) swim stress-induced analgesia and that differ in emotional behaviors and responses to different classes of antidepressants. Chronic mild stress (CMS) affected expression of a number of genes common for both strains. CMS also produced strain specific changes in expression suggesting that hippocampal responses to stress depend on genotype. Considerably larger number of genes, biological processes, molecular functions, biochemical pathways, and gene networks were affected by CMS in LA than in HA mice. The results suggest that potential drug targets against detrimental effects of stress include glutamate transporters, and cholinergic, cholecystokinin (CCK), glucocorticoids, and thyroid hormones receptors. Furthermore, some biological processes evoked by stress and different between the strains, such as apoptosis, neurogenesis and chromatin modifications, may be responsible for the long-term, irreversible effects of stress and suggest a role for epigenetic regulation of mood related stress responses. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  9. Stress-induced core temperature changes in pigeons (Columba livia).

    Science.gov (United States)

    Bittencourt, Myla de Aguiar; Melleu, Fernando Falkenburger; Marino-Neto, José

    2015-02-01

    Changes in body temperature are significant physiological consequences of stressful stimuli in mammals and birds. Pigeons (Columba livia) prosper in (potentially) stressful urban environments and are common subjects in neurobehavioral studies; however, the thermal responses to stress stimuli by pigeons are poorly known. Here, we describe acute changes in the telemetrically recorded celomatic (core) temperature (Tc) in pigeons given a variety of potentially stressful stimuli, including transfer to a novel cage (ExC) leading to visual isolation from conspecifics, the presence of the experimenter (ExpR), gentle handling (H), sham intracelomatic injections (SI), and the induction of the tonic immobility (TI) response. Transfer to the ExC cage provoked short-lived hyperthermia (10-20 min) followed by a long-lasting and substantial decrease in Tc, which returned to baseline levels 2 h after the start of the test. After a 2-hour stay in the ExC, the other potentially stressful stimuli evoked only weak, marginally significant hyperthermic (ExpR, IT) or hypothermic (SI) responses. Stimuli delivered 26 h after transfer to the ExC induced definite and intense increases in Tc (ExpR, H) or hypothermic responses (SI). These Tc changes appear to be unrelated to modifications in general activity (as measured via telemetrically recorded actimetric data). Repeated testing failed to affect the hypothermic responses to the transference to the ExC, even after nine trials and at 1- or 8-day intervals, suggesting that the social (visual) isolation from conspecifics may be a strong and poorly controllable stimulus in this species. The present data indicated that stress-induced changes in Tc may be a consistent and reliable physiological parameter of stress but that they may also show stressor type-, direction- and species-specific attributes. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Pharmacologic stress-induced stunning: evaluation with quantitative gated SPECT

    International Nuclear Information System (INIS)

    Chun, K. A.; Cho, I. H.; Won, K. J.; Lee, H. W.

    2000-01-01

    The after-effect of pharmacologic stress (adenosine) on left ventricular (LV) function, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were evaluated after pharmacologic stress with Tl-201 and 99m Tc-MIBI SPECT using an automated program in 153 subjects. The subjects were grouped as follows: 1) Tl-201 group (n=35, male 18, female 17, mean age: 58 years); normal scan (n=24), ischemia (n=8) and infarction (n=3). 2) 99m Tc-MIBI group (n=118, male 60, female 58, mean age: 62 years); normal scan (n=73), ischemia (n=20) and infarction (n=25) based on the interpretation of perfusion images. All patients were in sinus rhythm during the study. 1)Tl-201 group; In patients with ischemia (the mean time interval between injection and acquisition is 12.3 min), post-stress LVEF was significantly depressed after adenosine infusion (51.2 ± 6.3% vs 59.8± 8.2%, p 99m Tc-MIBI group; In patients with ischemia (the mean time interval between injection and acquisition is 80 min), post-stress LVEF was significantly depressed after adenosine infusion (p<0.001) and ΔLVEF was 5.1%. Eight patients (40%) showed an increase in LVEF greater than 5% from poststress to rest. Poststress ESV (37.1±17.3 ml) was significantly higher than ESV (31.3±15.5 ml, p<0.001) at rest, but no significant difference in EDV. These results showed that pharmacologic stress induced stunning is well noted in the early quantitative gated SPECT in ischemic patients and also observed in the delayed gated SPECT, even though the rate of stunning is less than the early SPECT

  11. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  12. Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

    Science.gov (United States)

    Yosef, Ido; Edgar, Rotem; Qimron, Udi

    2016-11-01

    Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

  13. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    -500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  14. Circadian Regulation of Glutamate Transporters

    Directory of Open Access Journals (Sweden)

    Donají Chi-Castañeda

    2018-06-01

    Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

  15. Chronic stress-induced effects of corticosterone on brain: direct and indirect

    NARCIS (Netherlands)

    Dallman, M. F.; Akana, S. F.; Strack, A. M.; Scribner, K. S.; Pecoraro, N.; La Fleur, S. E.; Houshyar, H.; Gomez, F.

    2004-01-01

    Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their actions in brain and anterior pituitary (canonical feedback). With chronic stress, glucocorticoid feedback inhibition of ACTH secretion changes

  16. Physiological correlates of stress-induced decrements in human perceptual performance.

    Science.gov (United States)

    1993-11-01

    Stress-induced changes in human performance have been thought to result from alterations in the "multidimensional arousal state" of the individual, as indexed by alterations in the physiological and psychological mechanisms controlling performance. I...

  17. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    OpenAIRE

    Ayşin Akıncı; Mukaddes Eşrefoğlu; Elif Taşlıdere; Burhan Ateş

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino...

  18. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    OpenAIRE

    Ak?nc?, Ay?in; E?refo?lu, Mukaddes; Ta?l?dere, Elif; Ate?, Burhan

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation Methods: Forty male Wistar albino rats were...

  19. Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

    Science.gov (United States)

    Alvarez, Pedro; Green, Paul G; Levine, Jon D

    2018-06-01

    Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  20. Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia.

    Science.gov (United States)

    Chiappelli, Joshua; Rowland, Laura M; Notarangelo, Francesca M; Wijtenburg, S Andrea; Thomas, Marian A R; Pocivavsek, Ana; Jones, Aaron; Wisner, Krista; Kochunov, Peter; Schwarcz, Robert; Hong, L Elliot

    2018-04-18

    Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia. In 56 patients with schizophrenia and 58 healthy controls, our results confirm that levels of KYNA in saliva increase following psychological stress. The magnitude of the effect correlated negatively with proton magnetic resonance spectroscopy (MRS) glutamate + glutamine (r = -.31, p = .017) and glutamate (r = -0.27, p = .047) levels in the ACC in patients but not in the controls (all p ≥ .45). Although, a causal relationship cannot be ascertained in this cross-sectional study, these findings suggest a potentially meaningful link between central glutamate levels and kynurenine pathway response to stress in individuals with schizophrenia.

  1. Stress-Induced Proton Disorder in Hydrous Ringwoodite

    Science.gov (United States)

    Koch-Müller, M.; Rhede, D.; Mrosko, M.; Speziale, S.; Schade, U.

    2008-12-01

    observed up to 30 GPa without any discontinuity and their pressure behaviour (dν/dP) can well be described by linear fits. Molecular vibrations are very sensitive to non-hydrostatic conditions and we interpret the disappearance of the OH-bands as a stress-induced proton disordering in hydrous ringwoodite due to the use of hard pressure transmiting media like CsI or argon without thermal annealing. Thus, our study cannot confirm the phase transition observed by Camorro Perez et al. (2006) in ringwoodite. But as they used Neon as pressure transmitting medium, which is known to become non-hydrostatic at pressure above 16 GPa (Bell and Mao, 1981) we argue that their observation of a sudden disappearance of the OH band may also be related to non-hydrostatic conditions. References Bell P.M. and Mao H.-K. (1981) Carnegie Inst. Wash Yrbk 80: 404-406. Camorro Perez E.M., Daniel I., Chervin J.-C., Dumas P., Bass J.D. and Inoue T. (2006) Phys. Chem. Minerals, 33, 502 - 510. Kudoh Y., Kuribayashi T., Mizohata H., Ohtani E., (2000) Phys. Chem. Mineral. 27, 474-479. Wittlinger J., Fischer R., Wener S., ScheiderJ., Schulz J. (1997) Acta Cryst B53, 745 - 749.

  2. Modeling of glutamate-induced dynamical patterns

    DEFF Research Database (Denmark)

    Faurby-Bentzen, Christian Krefeld; Zhabotinsky, A.M.; Laugesen, Jakob Lund

    2009-01-01

    Based on established physiological mechanisms, the paper presents a detailed computer model, which supports the hypothesis that temporal lobe epilepsy may be caused by failure of glutamate reuptake from the extracellular space. The elevated glutamate concentration causes an increased activation...

  3. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate...... or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...... of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must...

  4. Stress Induced Hyperglycemia and the Subsequent Risk of Type 2 Diabetes in Survivors of Critical Illness

    Science.gov (United States)

    Plummer, Mark P.; Finnis, Mark E.; Phillips, Liza K.; Kar, Palash; Bihari, Shailesh; Biradar, Vishwanath; Moodie, Stewart; Horowitz, Michael; Shaw, Jonathan E.; Deane, Adam M.

    2016-01-01

    Objective Stress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness. Design Retrospective cohort study. Setting All adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011. Patients Stress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression. Main Results Stress induced hyperglycemia was identified in 2,883 (17%) of 17,074 patients without diabetes. The incidence of type 2 diabetes following critical illness was 4.8% (821 of 17,074). The risk of diabetes in patients with stress induced hyperglycemia was approximately double that of those without (HR 1.91 (95% CI 1.62, 2.26), phyperglycemia identifies patients at subsequent risk of incident diabetes. PMID:27824898

  5. [Prediabetes as a riskmarker for stress-induced hyperglycemia in critically ill adults].

    Science.gov (United States)

    García-Gallegos, Diego Jesús; Luis-López, Eliseo

    2017-01-01

    It is not known if patients with prediabetes, a subgroup of non-diabetic patients that usually present hyperinsulinemia, have higher risk to present stress-induced hyperglycemia. The objective was to determine if prediabetes is a risk marker to present stress-induced hyperglycemia. Analytic, observational, prospective cohort study of non-diabetic critically ill patients of a third level hospital. We determined plasmatic glucose and glycated hemoglobin (HbA1c) at admission to diagnose stress-induced hyperglycemia (glucose ≥ 140 mg/dL) and prediabetes (HbA1c between 5.7 and 6.4%), respectively. We examined the proportion of non-prediabetic and prediabetic patients that developed stress hyperglycemia with contingence tables and Fisher's exact test for nominal scales. Of 73 patients studied, we found a proportion of stress-induced hyperglycemia in 6.6% in those without prediabetes and 61.1% in those with prediabetes. The Fisher's exact test value was 22.46 (p Prediabetes is a risk marker for stress-induced hyperglycemia in critically ill adults.

  6. 21 CFR 182.1045 - Glutamic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) [Reserved] (c) Limitations, restrictions, or...

  7. Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells.

    Science.gov (United States)

    Hirata, Yoko; Yamada, Chika; Ito, Yuki; Yamamoto, Shotaro; Nagase, Haruna; Oh-Hashi, Kentaro; Kiuchi, Kazutoshi; Suzuki, Hiromi; Sawada, Makoto; Furuta, Kyoji

    2018-03-15

    The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis. This compound also exerted a protective effect on tunicamycin-induced ER stress to a lesser extent but had no effect on campthothecin-, etoposide- or staurosporine-induced apoptosis. In addition, GIF-0726-r was also found to be effective after the occurrence of oxidative stress. GIF-0726-r was capable of inhibiting reactive oxygen species accumulation and Ca 2+ influx, a presumed executor in cell death, and was capable of activating the antioxidant response element, which is a cis-acting regulatory element in promoter regions of several genes encoding phase II detoxification enzymes and antioxidant proteins. These results suggest that GIF-0726-r is a low-molecular-weight compound that prevents neuronal cell death through attenuation of oxidative stress. Among the more than 200 derivatives of the GIF-0726-r synthesized, we identified the 11 most potent activators of the antioxidant response element and characterized their neuroprotective activity in HT22 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair.

    Science.gov (United States)

    Chatterjee, Nimrat; Lin, Yunfu; Yotnda, Patricia; Wilson, John H

    2016-07-31

    Multiple pathways modulate the dynamic mutability of trinucleotide repeats (TNRs), which are implicated in neurodegenerative disease and evolution. Recently, we reported that environmental stresses induce TNR mutagenesis via stress responses and rereplication, with more than 50% of mutants carrying deletions or insertions-molecular signatures of DNA double-strand break repair. We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and NHEJ, which have no effect. Thus, alt-NHEJ, which contributes to genetic mutability in cancer cells, also plays a novel role in environmental stress-induced TNR mutagenesis. Published by Elsevier Ltd.

  9. Stress-induced release of GUT peptides in young women classified as restrained or unrestrained eaters.

    Science.gov (United States)

    Hilterscheid, Esther; Laessle, Reinhold

    2015-12-01

    Basal release of GUT peptides has been found to be altered in restrained eaters. Stress-induced secretion, however, has not yet been described, but could be a biological basis of overeating that exposes restrained eaters to a higher risk of becoming obese. The aim of the present study was to compare restrained and unrestrained eaters with respect to stress-induced release of the GUT peptides ghrelin and PYY. 46 young women were studied. Blood sampling for peptides was done before and after the Trier Social Stress Test. Ghrelin secretion after stress was significantly elevated in the restrained eaters, whereas no significant differences were detected for PYY. Stress-induced release of GUT peptides can be interpreted as a cause as well as a consequence of restrained eating.

  10. Structure-dependent behavior of stress-induced voiding in Cu interconnects

    International Nuclear Information System (INIS)

    Wu Zhenyu; Yang Yintang; Chai Changchun; Li Yuejin; Wang Jiayou; Li Bin; Liu Jing

    2010-01-01

    Stress modeling and cross-section failure analysis by focused-ion-beam have been used to investigate stress-induced voiding phenomena in Cu interconnects. The voiding mechanism and the effect of the interconnect structure on the stress migration have been studied. The results show that the most concentrated tensile stress appears and voids form at corners of vias on top surfaces of Cu M1 lines. A simple model of stress induced voiding in which vacancies arise due to the increase of the chemical potential under tensile stress and diffuse under the force of stress gradient along the main diffusing path indicates that stress gradient rather than stress itself determines the voiding rate. Cu interconnects with larger vias show less resistance to stress-induced voiding due to larger stress gradient at corners of vias.

  11. Fluorescence imaging of glutamate release in neurons

    International Nuclear Information System (INIS)

    Wang, Ziqiang; Yeung, Edward S.

    1999-01-01

    A noninvasive detection scheme based on glutamate dehydrogenase (GDH) enzymatic assay combined with microscopy was developed to measure the glutamate release in cultured cells from the central nervous system (CNS). The enzyme reaction is very specific and sensitive. The detection limit with charge-coupled device (CCD) imaging is down to μM levels of glutamate with reasonable response time (∼30 s). The standard glutamate test shows a linear response over 3 orders of magnitude, from μM to 0.1 mM range. The in vitro monitoring of glutamate release from cultured neuron cells demonstrated excellent spatial and temporal resolution. (c) 1999 Society for Applied Spectroscopy

  12. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Sudhira Begum

    2007-12-01

    Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

  13. Model for Stress-induced Protein Degradation in Lemna minor1

    Science.gov (United States)

    Cooke, Robert J.; Roberts, Keith; Davies, David D.

    1980-01-01

    Transfer of Lemna minor fronds to adverse or stress conditions produces a large increase in the rate of protein degradation. Cycloheximide partially inhibits stress-induced protein degradation and also partially inhibits the protein degradation which occurs in the absence of stress. The increased protein degradation does not appear to be due to an increase in activity of soluble proteolytic enzymes. Biochemical evidence indicates that stress, perhaps acting via hormones, affects the permeability of certain membranes, particularly the tonoplast. A general model for stress-induced protein degradation is presented in which changes in membrane properties allow vacuolar proteolytic enzymes increased access to cytoplasmic proteins. PMID:16661588

  14. Group I Metabotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Erichsen, Julie Ladeby; Blaabjerg, Morten; Bogetofte Thomasen, Helle

    2015-01-01

    differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were...

  15. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

    Science.gov (United States)

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

  16. Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis

    Directory of Open Access Journals (Sweden)

    Maria Razzoli

    2016-01-01

    Conclusion: Our findings demonstrate that thermogenesis and BAT function are determinant of the resilience or vulnerability to stress-induced obesity. Our data support a model in which adrenergic and purinergic pathways exert complementary/synergistic functions in BAT, thus suggesting an alternative to βARs agonists for the activation of human BAT.

  17. Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

    Directory of Open Access Journals (Sweden)

    Lim Sung-Chul

    2011-09-01

    Full Text Available Abstract Background In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1, and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood. Results In the present study, we show that Distal-less 2 (Dlx-2, a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS in response to glucose deprivation (GD, one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH release, indicating the important role(s of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis. Conclusions These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.

  18. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli

    NARCIS (Netherlands)

    Oei, N.Y.L.; Both, S.; van Heemst, D.; van der Grond, J.

    2014-01-01

    Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in

  19. The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

    NARCIS (Netherlands)

    van Roosmalen, Ingrid A. M.; Dos Reis, Carlos R; Setroikromo, Rita; Yuvaraj, Saravanan; Joseph, Justin V.; Tepper, Pieter G.; Kruyt, Frank A. E.; Quax, Wim J.

    2014-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related

  20. Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

    DEFF Research Database (Denmark)

    Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning

    2006-01-01

    Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adre...

  1. Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts

    DEFF Research Database (Denmark)

    Le Boulch, Marine; Ahmed, Emad K; Rogowska-Wrzesinska, Adelina

    2018-01-01

    Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi-pro...

  2. Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

    International Nuclear Information System (INIS)

    Song Jun; Li Jing; Mourot, Joshua M.; Mark Evers, B.; Chung, Dai H.

    2008-01-01

    We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)ζ, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKζ siRNA transfection decreased H 2 O 2 -induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKζ also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKζ rapidly translocated to the cytoplasm following H 2 O 2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKζ, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells

  3. Stress-induced osteolysis of distal clavicle: imaging patterns and treatment using CT-guided injection

    Energy Technology Data Exchange (ETDEWEB)

    Sopov, V.; Groshar, D. [Dept. of Nuclear Medicine, Technion-Israel Inst. of Technology, Haifa (Israel); Fuchs, D. [Dept. of Orthopaedics, Technion-Israel Inst. of Technology, Haifa (Israel); Bar-Meir, E. [Dept. of Radiology, Technion-Israel Inst. of Technology, Haifa (Israel)

    2001-02-01

    Osteolysis of distal clavicle (ODC) may occur in patients who experience repeated stress or microtrauma to the shoulder. This entity has clinical and radiological findings similar to post-traumatic ODC. We describe a case of successful treatment of stress-induced ODC with CT-guided injection of corticosteroid and anesthetic drug into the acromioclavicular joint. (orig.)

  4. Stress-induced osteolysis of distal clavicle: imaging patterns and treatment using CT-guided injection

    International Nuclear Information System (INIS)

    Sopov, V.; Groshar, D.; Fuchs, D.; Bar-Meir, E.

    2001-01-01

    Osteolysis of distal clavicle (ODC) may occur in patients who experience repeated stress or microtrauma to the shoulder. This entity has clinical and radiological findings similar to post-traumatic ODC. We describe a case of successful treatment of stress-induced ODC with CT-guided injection of corticosteroid and anesthetic drug into the acromioclavicular joint. (orig.)

  5. Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

    OpenAIRE

    Kim, Ji-Seok; Kim, Boa; Lee, Hojun; Thakkar, Sunny; Babbitt, Dianne M.; Eguchi, Satoru; Brown, Michael D.; Park, Joon-Young

    2015-01-01

    This study assesses effects of aerobic exercise training on the release of microparticles from endothelial cells and corroborates these findings using an in vitro experimental exercise stimulant, laminar shear stress. Furthermore, this study demonstrated that shear stress-induced mitochondrial biogenesis mediates these effects against endothelial cell activation and injury.

  6. Ghrelin mediates stress-induced food-reward behavior in mice.

    Science.gov (United States)

    Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M; Lutter, Michael; Zigman, Jeffrey M

    2011-07-01

    The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

  7. Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

    Science.gov (United States)

    Wang, Yongfu; Wu, Jing; Zhu, Bi; Li, Chaocui; Cai, Jing-Xia

    2012-03-01

    It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

  8. C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.

    Science.gov (United States)

    Nath, Ravi D; Chow, Elly S; Wang, Han; Schwarz, Erich M; Sternberg, Paul W

    2016-09-26

    The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep-pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus-and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo

    NARCIS (Netherlands)

    Elassiuty, Yasser E.; Klarquist, Jared; Speiser, Jodi; Yousef, Randa M.; El Refaee, Abdelaziz A.; Hunter, Nahla S.; Shaker, Olfat G.; Gundeti, Mohan; Nieuweboer-Krobotova, Ludmila; Caroline Le Poole, I.

    2011-01-01

    To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP.

  10. Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

    2014-10-01

    This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

  11. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    Science.gov (United States)

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  12. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    . This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor...... released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion...

  13. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    DEFF Research Database (Denmark)

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... on glutamate metabolism in astrocytes was studied using primary cultures of these cells from mouse cerebral cortex during incubation in media containing 2.5 mM glucose and 100 µM [U-(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its metabolic pathways involving the tricarboxylic...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  14. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor....... This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate...

  15. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; van Wamelen, D.J.; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the

  16. Possible relationship between the stress-induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats.

    Science.gov (United States)

    Hirata, Riki; Matsumoto, Machiko; Judo, Chika; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro; Togashi, Hiroko

    2009-07-01

    Hippocampal long-term potentiation (LTP) is suppressed not only by stress paradigms but also by low frequency stimulation (LFS) prior to LTP-inducing high frequency stimulation (HFS; tetanus), termed metaplasticity. These synaptic responses are dependent on N-methyl-D-aspartate receptors, leading to speculations about the possible relationship between metaplasticity and stress-induced LTP impairment. However, the functional significance of metaplasticity has been unclear. The present study elucidated the electrophysiological and neurochemical profiles of metaplasticity in the hippocampal CA1 field, with a focus on the synaptic response induced by the emotional stress, contextual fear conditioning (CFC). The population spike amplitude in the CA1 field was decreased during exposure to CFC, and LTP induction was suppressed after CFC in conscious rats. The synaptic response induced by CFC was mimicked by LFS, i.e., LFS impaired the synaptic transmission and subsequent LTP. Plasma corticosterone levels were increased by both CFC and LFS. Extracellular levels of gamma-aminobutyric acid (GABA), but not glutamate, in the hippocampus increased during exposure to CFC or LFS. Furthermore, electrical stimulation of the medial prefrontal cortex (mPFC), which caused decreases in freezing behavior during exposure to CFC, counteracted the LTP impairment induced by LFS. These findings suggest that metaplasticity in the rat hippocampal CA1 field is related to the neural basis of stress experience-dependent fear memory, and that hippocampal synaptic response associated stress-related processes is under mPFC regulation.

  17. A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

    2010-05-01

    Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

  18. A study on anti-stress property of Nardostachys jatamamsi on stress induced Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Shilpashree R.

    2011-09-01

    Full Text Available Stress is a feeling that’s created when we react to particular events. It s the body’s way of rising to a challenge and preparing to meet a tough situation with focus, strength, stamina, and heightened alertness. As a result of the stress immune system can be suppressed by chronic stress opening to increased infections and increasing the risk of autoimmune diseases. So one has to learn away to overcome stress. Here is an attempt made to overcome the stress induced in Drosophila melanogaster a model organism, in this study. Methotrexate is used to induce the stress at different concentration taking different group of flies and a Nardostachys jatamamsi plant extract having antistress property is used to relieve the stress induced. This stress relieve measured by the various stress related enzymes like catalase and Superoxide dismutase by this antistress property of the plant Nardostachys jatamamsi was shown.

  19. Sociotropic cognition moderates stress-induced cardiovascular responsiveness in college women.

    Science.gov (United States)

    Sauro, M D; Jorgensen, R S; Larson, C A; Frankowski, J J; Ewart, C K; White, J

    2001-10-01

    This study examined the moderating effects of sociotropic cognition (SC), a nondefensive need for approval, on stress-induced cardiovascular responsiveness (CVR) in women. Sixty-seven college-age females had blood pressure (BP) and heart rate (HR) monitored during baseline, anticipation, story-telling (where participants were randomly assigned to a low or high threat condition), and recovery periods. SC showed a positive association with CVR only in the high interpersonal threat context during task and early stages of the recovery periods. SC was positively correlated with such variables as anxiety, ruminative style, dysphoria, and anger. This is the first report examining the moderating effects of SC on interpersonal stress-induced CVR prior to, during, and following a task, using an explicit manipulation of social evaluation. The data help define risk factors for CVR in women, which may aid in the understanding of how emotions and stress affect physical health and well-being.

  20. Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis

    Science.gov (United States)

    Sun, Xin-zhi; Liao, Ying; Li, Wei; Guo, Li-mei

    2017-01-01

    Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H2O2) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H2O2-induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects. PMID:28761429

  1. Photostress analysis of stress-induced martensite phase transformation in superelastic NiTi

    International Nuclear Information System (INIS)

    Katanchi, B.; Choupani, N.; Khalil-Allafi, J.; Baghani, M.

    2017-01-01

    Phase transformation in shape memory alloys is the most important factor in their unique behavior. In this paper, the formation of stress induced martensite phase transformation in a superelastic NiTi (50.8% Ni) shape memory alloy was investigated by using the photo-stress method. First, the material's fabrication procedure has been described and then the material was studied using the metallurgical tests such as differential scanning calorimetry and X-ray diffraction to characterize the material features and the mechanical tensile test to investigate the superelastic behavior. As a new method in observation of the phase transformation, photo-stress pictures showed the formation of stress induced martensite in a superelastic dog-bone specimen during loading and subsequently it's disappearing during unloading. Finally, finite element analysis was implemented using the constitutive equations derived based on the Boyd-Lagoudas phenomenological model.

  2. Experimental study of stress-induced localized transformation plastic zones in tetragonal zirconia polycrystalline ceramics

    International Nuclear Information System (INIS)

    Sun, Q.; Zhao, Z.; Chen, W.; Qing, X.; Xu, X.; Dai, F.

    1994-01-01

    Stress-induced martensitic transformation plastic zones in ceria-stabilized tetragonal zirconia polycrystalline ceramics (Ce-TZP), under loading conditions of uniaxial tension, compression, and three-point bending, are studied by experiments. The transformed monoclinic phase volume fraction distribution and the corresponding plastic strain distribution and the surface morphology (surface uplift) are measured by means of moire interferometry, Raman microprobe spectroscopy, and the surface measurement system. The experimental results from the above three kinds of specimens and methods consistently show that the stress-induced transformation at room temperature of the above specimen is not uniform within the transformation zone and that the plastic deformation is concentrated in some narrow band; i.e., macroscopic plastic flow localization proceeds during the initial stage of plastic deformation. Flow localization phenomena are all observed in uniaxial tension, compression, and three-point bending specimens. Some implications of the flow localization to the constitutive modeling and toughening of transforming thermoelastic polycrystalline ceramics are explored

  3. Photostress analysis of stress-induced martensite phase transformation in superelastic NiTi

    Energy Technology Data Exchange (ETDEWEB)

    Katanchi, B. [Mechanical Engineering Faculty, Sahand University of Technology, Tabriz (Iran, Islamic Republic of); Choupani, N., E-mail: choupani@sut.ac.ir [Mechanical Engineering Faculty, Sahand University of Technology, Tabriz (Iran, Islamic Republic of); Khalil-Allafi, J. [Research Center for Advance Materials, Faculty of Materials Engineering, Sahand University of Technology, Tabriz (Iran, Islamic Republic of); Baghani, M. [School of Mechanical Engineering, College of Engineering, University of Tehran (Iran, Islamic Republic of)

    2017-03-14

    Phase transformation in shape memory alloys is the most important factor in their unique behavior. In this paper, the formation of stress induced martensite phase transformation in a superelastic NiTi (50.8% Ni) shape memory alloy was investigated by using the photo-stress method. First, the material's fabrication procedure has been described and then the material was studied using the metallurgical tests such as differential scanning calorimetry and X-ray diffraction to characterize the material features and the mechanical tensile test to investigate the superelastic behavior. As a new method in observation of the phase transformation, photo-stress pictures showed the formation of stress induced martensite in a superelastic dog-bone specimen during loading and subsequently it's disappearing during unloading. Finally, finite element analysis was implemented using the constitutive equations derived based on the Boyd-Lagoudas phenomenological model.

  4. Glutamate: Tastant and Neuromodulator in Taste Buds.

    Science.gov (United States)

    Vandenbeuch, Aurelie; Kinnamon, Sue C

    2016-07-01

    In taste buds, glutamate plays a double role as a gustatory stimulus and neuromodulator. The detection of glutamate as a tastant involves several G protein-coupled receptors, including the heterodimer taste receptor type 1, member 1 and 3 as well as metabotropic glutamate receptors (mGluR1 and mGluR4). Both receptor types participate in the detection of glutamate as shown with knockout animals and selective antagonists. At the basal part of taste buds, ionotropic glutamate receptors [N-methyl-d-aspartate (NMDA) and non-NMDA] are expressed and participate in the modulation of the taste signal before its transmission to the brain. Evidence suggests that glutamate has an efferent function on taste cells and modulates the release of other neurotransmitters such as serotonin and ATP. This short article reviews the recent developments in the field with regard to glutamate receptors involved in both functions as well as the influence of glutamate on the taste signal. © 2016 American Society for Nutrition.

  5. UHPLC-MS/MS based target profiling of stress-induced phytohormones

    Czech Academy of Sciences Publication Activity Database

    Floková, Kristýna; Tarkowská, Danuše; Miersch, Otto; Strnad, Miroslav; Wasternack, Claus; Novák, Ondřej

    2014-01-01

    Roč. 105, SEP 2014 (2014), s. 147-157 ISSN 0031-9422 R&D Projects: GA ČR GA14-34792S; GA MŠk(CZ) LO1204; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : Stress-induced phytohormones * Jasmonates * Abscisic acid Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.547, year: 2014

  6. Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

    Directory of Open Access Journals (Sweden)

    Francesco Matrisciano

    Full Text Available The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1, an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central

  7. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli

    OpenAIRE

    Oei, Nicole Y. L.; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

    2014-01-01

    Summary Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain’s ‘‘reward system’’, and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PETstudies indicate that the stress hormone cortisol may be crucial in the interaction between st...

  8. Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Nishizawa, Osamu

    2015-01-01

    To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group). At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats. A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs. © 2014 Wiley Publishing Asia Pty Ltd.

  9. Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

    Science.gov (United States)

    Michopoulos, Vasiliki

    2016-11-01

    The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

  10. Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain.

    Science.gov (United States)

    Schwabe, Lars; Tegenthoff, Martin; Höffken, Oliver; Wolf, Oliver T

    2013-12-01

    Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR. Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum. Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance. Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR. © 2013 Society of Biological Psychiatry.

  11. Adolescent Personality: Associations With Basal, Awakening, and Stress-Induced Cortisol Responses

    OpenAIRE

    Laceulle, Odilia M.; Nederhof, Esther; van Aken, Marcel A. G.; Ormel, Johan

    2015-01-01

    The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n=343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective...

  12. The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma

    Directory of Open Access Journals (Sweden)

    Tomomitsu Miyasaka

    2018-01-01

    Full Text Available Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a “neuropsychiatry phenotype” in asthma.

  13. Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration.

    Science.gov (United States)

    Strekalova, Tatyana; Spanagel, Rainer; Bartsch, Dusan; Henn, Fritz A; Gass, Peter

    2004-11-01

    In order to develop a model for a depression-like syndrome in mice, we subjected male C57BL/6 mice to a 4-week-long chronic stress procedure, consisting of rat exposure, restraint stress, and tail suspension. This protocol resulted in a strong decrease in sucrose preference, a putative indicator of anhedonia in rodents. Interestingly, predisposition for stress-induced anhedonia was indicated by submissive behavior in a resident-intruder test. In contrast, most mice with nonsubmissive behavior did not develop a decrease in sucrose preference and were regarded as nonanhedonic. These animals were used as an internal control for stress-induced behavioral features not associated with the anhedonic state, since they were exposed to the same stressors as the anhedonic mice. Using a battery of behavioral tests after termination of the stress procedure, we found that anhedonia, but not chronic stress per se, is associated with key analogues of depressive symptoms, such as increased floating during forced swimming and decreased exploration of novelty. On the other hand, increased anxiety, altered locomotor activity, and loss of body weight were consequences of chronic stress, which occurred independently from anhedonia. Thus, behavioral correlates of stress-induced anhedonia and of chronic stress alone can be separated in the present model.

  14. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

    Science.gov (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

    2017-05-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

  15. Transcription regulator TRIP-Br2 mediates ER stress-induced brown adipocytes dysfunction.

    Science.gov (United States)

    Qiang, Guifen; Whang Kong, Hyerim; Gil, Victoria; Liew, Chong Wee

    2017-01-09

    In contrast to white adipose tissue, brown adipose tissue (BAT) is known to play critical roles for both basal and inducible energy expenditure. Obesity is associated with reduction of BAT function; however, it is not well understood how obesity promotes BAT dysfunction, especially at the molecular level. Here we show that the transcription regulator TRIP-Br2 mediates ER stress-induced inhibition of lipolysis and thermogenesis in BAT. Using in vitro, ex vivo, and in vivo approaches, we demonstrate that obesity-induced inflammation upregulates brown adipocytes TRIP-Br2 expression via the ER stress pathway and amelioration of ER stress in mice completely abolishes high fat diet-induced upregulation of TRIP-Br2 in BAT. We find that increased TRIP-Br2 significantly inhibits brown adipocytes thermogenesis. Finally, we show that ablation of TRIP-Br2 ameliorates ER stress-induced inhibition on lipolysis, fatty acid oxidation, oxidative metabolism, and thermogenesis in brown adipocytes. Taken together, our current study demonstrates a role for TRIP-Br2 in ER stress-induced BAT dysfunction, and inhibiting TRIP-Br2 could be a potential approach for counteracting obesity-induced BAT dysfunction.

  16. Geranylgeranylacetone prevents stress-induced decline of leptin secretion in mice.

    Science.gov (United States)

    Itai, Miki; Kuwano, Yuki; Nishikawa, Tatsuya; Rokutan, Kazuhito; Kensei, Nishida

    2018-01-01

    Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

  17. Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

    Science.gov (United States)

    Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

    2013-01-01

    In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

  18. First interactions between hydrogen and stress-induced reverse transformation of Ni-Ti superelastic alloy

    Science.gov (United States)

    Yokoyama, Ken'ichi; Hashimoto, Tatsuki; Sakai, Jun'ichi

    2017-11-01

    The first dynamic interactions between hydrogen and the stress-induced reverse transformation have been investigated by performing an unloading test on a Ni-Ti superelastic alloy subjected to hydrogen charging under a constant applied strain in the elastic deformation region of the martensite phase. Upon unloading the specimen, charged with a small amount of hydrogen, no change in the behaviour of the stress-induced reverse transformation is observed in the stress-strain curve, although the behaviour of the stress-induced martensite transformation changes. With increasing amount of hydrogen charging, the critical stress for the reverse transformation markedly decreases. Eventually, for a larger amount of hydrogen charging, the reverse transformation does not occur, i.e. there is no recovery of the superelastic strain. The residual martensite phase on the side surface of the unloaded specimen is confirmed by X-ray diffraction. Upon training before the unloading test, the properties of the reverse transformation slightly recover after ageing in air at room temperature. The present study indicates that to change the behaviour of the reverse transformation a larger amount of hydrogen than that for the martensite transformation is necessary. In addition, it is likely that a substantial amount of hydrogen in solid solution more strongly suppresses the reverse transformation than hydrogen trapped at defects, thereby stabilising the martensite phase.

  19. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6

    Directory of Open Access Journals (Sweden)

    Rong Liu

    2014-01-01

    Full Text Available Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated retinoblastoma (Rb protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.

  20. Stress Induced Cardiomyopathy Triggered by Acute Myocardial Infarction: A Case Series Challenging the Mayo Clinic Definition.

    Science.gov (United States)

    Christodoulidis, Georgios; Kundoor, Vishwa; Kaluski, Edo

    2017-08-28

    BACKGROUND Various physical and emotional factors have been previously described as triggers for stress induced cardiomyopathy. However, acute myocardial infarction as a trigger has never been reported. CASE REPORT We describe four patients who presented with an acute myocardial infarction, in whom the initial echocardiography revealed wall motion abnormalities extending beyond the coronary distribution of the infarct artery. Of the four patients identified, the mean age was 59 years; three patients were women and two patients had underlying psychiatric history. Electrocardiogram revealed ST elevation in the anterior leads in three patients; QTc was prolonged in all cases. All patients had ≤ moderately elevated troponin. Single culprit lesion was found uniformly in the proximal or mid left anterior descending artery. Initial echocardiography revealed severely reduced ejection fraction with relative sparing of the basal segments, whereas early repeat echocardiography revealed significant improvement in the left ventricular function in all patients. CONCLUSIONS This is the first case series demonstrating that acute myocardial infarction can trigger stress induced cardiomyopathy. Extensive reversible wall motion abnormalities, beyond the ones expected from angiography, accompanied by modest elevation in troponin and marked QTc prolongation, suggest superimposed stress induced cardiomyopathy.

  1. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

    Science.gov (United States)

    Viswanathan, Kavitha; Dhabhar, Firdaus S.

    2005-04-01

    Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

  2. Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

    International Nuclear Information System (INIS)

    Chen, Y.; Puplampu, S.B.; Summers, P.T.; Lattimer, B.Y.; Penumadu, D.; Case, S.W.

    2015-01-01

    One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep

  3. Secondary aerosol formation from stress-induced biogenic emissions and possible climate feedbacks

    Directory of Open Access Journals (Sweden)

    Th. F. Mentel

    2013-09-01

    Full Text Available Atmospheric aerosols impact climate by scattering and absorbing solar radiation and by acting as ice and cloud condensation nuclei. Biogenic secondary organic aerosols (BSOAs comprise an important component of atmospheric aerosols. Biogenic volatile organic compounds (BVOCs emitted by vegetation are the source of BSOAs. Pathogens and insect attacks, heat waves and droughts can induce stress to plants that may impact their BVOC emissions, and hence the yield and type of formed BSOAs, and possibly their climatic effects. This raises questions of whether stress-induced changes in BSOA formation may attenuate or amplify effects of climate change. In this study we assess the potential impact of stress-induced BVOC emissions on BSOA formation for tree species typical for mixed deciduous and Boreal Eurasian forests. We studied the photochemical BSOA formation for plants infested by aphids in a laboratory setup under well-controlled conditions and applied in addition heat and drought stress. The results indicate that stress conditions substantially modify BSOA formation and yield. Stress-induced emissions of sesquiterpenes, methyl salicylate, and C17-BVOCs increase BSOA yields. Mixtures including these compounds exhibit BSOA yields between 17 and 33%, significantly higher than mixtures containing mainly monoterpenes (4–6% yield. Green leaf volatiles suppress SOA formation, presumably by scavenging OH, similar to isoprene. By classifying emission types, stressors and BSOA formation potential, we discuss possible climatic feedbacks regarding aerosol effects. We conclude that stress situations for plants due to climate change should be considered in climate–vegetation feedback mechanisms.

  4. Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yanyun@vt.edu [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States); Puplampu, S.B. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Summers, P.T.; Lattimer, B.Y. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061 (United States); Penumadu, D. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Case, S.W. [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States)

    2015-08-12

    One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep.

  5. Laforin prevents stress-induced polyglucosan body formation and Lafora disease progression in neurons.

    Science.gov (United States)

    Wang, Yin; Ma, Keli; Wang, Peixiang; Baba, Otto; Zhang, Helen; Parent, Jack M; Zheng, Pan; Liu, Yang; Minassian, Berge A; Liu, Yan

    2013-08-01

    Glycogen, the largest cytosolic macromolecule, is soluble because of intricate construction generating perfect hydrophilic-surfaced spheres. Little is known about neuronal glycogen function and metabolism, though progress is accruing through the neurodegenerative epilepsy Lafora disease (LD) proteins laforin and malin. Neurons in LD exhibit Lafora bodies (LBs), large accumulations of malconstructed insoluble glycogen (polyglucosans). We demonstrated that the laforin-malin complex reduces LBs and protects neuronal cells against endoplasmic reticulum stress-induced apoptosis. We now show that stress induces polyglucosan formation in normal neurons in culture and in the brain. This is mediated by increased glucose-6-phosphate allosterically hyperactivating muscle glycogen synthase (GS1) and is followed by activation of the glycogen digesting enzyme glycogen phosphorylase. In the absence of laforin, stress-induced polyglucosans are undigested and accumulate into massive LBs, and in laforin-deficient mice, stress drastically accelerates LB accumulation and LD. The mechanism through which laforin-malin mediates polyglucosan degradation remains unclear but involves GS1 dephosphorylation by laforin. Our work uncovers the presence of rapid polyglucosan metabolism as part of the normal physiology of neuroprotection. We propose that deficiency in the degradative phase of this metabolism, leading to LB accumulation and resultant seizure predisposition and neurodegeneration, underlies LD.

  6. Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits.

    Science.gov (United States)

    Bogdanov, Mario; Schwabe, Lars

    2016-01-27

    Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal

  7. Glutamate and Brain Glutaminases in Drug Addiction.

    Science.gov (United States)

    Márquez, Javier; Campos-Sandoval, José A; Peñalver, Ana; Matés, José M; Segura, Juan A; Blanco, Eduardo; Alonso, Francisco J; de Fonseca, Fernando Rodríguez

    2017-03-01

    Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.

  8. A radiometric microassay for glutamic acid decarboxylase

    International Nuclear Information System (INIS)

    Maderdrut, J.L.; North Carolina Univ., Chapel Hill

    1979-01-01

    A simple method for purifying L-[ 3 H] glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating γ-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 μg. The cation-exchange method is compared with the anion-exchange and CO 2 -trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis. (author)

  9. Radiometric microassay for glutamic acid decarboxylase

    Energy Technology Data Exchange (ETDEWEB)

    Maderdrut, J L [North Carolina Dept. of Mental Health, Raleigh (USA); North Carolina Univ., Chapel Hill (USA). School of Medicine)

    1979-01-01

    A simple method for purifying L-(/sup 3/H) glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating ..gamma..-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 ..mu..g. The cation-exchange method is compared with the anion-exchange and CO/sub 2/-trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis.

  10. Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease.

    Science.gov (United States)

    Jiang, Wei; Samad, Zainab; Boyle, Stephen; Becker, Richard C; Williams, Redford; Kuhn, Cynthia; Ortel, Thomas L; Rogers, Joseph; Kuchibhatla, Maragatha; O'Connor, Christopher; Velazquez, Eric J

    2013-02-19

    The goal of this study was to evaluate the prevalence and clinical characteristics of mental stress-induced myocardial ischemia. Mental stress-induced myocardial ischemia is prevalent and a risk factor for poor prognosis in patients with coronary heart disease, but past studies mainly studied patients with exercise-induced myocardial ischemia. Eligible patients with clinically stable coronary heart disease, regardless of exercise stress testing status, underwent a battery of 3 mental stress tests followed by a treadmill test. Stress-induced ischemia, assessed by echocardiography and electrocardiography, was defined as: 1) development or worsening of regional wall motion abnormality; 2) left ventricular ejection fraction reduction ≥ 8%; and/or 3) horizontal or downsloping ST-segment depression ≥ 1 mm in 2 or more leads lasting for ≥ 3 consecutive beats during at least 1 mental test or during the exercise test. Mental stress-induced ischemia occurred in 43.45%, whereas exercise-induced ischemia occurred in 33.79% (p = 0.002) of the study population (N = 310). Women (odds ratio [OR]: 1.88), patients who were not married (OR: 1.99), and patients who lived alone (OR: 2.24) were more likely to have mental stress-induced ischemia (all p mental stress-induced ischemia (all p Mental stress-induced ischemia is more common than exercise-induced ischemia in patients with clinically stable coronary heart disease. Women, unmarried men, and individuals living alone are at higher risk for mental stress-induced ischemia. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig.

    Science.gov (United States)

    Wei, Lihua; Ge, Li; Qin, Shucun; Shi, Yunzhi; Du, Changqing; Du, Hui; Liu, Liwei; Yu, Yang; Sun, Xuejun

    2012-01-01

    Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Overlapping mechanisms of stress-induced relapse to opioid use disorder and chronic pain: Clinical implications

    Directory of Open Access Journals (Sweden)

    Udi E Ghitza

    2016-05-01

    Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.

  13. Stress-Induced Cubic-to-Hexagonal Phase Transformation in Perovskite Nanothin Films.

    Science.gov (United States)

    Cao, Shi-Gu; Li, Yunsong; Wu, Hong-Hui; Wang, Jie; Huang, Baoling; Zhang, Tong-Yi

    2017-08-09

    The strong coupling between crystal structure and mechanical deformation can stabilize low-symmetry phases from high-symmetry phases or induce novel phase transformation in oxide thin films. Stress-induced structural phase transformation in oxide thin films has drawn more and more attention due to its significant influence on the functionalities of the materials. Here, we discovered experimentally a novel stress-induced cubic-to-hexagonal phase transformation in the perovskite nanothin films of barium titanate (BaTiO 3 ) with a special thermomechanical treatment (TMT), where BaTiO 3 nanothin films under various stresses are annealed at temperature of 575 °C. Both high-resolution transmission electron microscopy and Raman spectroscopy show a higher density of hexagonal phase in the perovskite thin film under higher tensile stress. Both X-ray photoelectron spectroscopy and electron energy loss spectroscopy does not detect any change in the valence state of Ti atoms, thereby excluding the mechanism of oxygen vacancy induced cubic-to-hexagonal (c-to-h) phase transformation. First-principles calculations show that the c-to-h phase transformation can be completed by lattice shear at elevated temperature, which is consistent with the experimental observation. The applied bending plus the residual tensile stress produces shear stress in the nanothin film. The thermal energy at the elevated temperature assists the shear stress to overcome the energy barriers during the c-to-h phase transformation. The stress-induced phase transformation in perovskite nanothin films with TMT provides materials scientists and engineers a novel approach to tailor nano/microstructures and properties of ferroelectric materials.

  14. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Ayşin Akıncı

    2017-02-01

    Full Text Available Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57 was higher than that of the control group (1.50±0.22 (p<0.05. Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05, the stress and stress + standard diet groups (p<0.05, and the stress and stress + LPZ groups (p<0.05. The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05. Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50 and superoxide dismutase (15.18±1.05 and catalase (16.68±2.29 activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system

  15. Effect of vitamin D on stress-induced hyperglycaemia and insulin resistance in critically ill patients.

    Science.gov (United States)

    Alizadeh, N; Khalili, H; Mohammadi, M; Abdollahi, A; Ala, S

    2016-05-01

    Effects of vitamin D supplementation on the glycaemic indices and insulin resistance in diabetic and non-diabetic patients were studied. In this study, effects of vitamin D supplementation on stress-induced hyperglycaemia and insulin resistance were evaluated in non-diabetic surgical critically ill patients. Adult surgical patients with stress-induced hyperglycaemia within the first 24 h of admission to the ICU were recruited. The patients randomly assigned to receive either vitamin D or placebo. Patients in the vitamin D group received a single dose of 600,000 IU vitamin D3 as intramuscular injection at time of recruitment. Besides demographic and clinical characteristics of the patients, plasma glucose, insulin, 25(OH) D and adiponectin levels were measured at the time of ICU admission and day 7. Homoeostasis model assessment for insulin resistance (HOMA-IR) and homestasis model assessment adiponectin (HOMA-AD) ratio were considered at the times of assessment. Comparing with the baseline, plasma 25(OH) D level significantly increased in the subjects who received vitamin D (p = 0.04). Improvement in fasting plasma glucose levels was detected in day 7 of the study compared with the baseline status in both groups. HOMA-IR showed a decrement pattern in vitamin D group (p = 0.09). Fasting plasma adiponectin levels increased significantly in the vitamin D group (p = 0.007), but not in the placebo group (p = 0.38). Finally, changes in HOMA-AD ratio were not significant in the both groups. Vitamin D supplementation showed positive effect on plasma adiponectin level, as a biomarker of insulin sensitivity in surgical critically ill patients with stress-induced hyperglycaemia. However, effects of vitamin D supplementation on HOMA-IR and HOMA-AD as indicators of insulin resistance were not significant. © 2016 John Wiley & Sons Ltd.

  16. Differential effects of stress-induced cortisol responses on recollection and familiarity-based recognition memory.

    Science.gov (United States)

    McCullough, Andrew M; Ritchey, Maureen; Ranganath, Charan; Yonelinas, Andrew

    2015-09-01

    Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia.

    Science.gov (United States)

    Terrill, Sarah J; Maske, Calyn B; Williams, Diana L

    2018-03-03

    Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS). In a within-subjects design, shortly before the onset of the dark phase, rats received dLS injections of saline or the GLP-1R antagonist Exendin (9-39) (Ex9) prior to 30 min restraint stress. Food intake was measured continuously for the next 20 h. The stress-induced hypophagia observed within the first 30 min of dark was not influenced by Ex9 pretreatment, but Ex9 tended to blunt the effect of stress as early as 1 and 2 h into the dark phase. By 4-6 h, there were significant stress X drug interactions, and Ex9 pretreatment blocked the stress-induced suppression of feeding. These effects were mediated entirely through changes in average meal size; stress suppressed meal size while dLS Ex9 attenuated this effect. Using a similar design, we examined the role of dLS GLP-1R in the neuroendocrine response to acute restraint stress. As expected, stress potently increased serum corticosterone, but blockade of dLS GLP-1Rs did not affect this response. Together, these data show that endogenous GLP-1 action in the dLS plays a role in some but not all of the physiologic responses to acute stress. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving.

    Science.gov (United States)

    Epstein, David H; Kennedy, Ashley P; Furnari, Melody; Heilig, Markus; Shaham, Yavin; Phillips, Karran A; Preston, Kenzie L

    2016-12-01

    In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. To test anticraving properties of the CRF 1 antagonist pexacerfont in humans. We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS). The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r effect  = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect  = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics. The findings may support further investigation of the anticraving properties of CRF 1 antagonists, especially for food.

  19. Brain prolactin is involved in stress-induced REM sleep rebound.

    Science.gov (United States)

    Machado, Ricardo Borges; Rocha, Murilo Ramos; Suchecki, Deborah

    2017-03-01

    REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. GAD65 haplodeficiency conveys resilience in animal models of stress-induced psychopathology

    Directory of Open Access Journals (Sweden)

    Iris eMüller

    2014-08-01

    Full Text Available GABAergic mechanisms are critically involved in the control of fear and anxiety, but their role in the development of stress-induced psychopathologies, including post-traumatic stress disorder (PTSD and mood disorders is not sufficiently understood. We studied these functions in two established mouse models of risk factors for stress-induced psychopathologies employing variable juvenile stress and/or social isolation. A battery of emotional tests in adulthood revealed the induction of contextually generalized fear, anxiety, hyperarousal and depression-like symptoms in these paradigms. These reflect the multitude and complexity of stress effects in human PTSD patients. With factor analysis we were able to identify parameters that reflect these different behavioral domains in stressed animals and thus provide a basis for an integrated scoring of affectedness more closely resembling the clinical situation than isolated parameters. To test the applicability of these models to genetic approaches we further tested the role of GABA using heterozygous mice with targeted mutation of the GABA synthesizing enzyme GAD65 (GAD65+/- mice, which show a delayed postnatal increase in tissue GABA content in limbic and cortical brain areas. Unexpectedly, GAD65(+/- mice did not show changes in exploratory activity regardless of the stressor type and were after the variable juvenile stress procedure protected from the development of contextual generalization in an auditory fear conditioning experiment. Our data demonstrate the complex nature of behavioral alterations in rodent models of stress-related psychopathologies and suggest that GAD65 haplodeficiency, likely through its effect on the postnatal maturation of GABAergic transmission, conveys resilience to some of these stress-induced effects.

  1. Biobased synthesis of acrylonitrile from glutamic acid

    NARCIS (Netherlands)

    Notre, le J.E.L.; Scott, E.L.; Franssen, M.C.R.; Sanders, J.P.M.

    2011-01-01

    Glutamic acid was transformed into acrylonitrile in a two step procedure involving an oxidative decarboxylation in water to 3-cyanopropanoic acid followed by a decarbonylation-elimination reaction using a palladium catalyst

  2. Stress-induced eating in women with binge-eating disorder and obesity.

    Science.gov (United States)

    Klatzkin, Rebecca R; Gaffney, Sierra; Cyrus, Kathryn; Bigus, Elizabeth; Brownley, Kimberly A

    2018-01-01

    The purpose of the current study was to investigate stress-induced eating in women with binge-eating disorder (BED) and obesity. Three groups of women [obese with BED (n=9); obese non-BED (n=11); and normal weight (NW) non-BED (n=12)], rated their levels of hunger and psychological distress before and after completing the Trier Social Stress Test, followed by food anticipation and then consumption of their preferred snack food. We differentiated between the motivational and hedonic components of eating by measuring the amount of food participants poured into a serving bowl compared to the amount consumed. Stress did not affect poured and consumed calories differently between groups. Across all subjects, calories poured and consumed were positively correlated with post-stress hunger, but calories poured was positively correlated with post-stress anxiety and negative affect. These results indicate that stress-related psychological factors may be more strongly associated with the motivational drive to eat (i.e. amount poured) rather than the hedonic aspects of eating (i.e. amount consumed) for women in general. Exploratory correlation analyses per subgroup suggest that post-stress hunger was positively associated with calories poured and consumed in both non-BED groups. In the obese BED group, calories consumed was negatively associated with dietary restraint and, although not significantly, positively associated with stress-induced changes in anxiety.These findings suggest that stress-induced snacking in obese BED women may be influenced by psychological factors more so than homeostatic hunger mechanisms. After controlling for dietary restraint and negative affect, the NW non-BED women ate a greater percentage of the food they poured than both obese groups, suggesting that obesity may be associated with a heightened motivational drive to eat coupled with a reduction in hedonic pleasure from eating post-stress. Further studies that incorporate novel approaches to

  3. Basolateral amygdala GABA-A receptors mediate stress-induced memory retrieval impairment in rats.

    Science.gov (United States)

    Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba; Zarrindast, Mohammad-Reza

    2014-04-01

    The present study was designed to investigate the involvement of GABA-A receptors of the basolateral amygdala (BLA) in the impairing effect of acute stress on memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated and memory retrieval was measured in a step-through type passive avoidance apparatus. Acute stress was evoked by placing the animals on an elevated platform for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min stress, but not 10 min, before memory retrieval testing (pre-test exposure to stress) decreased the step-through latency, indicating stress-induced memory retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist, muscimol (0.005-0.02 μg/rat), 5 min before exposure to an ineffective stress (10 min exposure to stress) induced memory retrieval impairment. It is important to note that pre-test intra-BLA microinjection of the same doses of muscimol had no effect on memory retrieval in the rats unexposed to 10 min stress. The blockade of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5 μg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline (0.4-0.5 μg/rat) in rats unexposed to 20 min stress had no effect on memory retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 μg/rat, intra-BLA) reversed muscimol (0.02 μg/rat, intra-BLA)-induced potentiation on the effect of stress in passive avoidance learning. It can be concluded that pre-test exposure to stress can induce memory retrieval impairment and the BLA GABA-A receptors may be involved in stress-induced memory retrieval impairment.

  4. Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Motoharu Hayashi

    Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

  5. Stress Induced Charge-Ordering Process in LiMn_2O_4

    International Nuclear Information System (INIS)

    Chen, Yan; Yu, Dunji; An, Ke

    2016-01-01

    In this letter we report the stress-induced Mn charge-ordering process in the LiMn_2O_4 spinel, evidenced by the lattice strain evolutions due to the Jahn–Teller effects. In situ neutron diffraction reveals the initial stage of this process at low stress, indicating the eg electron localization at the preferential Mn sites during the early phase transition as an underlying charge-ordering mechanism in the charge-frustrated LiMn_2O_4. The initial stage of this transition exhibits as a progressive lattice and charge evolution, without showing a first-order behavior.

  6. Stress-induced state transitions in flexible liquid-crystal devices

    International Nuclear Information System (INIS)

    Ho, I-Lin; Chang, Yia-Chung

    2012-01-01

    This work studies the stress-strain dynamics for the transient optoelectronic characteristics of flexible liquid-crystal (LC) devices. Due to the fast response of LC directors, the configuration of the LC is assumed to be in quasi-equilibrium during the process of elastic deformations of the flexible structures. The LC medium hence can be treated effectively as a thin-film layer and can approximately follow the strain-stress mechanism in the solids. Relevant theoretical algorithms are studied in this work, and numerical results present the stress-induced state transitions in the π cell.

  7. Functional Comparison of the Two Bacillus anthracis Glutamate Racemases▿

    OpenAIRE

    Dodd, Dylan; Reese, Joseph G.; Louer, Craig R.; Ballard, Jimmy D.; Spies, M. Ashley; Blanke, Steven R.

    2007-01-01

    Glutamate racemase activity in Bacillus anthracis is of significant interest with respect to chemotherapeutic drug design, because l-glutamate stereoisomerization to d-glutamate is predicted to be closely associated with peptidoglycan and capsule biosynthesis, which are important for growth and virulence, respectively. In contrast to most bacteria, which harbor a single glutamate racemase gene, the genomic sequence of B. anthracis predicts two genes encoding glutamate racemases, racE1 and rac...

  8. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    Science.gov (United States)

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  9. Role of serotonin in the intestinal mucosal epithelium barrier in weaning mice undergoing stress-induced diarrhea.

    Science.gov (United States)

    Dong, Yulan; Wang, Zixu; Qin, Zhuoming; Cao, Jing; Chen, Yaoxing

    2018-02-01

    Stress-induced diarrhea is a frequent and challenging threat to humans and domestic animals. Serotonin (5-HT) has been shown to be involved in the pathological process of stress-induced diarrhea. However, the role of 5-HT in stress-induced diarrhea remains unclear. A stress-induced diarrhea model was established in 21-day-old ICR weaning mice through an intragastric administration of 0.25 mL of 0.4 g/mL folium sennae and restraint of the hind legs with adhesive tape for 4 h to determine whether 5-HT regulates the mucosal barrier to cause diarrhea. Mice with decreased levels of 5-HT were pretreated with an intraperitoneal injection of 300 mg/kg p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. After 5 days of treatment, the stress level, body weight and intestinal mucosal morphology indexes were measured. Compared to the controls, the mice with stress-induced diarrhea displayed a stress reaction, with increased corticosterone levels, as well as increased 5-HT-positive cells. However, the mice with stress-induced diarrhea exhibited decreased body weights, villus height to crypt depth ratios (V/C), and Occludin and Claudin1 expression. The PCPA injection reversed these effects in mice with different degrees of stress-induced diarrhea. Based on these findings, inhibition of 5-HT synthesis relieved the stress response and improved the health of the intestinal tract, including both the intestinal absorption capacity, as determined by the villus height and crypt depth, and the mucosal barrier function, as determined by the tight junction proteins of epithelial cell.

  10. Stress-induced deficits in working memory and visuo-constructive abilities in Special Operations soldiers.

    Science.gov (United States)

    Morgan, Charles A; Doran, Anthony; Steffian, George; Hazlett, Gary; Southwick, Steven M

    2006-10-01

    Pre-clinical and clinical studies have shown acute stress may impair working memory and visuo-spatial ability. This study was designed to clarify the nature of stress-induced cognitive deficits in soldiers and how such deficits may contribute to operational or battlefield errors. One hundred eighty-four Special Operations warfighters enrolled in Survival School completed pre-stress measures of dissociation and trauma exposure. Subjects were randomized to one of three assessment groups (Pre-stress, Stress, Post-stress) and were administered the Rey Ostereith Complex Figure (ROCF). All subjects completed post-stress measures of dissociation. ROCF copy and recall were normal in the Pre- and Post-stress groups. ROCF copy and recall were significantly impaired in the Stress Group. Stress group ROCF copy performance was piecemeal, and ROCF recall was impaired. Symptoms of dissociation were negatively associated with ROCF recall in the Stress group. Baseline dissociation and history of traumatic stress predicted cognitive impairment during stress. Stress exposure impaired visuo-spatial capacity and working memory. In rats, monkeys, and humans, high dopamine and NE turnover in the PFC induce deficits in cognition and spatial working memory. Improved understanding of stress-induced cognitive deficits may assist in identification of soldiers at risk and lead to the development of better countermeasures.

  11. Stress-induced accumulation of wheat germ agglutinin and abscisic acid in roots of wheat seedlings

    International Nuclear Information System (INIS)

    Cammue, B.P.A.; Broekaert, W.F.; Kellens, J.T.C.; Peumans, W.J.; Raikhel, N.V.

    1989-01-01

    Wheat germ agglutinin (WGA) levels in roots of 2-day-old wheat seedlings increased up to three-fold when stressed by air-drying. Similar results were obtained when seedling roots were incubated either in 0.5 molar mannitol or 180 grams per liter polyethylene glycol 6,000, with a peak level of WGA after 5 hours of stress. Longer periods of osmotic treatment resulted in a gradual decline of WGA in the roots. Since excised wheat roots incorporate more [ 35 S]cysteine into WGA under stress conditions, the observed increase of lectin levels is due to de novo synthesis. Measurement of abscisic acid (ABA) levels in roots of control and stressed seedlings indicated a 10-fold increase upon air-drying. Similarly, a five- and seven-fold increase of ABA content of seedling roots was found after 2 hours of osmotic stress by polyethylene glycol 6,000 and mannitol, respectively. Finally, the stress-induced increase of WGA in wheat roots could be inhibited by growing seedlings in the presence of fluridone, an inhibitor of ABA synthesis. These results indicate that roots of water-stressed wheat seedlings (a) contain more WGA as a result of an increased de novo synthesis of this lectin, and (b) exhibit higher ABA levels. The stress-induced increase of lectin accumulation seems to be under control of ABA

  12. Thermal Stress-Induced Depolarization Loss in Conventional and Panda-Shaped Photonic Crystal Fiber Lasers

    Science.gov (United States)

    Mousavi, Seyedeh Laleh; Sabaeian, Mohammad

    2016-10-01

    We report on the modeling of the depolarization loss in the conventional and panda-shaped photonic crystal fiber lasers (PCFLs) due to the self-heating of the fiber, which we call it thermal stress-induced depolarization loss (TSIDL). We first calculated the temperature distribution over the fiber cross sections and then calculated the thermal stresses/strains as a function of heat load per meter. Thermal stress-induced birefringence (TSIB), which is defined as | n x - n y |, in the core and cladding regions was calculated. Finally, TSIDL was calculated for the conventional and panda-shaped PCFLs as a function of fiber length and, respectively, saturated values of 22 and 25 % were obtained which were independent of heat load per meter. For panda-shaped PCFLs, prior to being saturated, an oscillating and damping behavior against the fiber length was seen where in some lengths reached 35 %. The results are close to an experimental value of 30 % reported for a pulsed PCFL (Limpert et al., Opt Express 12:1313-1319, 2004) where the authors reported a degree of polarization of 70 % (i.e., a depolarization of 30 %). The most important result of this work is a saturation behavior of TSIDL at long-enough lengths of the fiber laser which is independent of heat load per meter. To our knowledge, this the first report of TSIBL for PCFLs.

  13. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala.

    Science.gov (United States)

    Aubry, Antonio V; Serrano, Peter A; Burghardt, Nesha S

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR) and norepinephrine release within the amygdala leads to the mobilization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  14. Reward dependence moderates smoking-cue- and stress-induced cigarette cravings.

    Science.gov (United States)

    Michalowski, Alexandra; Erblich, Joel

    2014-12-01

    Cigarette cravings following exposure to smoking cues in a smoker's environment are thought to play an important role in cessation failure. The possibility that dispositional factors may impact cue-induced cravings, though intriguing, has received little attention. According to Cloninger's Tridimensional Personality Theory, factors such as reward dependence (RD), harm avoidance (HA), and novelty seeking (NS) may figure prominently in risk for addiction, as well as relapse, in individuals attempting to abstain from drug and alcohol use. Particularly interesting in this regard is the possibility that smokers with higher levels of RD, who are especially sensitive to reward signals, will have heightened craving reactions to smoking cues. To that end, non-treatment-seeking nicotine dependent smokers (n=96, mean age=41.1, 47% African American, 17% Caucasian, 22% Hispanic, 19.3cigs/day, FTND=7.5) underwent a classic experimental cue-induction, during which they were exposed to imagery of: (1) smoking, (2) neutral, and (3) stress cues, and reported their cigarette cravings (0-100) before and after each exposure. Participants also completed the Tridimensional Personality Questionnaire. Not surprisingly, smoking and stress cues (but not neutral cues) elicited significant elevations in craving (p'scues (pcues (pcues. Furthermore, the similar effects of RD on stress-induced craving suggest that both cue-and stress-induced cravings may be influenced by a common underlying disposition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Stress induced right ventricular dysfunction: An indication of reversible right ventricular ischaemia

    International Nuclear Information System (INIS)

    Underwood, S.R.; Walton, S.; Emanuel, R.W.; Swanton, R.H.; Campos Costa, D.; Laming, P.J.; Ell, P.J.

    1987-01-01

    Stress induced changes in left ventricular ejection fraction are widely used in the detection and assessment of coronary artery disease. This study demonstrates that right ventricular dysfunction may also occur, and assesses its significance in terms of coronary artery anatomy. This study involved 14 normal subjects and 26 with coronary artery disease investigated by equilibrium radionuclide ventriculography, at rest and during maximal dynamic exercise. Mean normal resting right ventricular ejection fraction (RVEF) was 0.40 (SD 0.118), and all normal subjects increased RVEF with stress (mean ΔRVEF+0.13 SD 0.099). Mean ΔRVEF in the subjects with coronary artery disease was significantly lower at 0.00 (SD 0.080), but there was overlap between the two groups. The largest falls in RVEF were seen if the right coronary artery was occluded without retrograde filling. In this subgroup with the most severely compromised right ventricular perfusion (nine subjects), RVEF always fell with stress, and mean ΔRVEF was -0.08 (SD 0.050). There was no significant correlation between ΔLVEF and ΔRVEF, implying that the right ventricular dysfunction was due to right ventricular ischaemia, rather than secondary to left ventricular dysfunction. Stress induced right ventricular ischaemia can therefore be detected readily by radionuclide ventriculography. (orig.)

  16. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    International Nuclear Information System (INIS)

    Shin, Jung Ar; Chung, Jin Sil; Cho, Sang-Ho; Kim, Hyung Jung; Yoo, Young Do

    2013-01-01

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H 2 O 2 ) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H 2 O 2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells

  17. Stress-induced martensitic transformation and ferroelastic deformation adjacent microhardness indents in tetragonal zirconia single crystals

    International Nuclear Information System (INIS)

    Chien, F.R.; Ubic, F.J.; Prakash, V.; Heuer, A.H.

    1998-01-01

    The stress-induced tetragonal to monoclinic (t → m) martensitic transformation, stress-induced ferroelastic domain switching, and dislocation slip were induced by Vickers microindentation at elevated temperatures in polydomain single crystals of 3 mol%-Y 2 O 3 -stabilized tetragonal ZrO 2 single crystals (3Y-TZS). Chemical etching revealed traces along t directions adjacent to indentations, and Raman spectroscopy and TEM have shown that these traces are caused by products of the martensitic transformation, i.e. the monoclinic product phase forms primarily as thin, long plates with a habit plane approximately on (bar 301) m . This habit plane and the associated shear strain arising from the transformation, visible in TEM micrographs at the intersection of crystallographically equivalent martensite plates, were successfully predicted using the observed lattice correspondence and the phenomenological invariant plane strain theory of martensitic transformations. The extent of the martensitic transformation increased with increasing temperature from room temperature up to 300 C, but then decreased at higher temperatures. Ferroelastic deformation of tetragonal ZrO 2 has been observed at all temperatures up to 1,000 C. At the highest temperature, only ferroelastic domain switching and dislocation slip occurred during indentation-induced deformation

  18. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

    Directory of Open Access Journals (Sweden)

    Antonio Aubry

    2016-10-01

    Full Text Available Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR and norepinephrine release within the amygdala leads to the mobilization of AMPA receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  19. Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival

    Science.gov (United States)

    Elsing, Alexandra N.; Aspelin, Camilla; Björk, Johanna K.; Bergman, Heidi A.; Himanen, Samu V.; Kallio, Marko J.; Roos-Mattjus, Pia

    2014-01-01

    Unless mitigated, external and physiological stresses are detrimental for cells, especially in mitosis, resulting in chromosomal missegregation, aneuploidy, or apoptosis. Heat shock proteins (Hsps) maintain protein homeostasis and promote cell survival. Hsps are transcriptionally regulated by heat shock factors (HSFs). Of these, HSF1 is the master regulator and HSF2 modulates Hsp expression by interacting with HSF1. Due to global inhibition of transcription in mitosis, including HSF1-mediated expression of Hsps, mitotic cells are highly vulnerable to stress. Here, we show that cells can counteract transcriptional silencing and protect themselves against proteotoxicity in mitosis. We found that the condensed chromatin of HSF2-deficient cells is accessible for HSF1 and RNA polymerase II, allowing stress-inducible Hsp expression. Consequently, HSF2-deficient cells exposed to acute stress display diminished mitotic errors and have a survival advantage. We also show that HSF2 expression declines during mitosis in several but not all human cell lines, which corresponds to the Hsp70 induction and protection against stress-induced mitotic abnormalities and apoptosis. PMID:25202032

  20. Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

    Science.gov (United States)

    Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

    2004-04-01

    Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

  1. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Directory of Open Access Journals (Sweden)

    Penny J Tricker

    2015-09-01

    Full Text Available The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defence ‘priming’ and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity’s adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  2. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Science.gov (United States)

    Tricker, Penny J

    2015-01-01

    The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defense "priming" and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity's adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  3. Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression

    Directory of Open Access Journals (Sweden)

    Francesco Rusconi

    2018-05-01

    Full Text Available Psychiatric disorders entail maladaptive processes impairing individuals’ ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress—including bullying, mobbing and abuse—, and undergoing economic crisis or chronic illnesses. In the last few years the field of epigenetics promised to understand core mechanisms of gene-environment crosstalk, contributing to get into pathogenic processes of many disorders highly influenced by stressful life conditions. However, still very little is known about mechanisms that tune gene expression to adapt to the external milieu. In this Perspective article, we discuss a set of protective, functionally convergent epigenetic processes induced by acute stress in the rodent hippocampus and devoted to the negative modulation of stress-induced immediate early genes (IEGs transcription, hindering stress-driven morphostructural modifications of corticolimbic circuitry. We also suggest that chronic stress damaging protective epigenetic mechanisms, could bias the functional trajectory of stress-induced neuronal morphostructural modification from adaptive to maladaptive, contributing to the onset of depression in vulnerable individuals. A better understanding of the epigenetic response to stress will be pivotal to new avenues of therapeutic intervention to treat depression, especially in light of limited efficacy of available antidepressant drugs.

  4. Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells.

    Science.gov (United States)

    He, Ruijun; Cui, Min; Lin, Hui; Zhao, Lei; Wang, Jiayu; Chen, Songfeng; Shao, Zengwu

    2018-04-15

    Intervertebral disc degeneration (IVDD) is thought to be the major cause of low back pain (LBP), which is still in lack of effective etiological treatment. Oxidative stress has been demonstrated to participate in the impairment of nucleus pulposus cells (NPCs). As the most important neuroendocrine hormone in biological clock regulation, melatonin (MLT) is also featured by good antioxidant effect. In this study, we investigated the effect and mechanisms of melatonin on oxidative stress-induced damage in rat NPCs. Cytotoxicity of H 2 O 2 and protecting effect of melatonin were analyzed with Cell Counting kit-8 (CCK-8). Cell apoptosis rate was detected by Annexin V-FITC/PI staining. DCFH-DA probe was used for the reactive oxygen species (ROS) detection. The mitochondrial membrane potential (MMP) changes were analyzed with JC-1 probe. Intracellular oxidation product and reductants were measured through enzymatic reactions. Extracellular matrix (ECM) and apoptosis associated proteins were analyzed with Western blot assays. Melatonin preserved cell viability of NPCs under oxidative stress. The apoptosis rate, ROS level and malonaldehyde (MDA) declined with melatonin. MLT/H 2 O 2 group showed higher activities of GSH and SOD. The fall of MMP receded and the expression of ECM protein increased with treatment of melatonin. The mitochondrial pathway of apoptosis was inhibited by melatonin. Melatonin alleviated the oxidative stress-induced apoptosis of NPCs. Melatonin could be a promising alternative in treatment of IVDD. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. A Stress-Induced Bias in the Reading of the Genetic Code in Escherichia coli

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    Adi Oron-Gottesman

    2016-11-01

    Full Text Available Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a stress-induced translation machinery (STM, composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we further characterized the STM system, finding that MazF cleaves only ACA sites located in the open reading frames of processed mRNAs, while out-of-frame ACAs are resistant. This in-frame ACA cleavage of MazF seems to depend on MazF binding to an extracellular-death-factor (EDF-like element in ribosomal protein bS1 (bacterial S1, apparently causing MazF to be part of STM ribosomes. Furthermore, due to the in-frame MazF cleavage of ACAs under stress, a bias occurs in the reading of the genetic code causing the amino acid threonine to be encoded only by its synonym codon ACC, ACU, or ACG, instead of by ACA.

  6. Evaluation of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage

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    R Sunil Kumar

    2017-01-01

    Full Text Available Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy.

  7. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  8. Effects of Cynodon dactylon on Stress-Induced Infertility in Male Rats

    Science.gov (United States)

    Chidrawar, VR; Chitme, HR; Patel, KN; Patel, NJ; Racharla, VR; Dhoraji, NC; Vadalia, KR

    2011-01-01

    Cynodon dactylon (Family: Poaceae) is known to be a tackler in Indian mythology and is offered to Lord Ganesha. It is found everywhere, even on waste land, road side, dry places, and spreads vigorously on cultivated ground. This study was carried out with an objective to test if the constituents of this plant are useful in coping stress-induced sexual In this study, we considered immobilization stress to induce male infertility and the effect of C. dactylon in restoration of the dysfunction was evaluated by considering sexual behavioral observations, sexual performance, fructose content of the seminal vesicles, epididymal sperm concentration and histopathological examinations as parameters. Treatment of rats under stress with methanolic extract of C. dactylon has shown a promising effect in overcoming stress-induced sexual dysfunction, sexual performance, fructose content, sperm concentration and its effect on accessory sexual organs and body weight. We conclude that active constituents of C. dactylon present in methanolic extract have a potent aphrodisiac and male fertility activity. PMID:21607051

  9. Finite-strain micromechanical model of stress-induced martensitic transformations in shape memory alloys

    International Nuclear Information System (INIS)

    Stupkiewicz, S.; Petryk, H.

    2006-01-01

    A micromechanical model of stress-induced martensitic transformation in single crystals of shape memory alloys is developed. This model is a finite-strain counterpart to the approach presented recently in the small-strain setting [S. Stupkiewicz, H. Petryk, J. Mech. Phys. Solids 50 (2002) 2303-2331]. The stress-induced transformation is assumed to proceed by the formation and growth of parallel martensite plates within the austenite matrix. Propagation of phase transformation fronts is governed by a rate-independent thermodynamic criterion with a threshold value for the thermodynamic driving force, including in this way the intrinsic dissipation due to phase transition. This criterion selects the initial microstructure at the onset of transformation and governs the evolution of the laminated microstructure at the macroscopic level. A multiplicative decomposition of the deformation gradient into elastic and transformation parts is assumed, with full account for the elastic anisotropy of the phases. The pseudoelastic behavior of Cu-Zn-Al single crystal in tension and compression is studied as an application of the model

  10. Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

    Science.gov (United States)

    Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

    2016-08-30

    Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.

  11. Water deficit stress-induced changes in carbon and nitrogen partitioning in Chenopodium quinoa Willd.

    Science.gov (United States)

    Bascuñán-Godoy, Luisa; Reguera, Maria; Abdel-Tawab, Yasser M; Blumwald, Eduardo

    2016-03-01

    Water deficit stress followed by re-watering during grain filling resulted in the induction of the ornithine pathway and in changes in Quinoa grain quality. The genetic diversity of Chenopodium quinoa Willd. (Quinoa) is accompanied by an outstanding environmental adaptability and high nutritional properties of the grains. However, little is known about the biochemical and physiological mechanisms associated with the abiotic stress tolerance of Quinoa. Here, we characterized carbon and nitrogen metabolic changes in Quinoa leaves and grains in response to water deficit stress analyzing their impact on the grain quality of two lowland ecotypes (Faro and BO78). Differences in the stress recovery response were found between genotypes including changes in the activity of nitrogen assimilation-associated enzymes that resulted in differences in grain quality. Both genotypes showed a common strategy to overcome water stress including the stress-induced synthesis of reactive oxygen species scavengers and osmolytes. Particularly, water deficit stress induced the stimulation of the ornithine and raffinose pathways. Our results would suggest that the regulation of C- and N partitioning in Quinoa during grain filling could be used for the improvement of the grain quality without altering grain yields.

  12. The Degradation of 14C-Glutamic Acid by L-Glutamic Acid Decarboxylase.

    Science.gov (United States)

    Dougherty, Charles M; Dayan, Jean

    1982-01-01

    Describes procedures and semi-micro reaction apparatus (carbon dioxide trap) to demonstrate how a particular enzyme (L-Glutamic acid decarboxylase) may be used to determine the site or sites of labeling in its substrate (carbon-14 labeled glutamic acid). Includes calculations, solutions, and reagents used. (Author/SK)

  13. The application of glutamic acid alpha-decarboxylase for the valorization of glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Biase, De Daniela; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2009-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of nitrogen containing bulk chemicals, thereby decreasing the dependency on fossil fuels. On the pathway from glutamic acid to a range of molecules, the

  14. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

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    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  15. Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex.

    Science.gov (United States)

    MacDowell, Karina S; Sayd, Aline; García-Bueno, Borja; Caso, Javier R; Madrigal, José L M; Leza, Juan Carlos

    2017-09-01

    Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.

  16. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway

    Science.gov (United States)

    Jung, T.W.; Lee, M.W.; Lee, Y.-J.; Kim, S.M.

    2012-01-01

    Type 2 diabetes mellitus is thought to be partially associated with endoplasmic reticulum (ER) stress toxicity on pancreatic beta cells and the result of decreased insulin synthesis and secretion. In this study, we showed that a well-known insulin sensitizer, metformin, directly protects against dysfunction and death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase activation. We also showed that exposure of NIT-1 cells to metformin (5mM) increases cellular resistance against ER stress-induced NIT-1 cell dysfunction and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on cell function and death. Metformin-mediated protective effects on ER stress-induced apoptosis were not a result of an unfolded protein response or the induced inhibitors of apoptotic proteins. In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.

  17. Introduction to the Glutamate-Glutamine Cycle.

    Science.gov (United States)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain 14 C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor. This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion but more recent research has seriously questioned this.This volume of Advances in Neurobiology is intended to provide a detailed discussion of recent developments in research aimed at delineating the functional roles of the cycle taking into account that in order for this system to work there must be a tight coupling between metabolism of glutamate in astrocytes, transfer of glutamine to neurons and de novo synthesis of glutamine in astrocytes. To understand this, knowledge about the activity and regulation of the enzymes and transporters involved in these processes is required and as can be seen from the table of contents these issues will be dealt with in detail in the individual chapters of the book.

  18. Involvement of heme oxygenase-1 expression in neuroprotection by piceatannol, a natural analog and a metabolite of resveratrol, against glutamate-mediated oxidative injury in HT22 neuronal cells.

    Science.gov (United States)

    Son, Yong; Byun, Seung Jae; Pae, Hyun-Ock

    2013-08-01

    Neuronal cell death caused by oxidative stress is common in a variety of neural diseases and can be investigated in detail in cultured HT22 neuronal cells, where the amino acid glutamate at high concentrations causes glutathione depletion by inhibition of the glutamate/cystine antiporter system, intracellular accumulation of reactive oxygen species (ROS) and eventually oxidative stress-induced neuronal cell death. Using this paradigm, we have previously reported that resveratrol (3,5,4'-trans-trihydroxystilbene) protects HT22 neuronal cells from glutamate-induced oxidative stress by inducing heme oxygenase (HO)-1 expression. Piceatannol (3,5,4',3'-trans-trihydroxystilbene), which is a hydroxylated resveratrol analog and one of the resveratrol metabolites, is estimated to exert neuroprotective effect similar to that of resveratrol. The aim of this study, thus, is to determine whether piceatannol, similarly to resveratrol, would protect HT22 neuronal cells from glutamate-induced oxidative stress. Glutamate at high concentrations induced neuronal cell death and ROS formation. Piceatannol reduced glutamate-induced cell death and ROS formation. The observed cytoprotective effect was much higher when HT22 neuronal cells were pretreated with piceatannol for 6 or 12 h prior to glutamate treatment than when pretreated for 0.5 h. Piceatannol also increased HO-1 expression and HO activity via its activation of nuclear factor-E2-related factor 2 (Nrf2). Interestingly, neuroprotective effect of piceatannol was partly (but not completely) abolished by either down-regulation of HO-1 expression or blockage of HO-1 activity. Taken together, our results suggest that piceatannol, similar to resveratrol, is capable of protecting HT22 neuronal cells against glutamate-induced cell death, at least in part, by inducing Nrf2-dependent HO-1 expression.

  19. Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

    Science.gov (United States)

    Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

    2016-05-01

    Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress

  20. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  1. Orientation dependence of stress-induced martensite formation during nanoindentation in NiTi shape memory alloys

    International Nuclear Information System (INIS)

    Laplanche, G.; Pfetzing-Micklich, J.; Eggeler, G.

    2014-01-01

    In the present work we used nanoindentation with a spherical indenter tip to study the formation of stress-induced martensite in NiTi shape memory alloys. Prior to nanoindentation, orientation imaging was performed to select austenite grains with specific crystallographic orientations, including the principal crystallographic directions [0 0 1], [1 0 1] and [1 1 1]. We studied a material where stress-induced martensite is stable at room temperature and found surface patterns with four-, two- and threefold symmetries for the [0 0 1], [1 0 1] and [1 1 1] crystallographic indentation directions, respectively. Atomic force microscopy investigations of the topography showed that the surface patterns were associated with sink-ins. The crystallographic sink-in patterns disappeared during heating, which proved their martensitic origin. Our results provide clear experimental evidence which shows that the crystallographic anisotropy of nanoindentation is governed by the crystallographic anisotropy of the stress-induced formation of martensite

  2. Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels.

    Science.gov (United States)

    Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S

    2017-07-01

    Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic

  3. Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

    Science.gov (United States)

    Xu, Jiqian; Hu, Houxiang; Chen, Bin; Yue, Rongchuan; Zhou, Zhou; Liu, Yin; Zhang, Shuang; Xu, Lei; Wang, Huan; Yu, Zhengping

    2015-01-01

    Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes. PMID:26291709

  4. Tuning stress-induced magnetic anisotropy and high frequency properties of FeCo films deposited on different curvature substrates

    International Nuclear Information System (INIS)

    Wang, Z.K.; Feng, E.X.; Liu, Q.F.; Wang, J.B.; Xue, D.S.

    2012-01-01

    It is important to control magnetic anisotropy of ferromagnetic materials. In this work, FeCo thin films are deposited on the curving substrates by electrochemical deposition to adjust the stress-induced magnetic anisotropy. The compressive stress is produced in the as-deposited films after the substrates are flattened. A simplified theoretical model of ferromagnetic resonance is utilized to measure the intrinsic magnetic anisotropy field and saturation magnetization. The results show that the stress-induced magnetic anisotropy and the resonance frequency increase with the increase of substrate curvature. The induced easy axis is perpendicular to the compressive stress direction.

  5. Stress induced martensite at the crack tip in NiTi alloys during fatigue loading

    Directory of Open Access Journals (Sweden)

    E. Sgambitterra

    2014-10-01

    Full Text Available Crack tip stress-induced phase transformation mechanisms in nickel-titanium alloys (NiTi were analyzed by Digital Image Correlation (DIC, under fatigue loads. In particular, Single Edge Crack (SEC specimens, obtained from a commercial pseudoelastic NiTi sheet, and an ad-hoc experimental setup were used, for direct measurements of the near crack tip displacement field by the DIC technique. Furthermore, a fitting procedure was developed to calculate the mode I Stress Intensity Factor (SIF, starting from the measured displacement field. Finally, cyclic tensile tests were performed at different operating temperature, in the range 298-338 K, and the evolution of the SIF was studied, which revealed a marked temperature dependence.

  6. Does stress induce (para)sex? Implications for Candida albicans evolution.

    Science.gov (United States)

    Berman, Judith; Hadany, Lilach

    2012-05-01

    Theory predicts that stress is a key factor in explaining the evolutionary role of sex in facultatively sexual organisms, including microorganisms. Organisms capable of reproducing both sexually and asexually are expected to mate more frequently when stressed, and such stress-induced mating is predicted to facilitate adaptation. Here, we propose that stress has an analogous effect on the parasexual cycle in Candida albicans, which involves alternation of generations between diploid and tetraploid cells. The parasexual cycle can generate high levels of diversity, including aneuploidy, yet it apparently occurs only rarely in nature. We review the evidence that stress facilitates four major steps in the parasexual cycle and suggest that parasex occurs much more frequently under stress conditions. This may explain both the evolutionary significance of parasex and its apparent rarity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Stress-induced phase transformation and room temperature aging in Ti-Nb-Fe alloys

    Energy Technology Data Exchange (ETDEWEB)

    Cai, S.; Schaffer, J.E. [Fort Wayne Metals Research Products Corp, 9609 Ardmore Ave., Fort Wayne, IN 46809 (United States); Ren, Y. [Advanced Photon Source, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, IL 60439 (United States)

    2017-01-05

    Room temperature deformation behavior of Ti-17Nb-1Fe and Ti-17Nb-2Fe alloys was studied by synchrotron X-ray diffraction and tensile testing. It was found that, after proper heat treatment, both alloys were able to recover a deformation strain of above 3.5% due to the Stress-induced Martensite (SIM) phase transformation. Higher Fe content increased the beta phase stability and onset stress for SIM transformation. A strong {110}{sub β} texture was produced in Ti-17Nb-2Fe compared to the {210}{sub β} texture that was observed in Ti-17Nb-1Fe. Room temperature aging was observed in both alloys, where the formation of the omega phase increased the yield strength (also SIM onset stress), and decreased the ductility and strain recovery. Other metastable beta Ti alloys may show a similar aging response and this should draw the attention of materials design engineers.

  8. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  9. Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes.

    Science.gov (United States)

    Zapolska-Downar, Danuta; Zapolski-Downar, Andrzej; Naruszewicz, Marek; Siennicka, Aldona; Krasnodebska, Barbara; Kołdziej, Blanka

    2002-11-01

    It is currently believed that oxidative stress and inflammation play a significant role in atherogenesis. Artichoke extract exhibits hypolipemic properties and contains numerous active substances with antioxidant properties in vitro. We have studied the influence of aqueous and ethanolic extracts from artichoke on intracellular oxidative stress stimulated by inflammatory mediators (TNFalpha and LPS) and ox-LDL in endothelial cells and monocytes. Oxidative stress which reflects the intracellular production of reactive oxygen species (ROS) was followed by measuring the oxidation of 2', 7'-dichlorofluorescin (DCFH) to 2', 7'-dichlorofluorescein (DCF). Agueous and ethanolic extracts from artichoke were found to inhibit basal and stimulated ROS production in endothelial cells and monocytes in dose dependent manner. In endothelial cells, the ethanolic extract (50 microg/ml) reduced ox-LDL-induced intracellular ROS production by 60% (partichoke extracts have marked protective properties against oxidative stress induced by inflammatory mediators and ox-LDL in cultured endothelial cells and monocytes.

  10. Waveguides fabricated by femtosecond laser exploiting both depressed cladding and stress-induced guiding core.

    Science.gov (United States)

    Dong, Ming-Ming; Wang, Cheng-Wei; Wu, Zheng-Xiang; Zhang, Yang; Pan, Huai-Hai; Zhao, Quan-Zhong

    2013-07-01

    We report on the fabrication of stress-induced optical channel waveguides and waveguide splitters with laser-depressed cladding by femtosecond laser. The laser beam was focused into neodymium doped phosphate glass by an objective producing a destructive filament. By moving the sample along an enclosed routine in the horizontal plane followed by a minor descent less than the filament length in the vertical direction, a cylinder with rarified periphery and densified center region was fabricated. Lining up the segments in partially overlapping sequence enabled waveguiding therein. The refractive-index contrast, near- and far-field mode distribution and confocal microscope fluorescence image of the waveguide were obtained. 1-to-2, 1-to-3 and 1-to-4 splitters were also machined with adjustable splitting ratio. Compared with traditional femtosecond laser writing methods, waveguides prepared by this approach showed controllable mode conduction, strong field confinement, large numerical aperture, low propagation loss and intact core region.

  11. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  12. The cardiokine story unfolds: ischemic stress-induced protein secretion in the heart.

    Science.gov (United States)

    Doroudgar, Shirin; Glembotski, Christopher C

    2011-04-01

    Intercellular communication depends on many factors, including proteins released via the classical or non-classical secretory pathways, many of which must be properly folded to be functional. Owing to their adverse effects on the secretion machinery, stresses such as ischemia can impair the folding of secreted proteins. Paradoxically, cells rely on secreted proteins to mount a response designed to resist stress-induced damage. This review examines this paradox using proteins secreted from the heart, cardiokines, as examples, and focuses on how the ischemic heart maintains or even increases the release of select cardiokines that regulate important cellular processes in the heart, including excitation-contraction coupling, hypertrophic growth, myocardial remodeling and stem cell function, in ways that moderate ischemic damage and enhance cardiac repair. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Kava and valerian in the treatment of stress-induced insomnia.

    Science.gov (United States)

    Wheatley, D

    2001-09-01

    Kava and valerian are herbal remedies, claimed to have anxiolytic and sedative properties respectively, without dependence potential or any appreciable side-effects. In this pilot study, 24 patients suffering from stress-induced insomnia were treated for 6 weeks with kava 120 mg daily. This was followed by 2 weeks off treatment and then, 5 having dropped out, 19 received valerian 600 mg daily for another 6 weeks. Stress was measured in three areas: social, personal and life-events; insomnia in three areas also: time to fall asleep, hours slept and waking mood. Total stress severity was significantly relieved by both compounds (p effects was 58% with each drug respectively and the 'commonest' effect was vivid dreams with valerian (16%), followed by dizziness with kava (12% ). These compounds may be useful in the treatment of stress and insomnia but further studies are required to determine their relative roles for such indications. Copyright 2001 John Wiley & Sons, Ltd.

  14. Stress induced modulation of magnetic domain diffraction of single crystalline yttrium iron garnet

    Science.gov (United States)

    Mito, Shinichiro; Yoshihara, Yuki; Takagi, Hiroyuki; Inoue, Mitsuteru

    2018-05-01

    Stress induced modulation of the diffraction angle and efficiency of the light reflected from a stripe-domain magnetic garnet was demonstrated. The spacing of the magnetic domain was changed using the inverse magnetostriction effect. The sample structure was a piezo actuator/Al reflection layer/magnetic garnet substrate. A diffraction angle between the 0th and 1st ordered light was changed from 9.12 deg. to 10.20 deg. This result indicates that the domain spacing was changed from 3.3 μm to 3.0 μm. The change of the diffraction angle was irreversible for the voltage. However, reversible, linear and continuous change of the diffraction efficiency was observed. These results could be applicable for a voltage-driven optical solid state light deflector with low power consumption and high switching speed.

  15. Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Rebecca M Shansky

    2013-04-01

    Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

  16. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

    International Nuclear Information System (INIS)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K.

    1991-01-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications

  17. Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage

    Directory of Open Access Journals (Sweden)

    Jiaxiang Shao

    2016-03-01

    Full Text Available Abstract SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.

  18. Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

    Full Text Available BACKGROUND/AIMS: Hepcidin (gene name HAMP, an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. METHODS: Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and -blotting, while prohepcidin levels in human bile were determined by ELISA. RESULTS: Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03. In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively. In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05. CONCLUSION: Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.

  19. Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.

    Science.gov (United States)

    Prusator, D K; Greenwood-Van Meerveld, B

    2016-12-01

    Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. © 2016 John Wiley & Sons Ltd.

  20. Dissecting the roles of ROCK isoforms in stress-induced cell detachment.

    Science.gov (United States)

    Shi, Jianjian; Surma, Michelle; Zhang, Lumin; Wei, Lei

    2013-05-15

    The homologous Rho kinases, ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant. Using mouse embryonic fibroblasts (MEFs) derived from ROCK1(-/-) and ROCK2(-/-) mice, we have recently reported that they play different roles in regulating doxorubicin-induced stress fiber disassembly and cell detachment: ROCK1 is involved in destabilizing the actin cytoskeleton and cell detachment, whereas ROCK2 is required for stabilizing the actin cytoskeleton and cell adhesion. Here, we present additional insights into the roles of ROCK1 and ROCK2 in regulating stress-induced impairment of cell-matrix and cell-cell adhesion. In response to doxorubicin, ROCK1(-/-) MEFs showed significant preservation of both focal adhesions and adherens junctions, while ROCK2(-/-) MEFs exhibited impaired focal adhesions but preserved adherens junctions compared with the wild-type MEFs. Additionally, inhibition of focal adhesion or adherens junction formations by chemical inhibitors abolished the anti-detachment effects of ROCK1 deletion. Finally, ROCK1(-/-) MEFs, but not ROCK2(-/-) MEFs, also exhibited preserved central stress fibers and reduced cell detachment in response to serum starvation. These results add new insights into a novel mechanism underlying the anti-detachment effects of ROCK1 deletion mediated by reduced peripheral actomyosin contraction and increased actin stabilization to promote cell-cell and cell-matrix adhesion. Our studies further support the differential roles of ROCK isoforms in regulating stress-induced loss of central stress fibers and focal adhesions as well as cell detachment.

  1. Urban stress-induced biogenic VOC emissions and SOA-forming potentials in Beijing

    Directory of Open Access Journals (Sweden)

    A. Ghirardo

    2016-03-01

    Full Text Available Trees can significantly impact the urban air chemistry by the uptake and emission of reactive biogenic volatile organic compounds (BVOCs, which are involved in ozone and particle formation. Here we present the emission potentials of "constitutive" (cBVOCs and "stress-induced" BVOCs (sBVOCs from the dominant broadleaf woody plant species in the megacity of Beijing. Based on the municipal tree census and cuvette BVOC measurements on leaf level, we built an inventory of BVOC emissions, and assessed the potential impact of BVOCs on secondary organic aerosol (SOA formation in 2005 and 2010, i.e., before and after realizing the large tree-planting program for the 2008 Olympic Games. We found that sBVOCs, such as fatty acid derivatives, benzenoids, and sesquiterpenes, constituted a significant fraction ( ∼  40 % of the total annual BVOC emissions, and we estimated that the overall annual BVOC budget may have doubled from  ∼  4.8  ×  109 g C year−1 in 2005 to  ∼  10.3  ×  109 g C year−1 in 2010 due to the increase in urban greening, while at the same time the emission of anthropogenic VOCs (AVOCs decreased by 24 %. Based on the BVOC emission assessment, we estimated the biological impact on SOA mass formation potential in Beijing. Constitutive and stress-induced BVOCs might produce similar amounts of secondary aerosol in Beijing. However, the main contributors of SOA-mass formations originated from anthropogenic sources (> 90 %. This study demonstrates the general importance to include sBVOCs when studying BVOC emissions. Although the main problems regarding air quality in Beijing still originate from anthropogenic activities, the present survey suggests that in urban plantation programs, the selection of low-emitting plant species has some potential beneficial effects on urban air quality.

  2. Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

    Science.gov (United States)

    Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

    2017-07-01

    The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

  3. Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction.

    Science.gov (United States)

    Sharp, B M

    2017-08-08

    The amygdala integrates and processes incoming information pertinent to reward and to emotions such as fear and anxiety that promote survival by warning of potential danger. Basolateral amygdala (BLA) communicates bi-directionally with brain regions affecting cognition, motivation and stress responses including prefrontal cortex, hippocampus, nucleus accumbens and hindbrain regions that trigger norepinephrine-mediated stress responses. Disruption of intrinsic amygdala and BLA regulatory neurocircuits is often caused by dysfunctional neuroplasticity frequently due to molecular alterations in local GABAergic circuits and principal glutamatergic output neurons. Changes in local regulation of BLA excitability underlie behavioral disturbances characteristic of disorders including post-traumatic stress syndrome (PTSD), autism, attention-deficit hyperactivity disorder (ADHD) and stress-induced relapse to drug use. In this Review, we discuss molecular mechanisms and neural circuits that regulate physiological and stress-induced dysfunction of BLA/amygdala and its principal output neurons. We consider effects of stress on motivated behaviors that depend on BLA; these include drug taking and drug seeking, with emphasis on nicotine-dependent behaviors. Throughout, we take a translational approach by integrating decades of addiction research on animal models and human trials. We show that changes in BLA function identified in animal addiction models illuminate human brain imaging and behavioral studies by more precisely delineating BLA mechanisms. In summary, BLA is required to promote responding for natural reward and respond to second-order drug-conditioned cues; reinstate cue-dependent drug seeking; express stress-enhanced reacquisition of nicotine intake; and drive anxiety and fear. Converging evidence indicates that chronic stress causes BLA principal output neurons to become hyperexcitable.

  4. Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats.

    Science.gov (United States)

    Rho, Sang-Gyun; Kim, Yong Sung; Choi, Suck Chei; Lee, Moon Young

    2014-03-07

    To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines. Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis. In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.

  5. Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death.

    Science.gov (United States)

    Anania, Veronica G; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R; Li, Han; Ma, Taylur P; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M; Lill, Jennie R

    2016-07-01

    Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the "unfolded protein response" (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Cellular stress induces a protective sleep-like state in C. elegans.

    Science.gov (United States)

    Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

    2014-10-20

    Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

    Science.gov (United States)

    Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

    2018-05-01

    The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

  8. Glutamate Efflux at the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Cederberg-Helms, Hans Christian; Uhd-Nielsen, Carsten; Brodin, Birger

    2014-01-01

    is well known, however endothelial cells may also play an important role through mediating brain-to-blood L-glutamate efflux. Expression of excitatory amino acid transporters has been demonstrated in brain endothelial cells of bovine, human, murine, rat and porcine origin. These can account for high...... affinity concentrative uptake of L-glutamate from the brain interstitial fluid into the capillary endothelial cells. The mechanisms in between L-glutamate uptake in the endothelial cells and L-glutamate appearing in the blood are still unclear and may involve a luminal transporter for L......-glutamate, metabolism of L-glutamate and transport of metabolites or a combination of the two. However, both in vitro and in vivo studies have demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. This review summarizes the current knowledge on the brain-to-blood L-glutamate efflux...

  9. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

  10. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    Science.gov (United States)

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. Estrogen receptor-a in the medial amygdala prevents stress-induced elevations in blood pressure in females

    Science.gov (United States)

    Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in femal...

  12. Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance

    DEFF Research Database (Denmark)

    Emanuelli, Brice; Eberlé, Delphine; Suzuki, Ryo

    2008-01-01

    , improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin...

  13. Influence of stress-induced deformations on observed water flow in fractures of the Climax Granitic Stock

    International Nuclear Information System (INIS)

    Wilder, D.G.

    1987-01-01

    Three examples of stress induced influence on fracture dominated hydrology were noted in drifts 1400 ft below surface in granite. Seepage into portions of shears near a fault zone and an adjoining drift, and mineralization of the joints were the three indicators of shear stress. Interpretation of these results are given

  14. Stress-induced martensite variant reorientation in magnetic shape memory Ni–Mn–Ga single crystal studied by neutron diffraction

    Czech Academy of Sciences Publication Activity Database

    Molnár, Peter; Šittner, Petr; Lukáš, Petr; Hannula, S.-P.; Heczko, Oleg

    2008-01-01

    Roč. 17, č. 3 (2008), 035014/1-035014/4 ISSN 0964-1726 Institutional research plan: CEZ:AV0Z10100520; CEZ:AV0Z10480505 Keywords : NiMnGa single crystal * neutron diffraction * stress induced martensite reorientation Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.743, year: 2008

  15. Influence of Glutamic Acid on the Properties of Poly(xylitol glutamate sebacate Bioelastomer

    Directory of Open Access Journals (Sweden)

    Weifu Dong

    2013-11-01

    Full Text Available In order to further improve the biocompatibility of xylitol based poly(xylitol sebacate (PXS bioelastomer, a novel kind of amino acid based poly(xylitol glutamate sebacate (PXGS has been successfully prepared in this work by melt polycondensation of xylitol, N-Boc glutamic acid and sebacic acid. Differential scanning calorimetry (DSC results indicated the glass-transition temperatures could be decreased by feeding N-Boc glutamic acid. In comparison to PXS, PXGS exhibited comparable tensile strength and much higher elongation at break at the same ratio of acid/xylitol. The introduction of glutamic acid increased the hydrophilicity and in vitro degradation rate of the bioelastomer. It was found that PXGS exhibited excellent properties, such as tensile properties, biodegradability and hydrophilicity, which could be easily tuned by altering the feeding monomer ratios. The amino groups in the PXGS polyester side chains are readily functionalized, thus the biomelastomers can be considered as potential biomaterials for biomedical application.

  16. L-glutamate Receptor In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  17. Glutamate mediated astrocytic filtering of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Gilad Wallach

    2014-12-01

    Full Text Available Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity.

  18. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  19. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Bo [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China); Zhang, Shu [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Lang, Qiaolin [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Song, Jianxia; Han, Lihui [Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Liu, Aihua, E-mail: liuah@qibebt.ac.cn [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China)

    2015-07-16

    Highlights: • E. coli surface-dispalyed Gldh exhibiting excellent enzyme activity and stability. • Sensitive amperometric biosensor for glutamate using Gldh-bacteria and MWNTs. • The glutamate biosensor exhibited high specificity and stability. - Abstract: A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP{sup +}-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP{sup +} involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current–time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM–1 mM and 2–10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N = 3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection.

  20. Strontium D-Glutamate Hexahydrate and Strontium Di(hydrogen L-glutamate) Pentahydrate

    DEFF Research Database (Denmark)

    Christgau, Stephan; Odderhede, Jette; Stahl, Kenny

    2005-01-01

    Sr(C5H7NO4)] center dot 6H(2)O, ( I), and [Sr(C5H8NO4)(2)] center dot 5H(2)O, (II), both crystallize with similar strontium - glutamate - water layers. In ( I), the neutral layers are connected through hydrogen bonds by water molecules, while in ( II), the positively charged layers are connected...... through hydrogen bonds and electrostatic interactions by interleaving layers of hydrogen glutamate anions and water molecules....

  1. DinB Upregulation Is the Sole Role of the SOS Response in Stress-Induced Mutagenesis in Escherichia coli

    Science.gov (United States)

    Galhardo, Rodrigo S.; Do, Robert; Yamada, Masami; Friedberg, Errol C.; Hastings, P. J.; Nohmi, Takehiko; Rosenberg, Susan M.

    2009-01-01

    Stress-induced mutagenesis is a collection of mechanisms observed in bacterial, yeast, and human cells in which adverse conditions provoke mutagenesis, often under the control of stress responses. Control of mutagenesis by stress responses may accelerate evolution specifically when cells are maladapted to their environments, i.e., are stressed. It is therefore important to understand how stress responses increase mutagenesis. In the Escherichia coli Lac assay, stress-induced point mutagenesis requires induction of at least two stress responses: the RpoS-controlled general/starvation stress response and the SOS DNA-damage response, both of which upregulate DinB error-prone DNA polymerase, among other genes required for Lac mutagenesis. We show that upregulation of DinB is the only aspect of the SOS response needed for stress-induced mutagenesis. We constructed two dinB(oc) (operator-constitutive) mutants. Both produce SOS-induced levels of DinB constitutively. We find that both dinB(oc) alleles fully suppress the phenotype of constitutively SOS-“off” lexA(Ind−) mutant cells, restoring normal levels of stress-induced mutagenesis. Thus, dinB is the only SOS gene required at induced levels for stress-induced point mutagenesis. Furthermore, although spontaneous SOS induction has been observed to occur in only a small fraction of cells, upregulation of dinB by the dinB(oc) alleles in all cells does not promote a further increase in mutagenesis, implying that SOS induction of DinB, although necessary, is insufficient to differentiate cells into a hypermutable condition. PMID:19270270

  2. Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni).

    Science.gov (United States)

    Dupoué, Andréaz; Angelier, Frédéric; Lourdais, Olivier; Bonnet, Xavier; Brischoux, François

    2014-02-01

    Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis. Copyright © 2013 Elsevier Inc

  3. Dependence of stress-induced omega transition and mechanical twinning on phase stability in metastable β Ti–V alloys

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.L.; Li, L.; Mei, W.; Wang, W.L.; Sun, J., E-mail: jsun@sjtu.edu.cn

    2015-09-15

    Tensile properties and deformation microstructures of a series of binary β Ti–16–22V alloys have been investigated. The results show that the plastic deformation mode changes from the plate-like stress-induced ω phase transformation with a special habit plane of (− 5052){sub ω}//(3 − 3 − 2){sub β} to (332)<113> type deformation twinning with increasing the content of vanadium in the β Ti–16–22 wt.% V alloys. The plate-like stress-induced ω phase has a special orientation relationship with the β phase matrix, i.e., [110]{sub β}//[− 12 − 10]{sub ω}, (3 − 3 − 2){sub β}//(− 5052){sub ω} and (− 55 − 4){sub β}//(30 − 31){sub ω}. The alloys plastically deformed by stress-induced ω phase transformation exhibit relatively higher yield strength than those deformed via (332)<113> type deformation twinning. It can be concluded that the stability of β phase plays a significant role in plastic deformation mode, i.e., stress-induced ω phase transformation or (332)<113> type deformation twinning, which governs the mechanical property of the β Ti–16–22 wt.% V alloys. - Highlights: • Tensile properties and deformed microstructures of β Ti–16–22V alloys were studied. • Stress-induced ω phase transformation and (332)<113> twinning occur in the alloys. • Stability of β phase plays a significant role in plastic deformation mode. • Plastic deformation mode governs the mechanical property of the alloys.

  4. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase.

    Science.gov (United States)

    Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

    2015-07-16

    A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.

    Directory of Open Access Journals (Sweden)

    Francesca Calabrese

    Full Text Available It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse.

  6. Microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Sirisansaneeyakul, Sarote; Cao, Mingfeng; Kongklom, Nuttawut; Chuensangjun, Chaniga; Shi, Zhongping; Chisti, Yusuf

    2017-09-05

    Poly-γ-glutamic acid (γ-PGA) is a natural, biodegradable and water-soluble biopolymer of glutamic acid. This review is focused on nonrecombinant microbial production of γ-PGA via fermentation processes. In view of its commercial importance, the emphasis is on L-glutamic acid independent producers (i.e. microorganisms that do not require feeding with the relatively expensive amino acid L-glutamic acid to produce γ-PGA), but glutamic acid dependent production is discussed for comparison. Strategies for improving production, reducing costs and using renewable feedstocks are discussed.

  7. Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and Reproductive Changes in Rats

    Directory of Open Access Journals (Sweden)

    David Fotsing

    2017-09-01

    Full Text Available Gladiolus dalenii is a plant commonly used in many regions of Cameroon as a cure for various diseases like headaches, epilepsy, schizophrenia, and mood disorders. Recent studies have revealed that the aqueous extract of G. dalenii (AEGD exhibited antidepressant-like properties in rats. Therefore, we hypothesized that the AEGD could protect from the stress-induced behavioral, neurochemical, and reproductive changes in rats. The objective of the present study was to elucidate the effect of the AEGD on behavioral, neurochemical, and reproductive characteristics, using female rats subjected to chronic immobilization stress. The chronic immobilization stress (3 h per day for 28 days was applied to induce female reproductive and behavioral impairments in rats. The immobilization stress was provoked in rats by putting them separately inside cylindrical restrainers with ventilated doors at ambient temperature. The plant extract was given to rats orally everyday during 28 days, 5 min before induction of stress. On a daily basis, a vaginal smear was made to assess the duration of the different phases of the estrous cycle and at the end of the 28 days of chronic immobilization stress, the rat’s behavior was assessed in the elevated plus maze. They were sacrificed by cervical disruption. The organs were weighed, the ovary histology done, and the biochemical parameters assessed. The findings of this research revealed that G. dalenii increased the entries and the time of open arm exploration in the elevated plus maze. Evaluation of the biochemical parameters levels indicated that there was a significant reduction in the corticosterone, progesterone, and prolactin levels in the G. dalenii aqueous extract treated rats compared to stressed rats whereas the levels of serotonin, triglycerides, adrenaline, cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing hormone were significantly increased in the stressed rats treated with, G. dalenii

  8. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

    Science.gov (United States)

    Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

    2014-01-01

    Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, pcortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward

  9. Ancient genes establish stress-induced mutation as a hallmark of cancer.

    Science.gov (United States)

    Cisneros, Luis; Bussey, Kimberly J; Orr, Adam J; Miočević, Milica; Lineweaver, Charles H; Davies, Paul

    2017-01-01

    Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts. We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to

  10. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  11. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle S

    2017-01-01

    concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux......., regulates the exchange of nutrients, gases, and metabolic waste products between plasma and brain interstitial fluid. It has been suggested that brain capillary endothelial cells could play an important role in L-glutamate homeostasis by mediating brain-to-blood L-glutamate efflux. Both in vitro and in vivo...

  12. Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

    Science.gov (United States)

    Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

    2017-04-01

    Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Disruption of TCA Cycle and Glutamate Metabolism Identified by Metabolomics in an In Vitro Model of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Veyrat-Durebex, Charlotte; Corcia, Philippe; Piver, Eric; Devos, David; Dangoumau, Audrey; Gouel, Flore; Vourc'h, Patrick; Emond, Patrick; Laumonnier, Frédéric; Nadal-Desbarats, Lydie; Gordon, Paul H; Andres, Christian R; Blasco, Hélène

    2016-12-01

    This study aims to develop a cellular metabolomics model that reproduces the pathophysiological conditions found in amyotrophic lateral sclerosis in order to improve knowledge of disease physiology. We used a co-culture model combining the motor neuron-like cell line NSC-34 and the astrocyte clone C8-D1A, with each over-expressing wild-type or G93C mutant human SOD1, to examine amyotrophic lateral sclerosis (ALS) physiology. We focused on the effects of mutant human SOD1 as well as oxidative stress induced by menadione on intracellular metabolism using a metabolomics approach through gas chromatography coupled with mass spectrometry (GC-MS) analysis. Preliminary non-supervised analysis by Principal Component Analysis (PCA) revealed that cell type, genetic environment, and time of culture influenced the metabolomics profiles. Supervised analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) on data from intracellular metabolomics profiles of SOD1 G93C co-cultures produced metabolites involved in glutamate metabolism and the tricarboxylic acid cycle (TCA) cycle. This study revealed the feasibility of using a metabolomics approach in a cellular model of ALS. We identified potential disruption of the TCA cycle and glutamate metabolism under oxidative stress, which is consistent with prior research in the disease. Analysis of metabolic alterations in an in vitro model is a novel approach to investigation of disease physiology.

  14. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

    Science.gov (United States)

    Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

    2016-02-01

    The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated

  15. Stress induced martensitic transformation from bcc to fcc in Ag-Zn

    International Nuclear Information System (INIS)

    Takezawa, K.; Akamatsu, R.; Marukawa, K.

    1995-01-01

    The martensitic transformation in Ag-Zn alloys of low-Zn content has been studied by optical and electron microscopic observations and by tensile tests. The β 1 phase of B2 structure transforms to the thermo-elastic martensite having 9R structure similar to Cu-based alloys upon cooling to temperature below Ms. When the β 1 phase is stretched at room temperature, the slip deformation occurs at first and then the stress-induced martensite(SIM) of wedge-like morphology forms. The SIM has the ordered fcc structure containing micro-twins. This direct transformation from bcc to fcc is a unique feature in Ag-Zn alloys. In Cu alloys, martensites of fcc structure appear only after the second transformation from the first transformation product of 9R structure. The critical stress for the martensitic transformation and a degree of order of SIM decrease as the deformation temperature rises. In Ag-Zn alloys, the martensite of disordered fcc is thermally produced also by up-quenching to a higher temperature. In the present study, the relation between martensites of ordered and disordered fcc is discussed through thermodynamical calculations. The condition for the direct transformation from bcc to fcc is also examined. (orig.)

  16. Stress-induced chemical detection using flexible metal-organic frameworks.

    Science.gov (United States)

    Allendorf, Mark D; Houk, Ronald J T; Andruszkiewicz, Leanne; Talin, A Alec; Pikarsky, Joel; Choudhury, Arnab; Gall, Kenneth A; Hesketh, Peter J

    2008-11-05

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N2 or O2. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO2. Finally, we report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes.

  17. PTR-MS as a technique for investigating stress induced emission of biogenic VOCS

    International Nuclear Information System (INIS)

    Beauchamp, J.; Hansel, A.; Wisthaler, A.; Kleist, E.; Miebach, M.; Weller, U.; Wildt, J.

    2004-01-01

    Proton-transfer-reaction mass spectrometry (PTR-MS) was used in conjunction with two GC-MS systems to investigate stress induced emissions of volatile organic compounds (VOCs) from plants. Experiments were performed in the laboratory under well defined conditions and VOC emissions were induced by ozone exposure at variable concentrations and for different durations. Tobacco (Nicotiana tabaccum cv. Bel W3) plants were used as the investigated species. This investigation demonstrated the ability of PTR-MS to provide excellent high time-resolution on-line measurements of the relevant species. The combination of the PTR-MS instrument with the two GC-MS systems (which enabled accurate compound identification) allowed for detailed investigation of the dynamics of the plants' responses to ozone stress. VOCs measured included methanol, C6- alcohols and aldehydes, methyl salicylate and sesquiterpenes. Results indicate that the temporal stress response of plants depend on the amount of stress encountered by the plant. Measurement technique and experimental results will be presented. (author)

  18. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The Arabidopsis histone chaperone FACT is required for stress-induced expression of anthocyanin biosynthetic genes.

    Science.gov (United States)

    Pfab, Alexander; Breindl, Matthias; Grasser, Klaus D

    2018-03-01

    The histone chaperone FACT is involved in the expression of genes encoding anthocyanin biosynthetic enzymes also upon induction by moderate high-light and therefore contributes to the stress-induced plant pigmentation. The histone chaperone FACT consists of the SSRP1 and SPT16 proteins and associates with transcribing RNAPII (RNAPII) along the transcribed region of genes. FACT can promote transcriptional elongation by destabilising nucleosomes in the path of RNA polymerase II, thereby facilitating efficient transcription of chromatin templates. Transcript profiling of Arabidopsis plants depleted in SSRP1 or SPT16 demonstrates that only a small subset of genes is differentially expressed relative to wild type. The majority of these genes is either up- or down-regulated in both the ssrp1 and spt16 plants. Among the down-regulated genes, those encoding enzymes of the biosynthetic pathway of the plant secondary metabolites termed anthocyanins (but not regulators of the pathway) are overrepresented. Upon exposure to moderate high-light stress several of these genes are up-regulated to a lesser extent in ssrp1/spt16 compared to wild type plants, and accordingly the mutant plants accumulate lower amounts of anthocyanin pigments. Moreover, the expression of SSRP1 and SPT16 is induced under these conditions. Therefore, our findings indicate that FACT is a novel factor required for the accumulation of anthocyanins in response to light-induction.

  20. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome.

    Science.gov (United States)

    Elsenbruch, Sigrid; Lucas, Ayscha; Holtmann, Gerald; Haag, Sebastian; Gerken, Guido; Riemenschneider, Natalie; Langhorst, Jost; Kavelaars, Annemieke; Heijnen, Cobi J; Schedlowski, Manfred

    2006-10-01

    Augmented neuroendocrine stress responses and altered immune functions may play a role in the manifestation of functional gastrointestinal (GI) disorders. We tested the hypothesis that IBS patients would demonstrate enhanced psychological and endocrine responses, as well as altered stress-induced redistribution of circulating leukocytes and lymphocytes, in response to an acute psychosocial stressor when compared with healthy controls. Responses to public speaking stress were analyzed in N = 17 IBS patients without concurrent psychiatric conditions and N = 12 healthy controls. At baseline, immediately following public speaking, and after a recovery period, state anxiety, acute GI symptoms, cardiovascular responses, serum cortisol and plasma adrenocorticotropic hormone (ACTH) were measured, and numbers of circulating leukocytes and lymphocyte subpopulations were analyzed by flow cytometry. Public speaking led to significant cardiovascular activation, a significant increase in ACTH, and a redistribution of circulating leukocytes and lymphocyte subpopulations, including significant increases in natural killer cells and cytotoxic/suppressor T cells. IBS patients demonstrated significantly greater state anxiety both at baseline and following public speaking. However, cardiovascular and endocrine responses, as well as the redistribution of circulating leukocytes and lymphocyte subpopulations after public speaking stress, did not differ for IBS patients compared with controls. In IBS patients without psychiatric comorbidity, the endocrine response as well as the circulation pattern of leukocyte subpopulations to acute psychosocial stress do not differ from healthy controls in spite of enhanced emotional responses. Future studies should discern the role of psychopathology in psychological and biological stress responses in IBS.

  1. Nucleation in stress-induced tetragonal-monoclinic transformation of constrained zirconia

    International Nuclear Information System (INIS)

    Chan, S.K.

    1992-08-01

    A theory for stress-induced tetragonal→monoclinic transformation of constrained zirconia is presented based on the assumption that when forcibly strained to a regime of absolute instability where the free energy density of the tetragonal phase has a negative curvature, the constrained tetragonal zirconia becomes unstable with respect to the development of a modulated strain pattern that will evolve into a band of twin monoclinic domains. The temperature range for such an instability, the critical size of the inclusion, the corresponding critical strain, and the periodicity of the modulation are derived in terms of parameters that can be related to the elastic stiffness coefficients of various orders of the inclusion and the shear modulus of the host matrix. An entirely different mechanism is suggested for the reverse monoclinic→tetragonal transformation because the monoclinic phase is metastable when the extrinsic stress is removed. Estimates for the parameters are inferred from a variety of experimental data for pure zirconia and the numerical values for the predicted physical quantities are obtained

  2. Effect of loading speed on the stress-induced magnetic behavior of ferromagnetic steel

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Sheng, E-mail: longtubao@zju.edu.cn; Gu, Yibin; Fu, Meili; Zhang, Da; Hu, Shengnan

    2017-02-01

    The primary goal of this research is to investigate the effect of loading speed on the stress-induced magnetic behavior of a ferromagnetic steel. Uniaxial tension tests on Q235 steel were carried out with various stress levels under different loading speeds. The variation of the magnetic signals surrounding the tested specimen was detected by a fluxgate magnetometer. The results indicated that the magnetic signal variations depended not only on the tensile load level but on the loading speed during the test. The magnetic field amplitude seemed to decrease gradually with the increase in loading speed at the same tensile load level. Furthermore, the evolution of the magnetic reversals is also related to the loading speed. Accordingly, the loading speed should be considered as one of the influencing variables in the Jies-Atherton model theory of the magnetomechanical effect. - Highlights: • Magnetic behaviors induced by different loading speeds were investigated. • Loading speed imposes strong impact on the variation of the magnetic field signals. • The magnetic field amplitude reduces gradually with the increasing loading speed. • The Jies-Atherton model theory should consider the effect of loading speed.

  3. Effect of loading speed on the stress-induced magnetic behavior of ferromagnetic steel

    International Nuclear Information System (INIS)

    Bao, Sheng; Gu, Yibin; Fu, Meili; Zhang, Da; Hu, Shengnan

    2017-01-01

    The primary goal of this research is to investigate the effect of loading speed on the stress-induced magnetic behavior of a ferromagnetic steel. Uniaxial tension tests on Q235 steel were carried out with various stress levels under different loading speeds. The variation of the magnetic signals surrounding the tested specimen was detected by a fluxgate magnetometer. The results indicated that the magnetic signal variations depended not only on the tensile load level but on the loading speed during the test. The magnetic field amplitude seemed to decrease gradually with the increase in loading speed at the same tensile load level. Furthermore, the evolution of the magnetic reversals is also related to the loading speed. Accordingly, the loading speed should be considered as one of the influencing variables in the Jies-Atherton model theory of the magnetomechanical effect. - Highlights: • Magnetic behaviors induced by different loading speeds were investigated. • Loading speed imposes strong impact on the variation of the magnetic field signals. • The magnetic field amplitude reduces gradually with the increasing loading speed. • The Jies-Atherton model theory should consider the effect of loading speed.

  4. Evaluation of Stress-Inducing Factors of Educational Environment in Hamadan Dentistry School’s Students

    Directory of Open Access Journals (Sweden)

    M. Dalband

    2007-01-01

    Full Text Available ntroduction & Objective: The aim of this study was to evaluate stressor factors of educational environment in Hamadan dental school’s students in year 2002.Materials & Methods: The study design was descriptive, cross-sectional and it was accomplished using a questionnaire which was taken from DES (dental environment stress questionnaire. According to restricted number of statistical population all members of population (154 students were evaluated as samples and this study was a survey one. Results: The results of this study indicated that most stressfull factors in dental students has been related to class work with mean score 3.18±0.83 and faculty-student relationship with mean score 3.05±0.83. Female students showed more total stress than male students (2.73 vs. 2.44. The fourth-year students had the most stress rate in all students of different years (3.05 and preclinical and clinical factors were the most stress-inducing factors of these students (3.63.Conclusion: It is concluded that the environment of Hamadan dental school and the process of education in the field of dentistry is potentially stressful. Also there is a reverse relationship between level of stress in students and their academic efficiencies.

  5. Antioxidant and neuroprotective effects of Scrophularia striata extract against oxidative stress-induced neurotoxicity.

    Science.gov (United States)

    Azadmehr, Abbas; Oghyanous, Keyvan Alizadeh; Hajiaghaee, Reza; Amirghofran, Zahra; Azadbakht, Mohammad

    2013-11-01

    In this study, the neuroprotective effect of Scrophularia striata Boiss (Scrophulariaceae) extract, a plant growing in northeastern of Iran, against oxidative stress-induced neurocytotoxicity in PC12 was evaluated. The PC12 cell line pretreated with different concentrations (10, 50, 100, and 200 μg/ml) of the extract and then treated with H2O2 to induce oxidative stress and neurotoxicity. Survival of the cells, reactive oxygen species (ROS) generation, and apoptosis were measured using MTT assay, fluorescent probe 2',7'-dichlorofluorescein diacetate, and annexin V/propidium iodide, respectively. Moreover, the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) was used to evaluate the antioxidant capacity of the plant extract. Phytochemical assay by thin layer chromatography showed that the main components, including phenolic compounds, phenyl propanoids and flavonoids, were presented in the S. striata extract. The extract in concentrations of 50-200 μg/ml protected PC12 cells from H2O2-induced toxicity. The survival of the cells at concentration of 200 μg/ml was 64 % compared to that of H2O2 alone-treated cells (48 %) (p extract also dose-dependently reduced intracellular ROS production (p extract showed antioxidative effects and decreased apoptotic cells. Collectively, these findings indicated the ability of S. striata to decrease ROS generation and cell apoptosis and also suggest the presence of the neuroprotective agents in this plant.

  6. A large-scale perspective on stress-induced alterations in resting-state networks

    Science.gov (United States)

    Maron-Katz, Adi; Vaisvaser, Sharon; Lin, Tamar; Hendler, Talma; Shamir, Ron

    2016-02-01

    Stress is known to induce large-scale neural modulations. However, its neural effect once the stressor is removed and how it relates to subjective experience are not fully understood. Here we used a statistically sound data-driven approach to investigate alterations in large-scale resting-state functional connectivity (rsFC) induced by acute social stress. We compared rsfMRI profiles of 57 healthy male subjects before and after stress induction. Using a parcellation-based univariate statistical analysis, we identified a large-scale rsFC change, involving 490 parcel-pairs. Aiming to characterize this change, we employed statistical enrichment analysis, identifying anatomic structures that were significantly interconnected by these pairs. This analysis revealed strengthening of thalamo-cortical connectivity and weakening of cross-hemispheral parieto-temporal connectivity. These alterations were further found to be associated with change in subjective stress reports. Integrating report-based information on stress sustainment 20 minutes post induction, revealed a single significant rsFC change between the right amygdala and the precuneus, which inversely correlated with the level of subjective recovery. Our study demonstrates the value of enrichment analysis for exploring large-scale network reorganization patterns, and provides new insight on stress-induced neural modulations and their relation to subjective experience.

  7. Fish can show emotional fever: stress-induced hyperthermia in zebrafish.

    Science.gov (United States)

    Rey, Sonia; Huntingford, Felicity A; Boltaña, Sebastian; Vargas, Reynaldo; Knowles, Toby G; Mackenzie, Simon

    2015-11-22

    Whether fishes are sentient beings remains an unresolved and controversial question. Among characteristics thought to reflect a low level of sentience in fishes is an inability to show stress-induced hyperthermia (SIH), a transient rise in body temperature shown in response to a variety of stressors. This is a real fever response, so is often referred to as 'emotional fever'. It has been suggested that the capacity for emotional fever evolved only in amniotes (mammals, birds and reptiles), in association with the evolution of consciousness in these groups. According to this view, lack of emotional fever in fishes reflects a lack of consciousness. We report here on a study in which six zebrafish groups with access to a temperature gradient were either left as undisturbed controls or subjected to a short period of confinement. The results were striking: compared to controls, stressed zebrafish spent significantly more time at higher temperatures, achieving an estimated rise in body temperature of about 2-4°C. Thus, zebrafish clearly have the capacity to show emotional fever. While the link between emotion and consciousness is still debated, this finding removes a key argument for lack of consciousness in fishes. © 2015 The Authors.

  8. Stress-induced endocrine response and anxiety: the effects of comfort food in rats.

    Science.gov (United States)

    Ortolani, Daniela; Garcia, Márcia Carvalho; Melo-Thomas, Liana; Spadari-Bratfisch, Regina Celia

    2014-05-01

    The long-term effects of comfort food in an anxiogenic model of stress have yet to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters in rats submitted or not to chronic unpredictable mild stress (CUMS), with access to commercial chow alone or to commercial chow and comfort food. Stress did not alter the preference for comfort food but decreased food intake. In the elevated plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open arms, as well as being more likely to enter/remain in the closed arms, than were control rats, both conditions being more pronounced in the rats given access to comfort food. In the open field test, stress decreased the time spent in the centre, independent of diet; neither stress nor diet affected the number of crossing, rearing or grooming episodes. The stress-induced increase in serum corticosterone was attenuated in rats given access to comfort food. Serum concentration of triglycerides were unaffected by stress or diet, although access to comfort food increased total cholesterol and glucose. It is concluded that CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion induced an anxiogenic profile although comfort food attenuated the endocrine stress response. The present data indicate that the combination of stress and access to comfort food, common aspects of modern life, may constitute a link among stress, feeding behavior and anxiety.

  9. Natural selection underlies apparent stress-induced mutagenesis in a bacteriophage infection model.

    Science.gov (United States)

    Yosef, Ido; Edgar, Rotem; Levy, Asaf; Amitai, Gil; Sorek, Rotem; Munitz, Ariel; Qimron, Udi

    2016-04-18

    The emergence of mutations following growth-limiting conditions underlies bacterial drug resistance, viral escape from the immune system and fundamental evolution-driven events. Intriguingly, whether mutations are induced by growth limitation conditions or are randomly generated during growth and then selected by growth limitation conditions remains an open question(1). Here, we show that bacteriophage T7 undergoes apparent stress-induced mutagenesis when selected for improved recognition of its host's receptor. In our unique experimental set-up, the growth limitation condition is physically and temporally separated from mutagenesis: growth limitation occurs while phage DNA is outside the host, and spontaneous mutations occur during phage DNA replication inside the host. We show that the selected beneficial mutations are not pre-existing and that the initial slow phage growth is enabled by the phage particle's low-efficiency DNA injection into the host. Thus, the phage particle allows phage populations to initially extend their host range without mutagenesis by virtue of residual recognition of the host receptor. Mutations appear during non-selective intracellular replication, and the frequency of mutant phages increases by natural selection acting on free phages, which are not capable of mutagenesis.

  10. Stress potentiates decision biases: A stress induced deliberation-to-intuition (SIDI model

    Directory of Open Access Journals (Sweden)

    Rongjun Yu

    2016-06-01

    Full Text Available Humans often make decisions in stressful situations, for example when the stakes are high and the potential consequences severe, or when the clock is ticking and the task demand is overwhelming. In response, a whole train of biological responses to stress has evolved to allow organisms to make a fight-or-flight response. When under stress, fast and effortless heuristics may dominate over slow and demanding deliberation in making decisions under uncertainty. Here, I review evidence from behavioral studies and neuroimaging research on decision making under stress and propose that stress elicits a switch from an analytic reasoning system to intuitive processes, and predict that this switch is associated with diminished activity in the prefrontal executive control regions and exaggerated activity in subcortical reactive emotion brain areas. Previous studies have shown that when stressed, individuals tend to make more habitual responses than goal-directed choices, be less likely to adjust their initial judgment, and rely more on gut feelings in social situations. It is possible that stress influences the arbitration between the emotion responses in subcortical regions and deliberative processes in the prefrontal cortex, so that final decisions are based on unexamined innate responses. Future research may further test this ‘stress induced deliberation-to-intuition’ (SIDI model and examine its underlying neural mechanisms.

  11. Randomized test of an implementation intention-based tool to reduce stress-induced eating.

    Science.gov (United States)

    O'Connor, Daryl B; Armitage, Christopher J; Ferguson, Eamonn

    2015-06-01

    Stress may indirectly contribute to disease (e.g. cardiovascular disease, cancer) by producing deleterious changes to diet. The purpose of this study was to test the effectiveness of a stress management support (SMS) tool to reduce stress-related unhealthy snacking and to promote stress-related healthy snacking. Participants were randomized to complete a SMS tool with instruction to link stressful situations with healthy snack alternatives (experimental) or a SMS tool without a linking instruction (control). On-line daily reports of stressors and snacking were completed for 7 days. Daily stressors were associated with unhealthy snack consumption in the control condition but not in the experimental condition. Participants highly motivated towards healthy eating consumed a greater number of healthy snacks in the experimental condition on stressful days compared to participants in the experimental condition with low and mean levels of motivation. This tool is an effective, theory driven, intervention that helps to protect against stress-induced high-calorie snack consumption.

  12. ROS-mediated abiotic stress-induced programmed cell death in plants

    Directory of Open Access Journals (Sweden)

    Veselin ePetrov

    2015-02-01

    Full Text Available During the course of their ontogenesis, plants are continuously exposed to a large variety of abiotic stress factors which can damage tissues and jeopardize the survival of the organism unless properly countered. While animals can simply escape and thus evade stressors, plants as sessile organisms have developed complex strategies to withstand them. When the intensity of a detrimental factor is high, one of the defense programs employed by plants is the induction of programmed cell death (PCD. This is an active, genetically controlled process which is initiated to isolate and remove damaged tissues thereby ensuring the survival of the organism. The mechanism of PCD induction usually includes an increase in the levels of reactive oxygen species (ROS which are utilized as mediators of the stress signal. Abiotic stress-induced PCD is not only a process of fundamental biological importance, but also of considerable interest to agricultural practice as it has the potential to significantly influence crop yield. Therefore, numerous scientific enterprises have focused on elucidating the mechanisms leading to and controlling PCD in response to adverse conditions in plants. This knowledge may help to develop novel strategies to obtain more resilient crop varieties with improved tolerance and enhanced productivity. The aim of the present review is to summarize the recent advances in research on ROS-induced PCD related to abiotic stress and the role of the organelles in the process.

  13. Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle

    Science.gov (United States)

    Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Sleeman, Mark W.; Kulkarni, Rohit N.; Musi, Nicolas; Hirshman, Michael F.; Goodyear, Laurie J.

    2013-01-01

    Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle. PMID:23695665

  14. New insights into the mechanisms of water-stress-induced cavitation in conifers.

    Science.gov (United States)

    Cochard, Hervé; Hölttä, Teemu; Herbette, Stéphane; Delzon, Sylvain; Mencuccini, Maurizio

    2009-10-01

    Cavitation resistance is a key parameter to understand tree drought tolerance but little is known about the mechanisms of air entry into xylem conduits. For conifers three mechanisms have been proposed: (1) a rupture of pit margo microfibrils, (2) a displacement of the pit torus from its normal sealing position over the pit aperture, and (3) a rupture of an air-water menisci in a pore of the pit margo. In this article, we report experimental results on three coniferous species suggesting additional mechanisms. First, when xylem segments were injected with a fluid at a pressure sufficient to aspirate pit tori and well above the pressure for cavitation induction we failed to detect the increase in sample conductance that should have been caused by torus displacement from blocking the pit aperture or by membrane rupture. Second, by injecting xylem samples with different surfactant solutions, we found a linear relation between sample vulnerability to cavitation and fluid surface tension. This suggests that cavitation in conifers could also be provoked by the capillary failure of an air-water meniscus in coherence with the prediction of Young-Laplace's equation. Within the bordered pit membrane, the exact position of this capillary seeding is unknown. The possible Achilles' heel could be the seal between tori and pit walls or holes in the torus. The mechanism of water-stress-induced cavitation in conifers could then be relatively similar to the one currently proposed for angiosperms.

  15. Cross-country differences in basal and stress-induced cortisol secretion in older adults.

    Directory of Open Access Journals (Sweden)

    Juliana N Souza-Talarico

    Full Text Available Several studies have emphasized the association between socioeconomic status (SES and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries.Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST in both populations.Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants.These findings suggest that country context may modulate cortisol secretion and could impact the population health.

  16. Mild salinity stimulates a stress-induced morphogenic response in Arabidopsis thaliana roots.

    Science.gov (United States)

    Zolla, Gaston; Heimer, Yair M; Barak, Simon

    2010-01-01

    Plant roots exhibit remarkable developmental plasticity in response to local soil conditions. It is shown here that mild salt stress stimulates a stress-induced morphogenic response (SIMR) in Arabidopsis thaliana roots characteristic of several other abiotic stresses: the proliferation of lateral roots (LRs) with a concomitant reduction in LR and primary root length. The LR proliferation component of the salt SIMR is dramatically enhanced by the transfer of seedlings from a low to a high NO3- medium, thereby compensating for the decreased LR length and maintaining overall LR surface area. Increased LR proliferation is specific to salt stress (osmotic stress alone has no stimulatory effect) and is due to the progression of more LR primordia from the pre-emergence to the emergence stage, in salt-stressed plants. In salt-stressed seedlings, greater numbers of LR primordia exhibit expression of a reporter gene driven by the auxin-sensitive DR5 promoter than in unstressed seedlings. Moreover, in the auxin transporter mutant aux1-7, the LR proliferation component of the salt SIMR is completely abrogated. The results suggest that salt stress promotes auxin accumulation in developing primordia thereby preventing their developmental arrest at the pre-emergence stage. Examination of ABA and ethylene mutants revealed that ABA synthesis and a factor involved in the ethylene signalling network also regulate the LR proliferation component of the salt SIMR.

  17. Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Xueqi; Huang, Shengbin; Yu, Qing [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States); State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yu, Haiyang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yan, Shirley ShiDu, E-mail: shidu@ku.edu [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States)

    2015-12-25

    Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.

  18. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  19. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  20. Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12 Cells

    Directory of Open Access Journals (Sweden)

    Dengke Bao

    2017-07-01

    Full Text Available Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH release when exposed to hydrogen peroxide (H2O2. The significantly-alleviated intracellular reactive oxygen species (ROS, malondialdehyde (MDA, and lipoperoxidation of the cell membrane of PC-12 cells induced by H2O2 were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GSH-Px in PC-12 cells exposed to H2O2 were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

  1. Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells.

    Science.gov (United States)

    Bao, Dengke; Wang, Jingkai; Pang, Xiaobin; Liu, Hongliang

    2017-07-06

    Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson's disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H₂O₂). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H₂O₂ were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H₂O₂ were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

  2. Stress-induced insomnia treated with kava and valerian: singly and in combination.

    Science.gov (United States)

    Wheatley, David

    2001-06-01

    Kava and valerian are herbal remedies that are claimed to have anxiolytic and sedative properties respectively, without dependence potential or any appreciable side effects. In this pilot study, 24 patients suffering from stress-induced insomnia were treated for 6 weeks with kava (LI-150), 120 mg daily. This was followed by a 2-week 'wash-out' period off treatment, and then, five patients having dropped out, 19 received valerian (LI-156), 600 mg daily, for another 6 weeks. Then there was a further 2-week period off treatment, and a final 6 weeks of treatment of these 19 patients with the two compounds combined (kava + valerian). Stress was measured in three areas: social, personal and life events; insomnia in three areas also: time to fall asleep, hours slept and waking mood. Total stress severity was significantly relieved by both compounds individually (p effects on kava, 10 (53%) on valerian and 10 (53%) on the combination. The 'commonest' effect was vivid dreams with kava + valerian (4 cases (21%)) and with valerian alone (3 cases (16%)), followed by gastric discomfort and dizziness with kava (3 cases each (3 %)). These results are considered to be extremely promising but further studies may be required to determine the relative roles of the two compounds for such indications. Copyright 2001 John Wiley & Sons, Ltd.

  3. A terrified-sound stress induced proteomic changes in adult male rat hippocampus.

    Science.gov (United States)

    Yang, Juan; Hu, Lili; Wu, Qiuhua; Liu, Liying; Zhao, Lingyu; Zhao, Xiaoge; Song, Tusheng; Huang, Chen

    2014-04-10

    In this study, we investigated the biochemical mechanisms in the adult rat hippocampus underlying the relationship between a terrified-sound induced psychological stress and spatial learning. Adult male rats were exposed to a terrified-sound stress, and the Morris water maze (MWM) has been used to evaluate changes in spatial learning and memory. The protein expression profile of the hippocampus was examined using two-dimensional gel electrophoresis (2DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and bioinformatics analysis. The data from the MWM tests suggested that a terrified-sound stress improved spatial learning. The proteomic analysis revealed that the expression of 52 proteins was down-regulated, while that of 35 proteins were up-regulated, in the hippocampus of the stressed rats. We identified and validated six of the most significant differentially expressed proteins that demonstrated the greatest stress-induced changes. Our study provides the first evidence that a terrified-sound stress improves spatial learning in rats, and that the enhanced spatial learning coincides with changes in protein expression in rat hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

    Science.gov (United States)

    Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

    2006-02-15

    We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

  5. Effect of the critical size of initial voids on stress-induced migration

    International Nuclear Information System (INIS)

    Aoyagi, Minoru

    2004-01-01

    The stress-induced migration phenomenon is one of the problems related to the reliability of metal interconnections in semiconductor devices. This phenomenon causes voids and fractures in interconnections. The basic feature of this phenomenon is vacancy migration to minute initial voids. Expanding initial voids grow into larger voids and fractures. The purpose of this work is to theoretically clarify the effects of residual thermal stress and void surface stress on the behavior of the initial voids which exist immediately after a passivation process. Using a spherical metal sample with a spherical void under external stress, vacancy absorption or emission was investigated between the void surface and the sample surface. The behavior of vacancies and atoms was also investigated in interconnections under residual thermal stress. We show that the void or sample surface becomes a vacancy sink or source, depending on the mutual relationship between the surface stress due to the surface-free energy and the residual thermal stress. We also reveal that the initial voids, which exist immediately after a passivation process, grow into larger voids and fractures when the size of the initial voids exceeds the critical size. If the size of the initial void can be controlled to below the critical size, voids and fractures do not occur

  6. Cross-country differences in basal and stress-induced cortisol secretion in older adults.

    Science.gov (United States)

    Souza-Talarico, Juliana N; Plusquellec, Pierrich; Lupien, Sonia J; Fiocco, Alexandra; Suchecki, Deborah

    2014-01-01

    Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. These findings suggest that country context may modulate cortisol secretion and could impact the population health.

  7. Water avoidance stress induces frequency through cyclooxygenase-2 expression: a bladder rat model.

    Science.gov (United States)

    Yamamoto, Keisuke; Takao, Tetsuya; Nakayama, Jiro; Kiuchi, Hiroshi; Okuda, Hidenobu; Fukuhara, Shinichiro; Yoshioka, Iwao; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

    2012-02-01

    Water avoidance stress is a potent psychological stressor and it is associated with visceral hyperalgesia, which shows degeneration of the urothelial layer mimicking interstitial cystitis. Cyclooxygenase-2 inhibitors have been recognized to ameliorate frequency both in clinical and experimental settings. We investigated the voiding pattern and cyclooxygenase-2 expression in a rat bladder model of water avoidance stress. After being subjected to water avoidance stress or a sham procedure, rats underwent metabolic cage analysis and cystometrography. Real time reverse transcription polymerase chain reaction was carried out to examine cyclooxygenase-2 messenger ribonucleic acid in bladders of rats. Protein expression of cyclooxygenase-2 was analyzed with immunohistochemistry and western blotting. Furthermore, the effects of the cyclooxygenase-2 inhibitor, etodolac, were investigated by carrying out cystometrography, immunohistochemistry and western blotting. Metabolic cage analysis and cystometrography showed significantly shorter intervals and less volume of voiding in water avoidance stress rats. Significantly higher expression of cyclooxygenase-2 messenger ribonucleic acid was verified by reverse transcription polymerase chain reaction. Immunohistochemistry and western blotting showed significantly higher cyclooxygenase-2 protein levels in water avoidance stress bladders. Furthermore, immunohistochemistry showed high cyclooxygenase-2 expression exclusively in smooth muscle cells. All water avoidance stress-induced changes were reduced by cyclooxygenase-2 inhibitor pretreatment. Chronic stress might cause frequency through cyclooxygenase-2 gene upregulation in bladder smooth muscle cells. Further study of cyclooxygenase-2 in the water avoidance stress bladder might provide novel therapeutic modalities for interstitial cystitis. © 2011 The Japanese Urological Association.

  8. Analysis of the stress-inducible transcription factor SsNAC23 in sugarcane plants

    Directory of Open Access Journals (Sweden)

    Renata Fava Ditt

    2011-08-01

    Full Text Available Stresses such as cold and drought can impair plant yield and induce a highly complex array of responses. Sugarcane (Saccharum spp. is cultivated in tropical and subtropical areas and is considered a cold-sensitive plant. We previously showed that cold stress induces the expression of several genes in in vitro sugarcane plantlets. Here we characterize one of those genes, SsNAC23, a member of the NAC family of plant-specific transcription factors, which are induced by low temperature and other stresses in several plant species. The expression of SsNAC23 was induced in sugarcane plants exposed to low temperatures (4ºC. With the aim of further understanding the regulatory network in response to stress, we used the yeast two-hybrid system to identify sugarcane proteins that interact with SsNAC23. Using SsNAC23 as bait, we screened a cDNA expression library of sugarcane plants submitted to 4ºC for 48 h. Several interacting partners were identified, including stress-related proteins, increasing our knowledge on how sugarcane plants respond to cold stress. One of these interacting partners, a thioredoxin h1, offers insights into the regulation of SsNAC23 activity.

  9. Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

    Directory of Open Access Journals (Sweden)

    Popović Nataša

    2010-01-01

    Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

  10. Genome wide transcriptional response of Saccharomyces cerevisiae to stress-induced perturbations

    Directory of Open Access Journals (Sweden)

    Hilal eTaymaz-Nikerel

    2016-02-01

    Full Text Available Cells respond to environmental and/or genetic perturbations in order to survive and proliferate. Characterization of the changes after various stimuli at different -omics levels is crucial to comprehend the adaptation of cells to changing conditions. Genome wide quantification and analysis of transcript levels, the genes affected by perturbations, extends our understanding of cellular metabolism by pointing out the mechanisms that play role in sensing the stress caused by those perturbations and related signaling pathways, and in this way guides us to achieve endeavors such as rational engineering of cells or interpretation of disease mechanisms. Saccharomyces cerevisiae as a model system has been studied in response to different perturbations and corresponding transcriptional profiles were followed either statically or/and dynamically, short- and long- term. This review focuses on response of yeast cells to diverse stress inducing perturbations including nutritional changes, ionic stress, salt stress, oxidative stress, osmotic shock, as well as to genetic interventions such as deletion and over-expression of genes. It is aimed to conclude on common regulatory phenomena that allow yeast to organize its transcriptomic response after any perturbation under different external conditions.

  11. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

    International Nuclear Information System (INIS)

    Zana, Marianna; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Szabo, Krisztina; Vetro, Agnes; Szucs, Peter; Varkonyi, Agnes; Pakaski, Magdolna; Boda, Krisztina; Rasko, Istvan; Janka, Zoltan; Kalman, Janos

    2006-01-01

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults

  12. Stress induced anisotropy in CoFeMn soft magnetic nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Leary, A. M., E-mail: leary@cmu.edu; Keylin, V.; McHenry, M. E. [Materials Science and Engineering Department, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, Pennsylvania 15213 (United States); Ohodnicki, P. R. [Functional Materials Development Division, National Energy Technology Laboratory (NETL), 626 Cochrans Mill Road, Pittsburgh, Pennsylvania 15236 (United States)

    2015-05-07

    The use of processing techniques to create magnetic anisotropy in soft magnetic materials is a well-known method to control permeability and losses. In nanocomposite materials, field annealing below the Curie temperature results in uniaxial anisotropy energies up to ∼2 kJ/m{sup 3}. Higher anisotropies up to ∼10 kJ/m{sup 3} result after annealing Fe-Si compositions under stress due to residual stress in the amorphous matrix acting on body centered cubic crystals. This work describes near zero magnetostriction Co{sub 80−x−y}Fe{sub x}Mn{sub y}Nb{sub 4}B{sub 14}Si{sub 2} soft magnetic nanocomposites, where x and y < 8 at.% with close packed crystalline grains that show stress induced anisotropies up to ∼50 kJ/m{sup 3} and improved mechanical properties with respect to Fe-Si compositions. Difference patterns measured using transmission X-ray diffraction show evidence of affine strain with respect to the stress axis.

  13. Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death

    International Nuclear Information System (INIS)

    Apostolou, Andria; Shen Yuxian; Liang Yan; Luo Jun; Fang Shengyun

    2008-01-01

    The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress that initiates the unfolded protein response (UPR). UPR activates both adaptive and apoptotic pathways, which contribute differently to disease pathogenesis. To further understand the functional mechanisms of UPR, we identified 12 commonly UPR-upregulated genes by expression microarray analysis. Here, we describe characterization of Armet/MANF, one of the 12 genes whose function was not clear. We demonstrated that the Armet/MANF protein was upregulated by various forms of ER stress in several cell lines as well as by cerebral ischemia of rat. Armet/MANF was localized in the ER and Golgi and was also a secreted protein. Silencing Armet/MANF by siRNA oligos in HeLa cells rendered cells more susceptible to ER stress-induced death, but surprisingly increased cell proliferation and reduced cell size. Overexpression of Armet/MANF inhibited cell proliferation and improved cell viability under glucose-free conditions and tunicamycin treatment. Based on its inhibitory properties for both proliferation and cell death we have demonstrated, Armet is, thus, a novel secreted mediator of the adaptive pathway of UPR

  14. Micromechanical modeling of stress-induced strain in polycrystalline Ni–Mn–Ga by directional solidification

    International Nuclear Information System (INIS)

    Zhu, Yuping; Shi, Tao; Teng, Yao

    2015-01-01

    Highlights: • A micromechanical model of directional solidification Ni–Mn–Ga is developed. • The stress–strain curves in different directions are tested. • The martensite Young’s moduli in different directions are predicted. • The macro reorientation strains in different directions are investigated. - Abstract: Polycrystalline ferromagnetic shape memory alloy Ni–Mn–Ga produced by directional solidification possess unique properties. Its compressive stress–strain behaviors in loading–unloading cycle show nonlinear and anisotropic. Based on the self-consistent theory and thermodynamics principle, a micromechanical constitutive model of polycrystalline Ni–Mn–Ga by directional solidification is developed considering the generating mechanism of the macroscopic strain and anisotropy. Then, the stress induced strains at different angles to solidification direction are calculated, and the results agree well with the experimental data. The predictive curves of martensite Young’s modulus and macro reorientation strain in different directions are investigated. It may provide theoretical guidance for the design and use of ferromagnetic shape memory alloy

  15. The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans.

    Science.gov (United States)

    Iannacone, Michael J; Beets, Isabel; Lopes, Lindsey E; Churgin, Matthew A; Fang-Yen, Christopher; Nelson, Matthew D; Schoofs, Liliane; Raizen, David M

    2017-01-17

    In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans , stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1 , which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo , is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.

  16. Mechanisms of Stress-Induced Visceral Pain: Implications in Irritable Bowel Syndrome.

    Science.gov (United States)

    Greenwood-Van Meerveld, B; Moloney, R D; Johnson, A C; Vicario, M

    2016-08-01

    Visceral pain is a term describing pain originating from the internal organs of the body and is a common feature of many disorders, including irritable bowel syndrome (IBS). Stress is implicated in the development and exacerbation of many visceral pain disorders. Recent evidence suggests that stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviours. The Young Investigator Forum at the International Society of Psychoneuroendocrinology (ISPNE) annual meeting reported experimental evidence suggesting the gut microbiota can affect the stress response to affect visceral pain. Building upon human imaging data showing abnormalities in the central processing of visceral stimuli in patients with IBS and knowledge that the amygdala plays a pivotal role in facilitating the stress axis, the latest experimental evidence supporting amygdala-mediated mechanisms in stress-induced visceral pain was reviewed. The final part of the session at ISPNE reviewed experimental evidence suggesting that visceral pain in IBS may be a result, at least in part, of afferent nerve sensitisation following increases in epithelial permeability and mucosal immune activation. © 2016 British Society for Neuroendocrinology.

  17. An Elongin-Cullin-SOCS Box Complex Regulates Stress-Induced Serotonergic Neuromodulation

    Directory of Open Access Journals (Sweden)

    Xicotencatl Gracida

    2017-12-01

    Full Text Available Neuromodulatory cells transduce environmental information into long-lasting behavioral responses. However, the mechanisms governing how neuronal cells influence behavioral plasticity are difficult to characterize. Here, we adapted the translating ribosome affinity purification (TRAP approach in C. elegans to profile ribosome-associated mRNAs from three major tissues and the neuromodulatory dopaminergic and serotonergic cells. We identified elc-2, an Elongin C ortholog, specifically expressed in stress-sensing amphid neuron dual ciliated sensory ending (ADF serotonergic sensory neurons, and we found that it plays a role in mediating a long-lasting change in serotonin-dependent feeding behavior induced by heat stress. We demonstrate that ELC-2 and the von Hippel-Lindau protein VHL-1, components of an Elongin-Cullin-SOCS box (ECS E3 ubiquitin ligase, modulate this behavior after experiencing stress. Also, heat stress induces a transient redistribution of ELC-2, becoming more nuclearly enriched. Together, our results demonstrate dynamic regulation of an E3 ligase and a role for an ECS complex in neuromodulation and control of lasting behavioral states.

  18. Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility.

    Science.gov (United States)

    West, C; Wu, R Y; Wong, A; Stanisz, A M; Yan, R; Min, K K; Pasyk, M; McVey Neufeld, K-A; Karamat, M I; Foster, J A; Bienenstock, J; Forsythe, P; Kunze, W A

    2017-01-01

    Environmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility. We have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB-1 ™ . Motility of fluid-filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes. Stress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB-1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude. Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system. © 2016 John Wiley & Sons Ltd.

  19. Selye's general adaptation syndrome: stress-induced gastro-duodenal ulceration and inflammatory bowel disease.

    Science.gov (United States)

    Fink, George

    2017-03-01

    Hans Selye in a note to Nature in 1936 initiated the field of stress research by showing that rats exposed to nocuous stimuli responded by way of a 'general adaptation syndrome' (GAS). One of the main features of the GAS was the 'formation of acute erosions in the digestive tract, particularly in the stomach, small intestine and appendix'. This provided experimental evidence for the view based on clinical data that gastro-duodenal (peptic) ulcers could be caused by stress. This hypothesis was challenged by Marshall and Warren's Nobel Prize (2005)-winning discovery of a causal association between Helicobacter pylori and peptic ulcers. However, clinical and experimental studies suggest that stress can cause peptic ulceration in the absence of H. pylori Predictably, the etiological pendulum of gastric and duodenal ulceration has swung from 'all stress' to 'all bacteria' followed by a sober realization that both factors play a role, separately as well as together. This raises the question as to whether stress and H. pylori interact, and if so, how? Stress has also been implicated in inflammatory bowel disease (IBD) and related disorders; however, there is no proof yet that stress is the primary etiological trigger for IBD. Central dopamine mechanisms seem to be involved in the stress induction of peptic ulceration, whereas activation of the sympathetic nervous system and central and peripheral corticotrophin-releasing factor appears to mediate stress-induced IBD. © 2017 Society for Endocrinology.

  20. Detection of ULF geomagnetic signals associated with seismic events in Central Mexico using Discrete Wavelet Transform

    Directory of Open Access Journals (Sweden)

    O. Chavez

    2010-12-01

    Full Text Available The geomagnetic observatory of Juriquilla Mexico, located at longitude –100.45° and latitude 20.70°, and 1946 m a.s.l., has been operational since June 2004 compiling geomagnetic field measurements with a three component fluxgate magnetometer. In this paper, the results of the analysis of these measurements in relation to important seismic activity in the period of 2007 to 2009 are presented. For this purpose, we used superposed epochs of Discrete Wavelet Transform of filtered signals for the three components of the geomagnetic field during relative seismic calm, and it was compared with seismic events of magnitudes greater than Ms > 5.5, which have occurred in Mexico. The analysed epochs consisted of 18 h of observations for a dataset corresponding to 18 different earthquakes (EQs. The time series were processed for a period of 9 h prior to and 9 h after each seismic event. This data processing was compared with the same number of observations during a seismic calm. The proposed methodology proved to be an efficient tool to detect signals associated with seismic activity, especially when the seismic events occur in a distance (D from the observatory to the EQ, such that the ratio D/ρ < 1.8 where ρ is the earthquake radius preparation zone. The methodology presented herein shows important anomalies in the Ultra Low Frequency Range (ULF; 0.005–1 Hz, primarily for 0.25 to 0.5 Hz. Furthermore, the time variance (σ2 increases prior to, during and after the seismic event in relation to the coefficient D1 obtained, principally in the Bx (N-S and By (E-W geomagnetic components. Therefore, this paper proposes and develops a new methodology to extract the abnormal signals of the geomagnetic anomalies related to different stages of the EQs.

  1. Glutamate monitoring in vitro and in vivo: recent progress in the field of glutamate biosensors

    DEFF Research Database (Denmark)

    Rieben, Nathalie Ines; Rose, Nadia Cherouati; Martinez, Karen Laurence

    2009-01-01

    is currently the most common method for in vivo glutamate sampling. However, the recent development and improvement of enzyme-based amperometric glutamate biosensors makes them a promising alternative to microdialysis for in vivo applications, as well as valuable devices for in vitro applications in basic......, and different techniques have been developed to this end. This review presents and discusses these techniques, especially the recent progress in the field of glutamate biosensors, as well as the great potential of nanotechnology in glutamate sensing. Microdialysis coupled to analytical detection techniques...... neurobiological research. Another interesting group of biosensors for glutamate are fluorescence-based glutamate biosensors, which have unsurpassed spatio-temporal resolution and are therefore important tools for investigating glutamate dynamics during signaling. Adding to this list are biosensors based on nano...

  2. Glutamate in schizophrenia: clinical and research implications.

    Science.gov (United States)

    Goff, D C; Wine, L

    1997-10-30

    The excitatory amino acids, glutamate and aspartate, are of interest to schizophrenia research because of their roles in neurodevelopment, neurotoxicity and neurotransmission. Recent evidence suggests that densities of glutamatergic receptors and the ratios of subunits composing these receptors may be altered in schizophrenia, although it is unclear whether these changes are primary or compensatory. Agents acting at the phencyclidine binding site of the NMDA receptor produce symptoms of schizophrenia in normal subjects, and precipitate relapse in patients with schizophrenia. The improvement of negative symptoms with agents acting at the glycine modulatory site of the NMDA receptor, as well as preliminary evidence that clozapine may differ from conventional neuroleptic agents in its effects on glutamatergic systems, suggest that clinical implications may follow from this model. While geriatric patients may be at increased risk for glutamate-mediated neurotoxicity, very little is known about the specific relevance of this model to geriatric patients with schizophrenia.

  3. Glutamate dehydrogenase (RocG) in Bacillus licheniformis WX-02: Enzymatic properties and specific functions in glutamic acid synthesis for poly-γ-glutamic acid production.

    Science.gov (United States)

    Tian, Guangming; Wang, Qin; Wei, Xuetuan; Ma, Xin; Chen, Shouwen

    2017-04-01

    Poly-γ-glutamic acid (γ-PGA), a natural biopolymer, is widely used in cosmetics, medicine, food, water treatment, and agriculture owing to its features of moisture sequestration, cation chelation, non-toxicity and biodegradability. Intracellular glutamic acid, the substrate of γ-PGA, is a limiting factor for high yield in γ-PGA production. Bacillus subtilis and Bacillus licheniformis are both important γ-PGA producing strains, and B. subtilis synthesizes glutamic acid in vivo using the unique GOGAT/GS pathway. However, little is known about the glutamate synthesis pathway in B. licheniformis. The aim of this work was to characterize the glutamate dehydrogenase (RocG) in glutamic acid synthesis from B. licheniformis with both in vivo and in vitro experiments. By re-directing the carbon flux distribution, the rocG gene deletion mutant WX-02ΔrocG produced intracellular glutamic acid with a concentration of 90ng/log(CFU), which was only 23.7% that of the wild-type WX-02 (380ng/log(CFU)). Furthermore, the γ-PGA yield of mutant WX-02ΔrocG was 5.37g/L, a decrease of 45.3% compared to the wild type (9.82g/L). In vitro enzymatic assays of RocG showed that RocG has higher affinity for 2-oxoglutarate than glutamate, and the glutamate synthesis rate was far above degradation. This is probably the first study to reveal the glutamic acid synthesis pathway and the specific functions of RocG in B. licheniformis. The results indicate that γ-PGA production can be enhanced through improving intracellular glutamic acid synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

    Directory of Open Access Journals (Sweden)

    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  5. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  6. EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi-Hwi; Kim, Eung-Hwi [College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Jung, Hye Seung [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Yang, Dongki [Department of Physiology, Gachon University College of Medicine, Incheon (Korea, Republic of); Park, Eun-Young, E-mail: parkey@mokpo.ac.kr [College of Pharmacy, Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam (Korea, Republic of); Jun, Hee-Sook, E-mail: hsjun@gachon.ac.kr [College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, Incheon (Korea, Republic of)

    2017-01-15

    Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H{sub 2}O{sub 2}. Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factor erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is

  7. EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

    International Nuclear Information System (INIS)

    Kim, Mi-Hwi; Kim, Eung-Hwi; Jung, Hye Seung; Yang, Dongki; Park, Eun-Young; Jun, Hee-Sook

    2017-01-01

    Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H 2 O 2 . Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factor erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is mediated by

  8. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression

    DEFF Research Database (Denmark)

    Agudelo, Leandro Z; Femenía, Teresa; Orhan, Funda

    2014-01-01

    Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which...... skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid......, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration...

  9. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

  10. Stress-induced martensitic transformations in NiTi and NiTi-TiC composites investigated by neutron diffraction

    International Nuclear Information System (INIS)

    Vaidyanathan, R.; Dunand, D.C.

    1999-01-01

    Superelastic NiTi (51.0 at.% Ni) specimens reinforced with 0, 10 and 20 vol.% TiC particles were deformed under uniaxial compression while neutron diffraction spectra were collected. The experiments yielded in-situ measurements of the thermoelastic stress-induced transformation. The evolution of austenite/martensite phase fractions and of elastic strains in the reinforcing TiC particles and the austenite matrix were obtained by Rietveld refinement during the loading cycle as the austenite transforms to martensite (and its subsequent back transformation during unloading). Phase fractions and strains are discussed in terms of load transfer in composites where the matrix undergoes a stress-induced phase transformation. (orig.)

  11. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

    Directory of Open Access Journals (Sweden)

    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  12. Retinal Pigment Epithelial Cell Culture and Cooperation of L-carnitine in Reducing Stress Induced Cellular Damage

    International Nuclear Information System (INIS)

    Shamsi, Farrukh A.; Al-Rajhi, Ali A.; Athmanathan, S.; Boulton, M.; Chaudhry, Imtiaz A.

    2006-01-01

    Purpose was to show that L-carnitine (LC) is capable of reducing non-oxidative stress in the retinal pigment epithelial cells (RPE) of the human eye. The RPE cells were cultured from donor eyes, obtained immediately after post-mortem. The interaction between bovine serum albumin (BSA) and non-oxidative (sodium hydroxide and methyl methane sulphonate) stress-inducers was observed by recording the change in the absorption profiles of the interacting molecules after incubation in light for 5 hours and after treatment with LC. The isolated and cultured RPE cells from the human eyes were treated with sodium hydroxide or methyl methane sulphonate and/or LC for 5 hours under light, and the qualitative effect on cell morphology after treatment was analyzed by staining cells with Giemsa and visualization by light microscopy. The cell morphology was also qualitatively analyzed by scanning electron microscopy (SEM). L-carnitine and stress-inducers interact with BSA and bring about changes in the spectral profile of the interacted molecules. Light microscopy as well as SEM show that the changes in the cellular morphology, induced by 100 uM concentrations of non-oxidative stress-inducers, are considerably reduced in the presence of 100 uM LC. However, L-carnitine alone does not cause any qualitative damage to the cell morphology during incubation under similar conditions. The results give a preliminary indication that LC has ability to reduce the changes brought about by the non-oxidative stress-inducers in the RPF cells in culture. (author)

  13. Axin1 up-regulated 1 accelerates stress-induced cardiomyocytes apoptosis through activating Wnt/β-catenin signaling.

    Science.gov (United States)

    Ye, Xing; Lin, Junyi; Lin, Zebin; Xue, Aimin; Li, Liliang; Zhao, Ziqin; Liu, Li; Shen, Yiwen; Cong, Bin

    2017-10-15

    Stress-induced cardiomyocyte apoptosis contributes to the pathogenesis of a variety of cardiovascular diseases, but how stress induces cardiomyocyte apoptosis remains largely unclear. The present study aims to investigate the effects of Axin1 up-regulated 1 (Axud1), a novel pro-apoptotic protein, on the cardiomyocyte survival and the underlying mechanisms. To this end, a rat model under restraint stress (RS) was established and in vitro stress-induced cardiomyocytes culture was achieved. Our data showed that Axud1 was upregulated in the rat myocardia after exposure to RS. Anti-apoptotic Bcl-2 was decreased, whereas pro-apoptotic Bax and Cleaved caspase-3 (Cc3) were increased in a time-dependent manner. The Wnt/β-catenin signaling was observed to be interestingly activated in heart undergoing RS. In addition, the treatment of norepinephrine (NE) to in vitro cardiomyocytes increased Axud1 level and induced cell apoptosis. Wnt/β-catenin signaling was consistently activated. Knockdown of Axud1 using specific siRNA blunted NE-induced cardiomyocytes apoptosis and also inactivated the Wnt/β-catenin signaling. XAV-939, an inhibitor of Wnt/β-catenin signaling, partially reversed the pro-apoptotic effect of NE. In conclusion, Axud1 accelerated stress-induced cardiomyocytes apoptosis through activation of Wnt/β-catenin signaling pathway. Our data provided novel evidence that therapeutic strategies against Axud1 or Wnt/β-catenin signaling might be promising in relation to RS-induced myocardial injury. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats.

    Science.gov (United States)

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-08-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation.

  15. Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity

    OpenAIRE

    Strahler, Jana

    2010-01-01

    Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies hav...

  16. TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors.

    Science.gov (United States)

    Choi, Juli; Kim, Ji-eun; Kim, Tae-Kyung; Park, Jin-Young; Lee, Jung-Eun; Kim, Hannah; Lee, Eun-Hwa; Han, Pyung-Lim

    2015-10-01

    Chronic stress is a potent risk factor for depression, but the mechanism by which stress causes depression is not fully understood. To investigate the molecular mechanism underlying stress-induced depression, C57BL/6 inbred mice were treated with repeated restraint to induce lasting depressive behavioral changes. Behavioral states of individual animals were evaluated using the forced swim test, which measures psychomotor withdrawals, and the U-field test, which measures sociability. From these behavioral analyses, individual mice that showed depression-like behaviors in both psychomotor withdrawal and sociability tests, and individuals that showed a resiliency to stress-induced depression in both tests were selected. Among the neuropeptides expressed in the amygdala, thyrotropin-releasing hormone (TRH) was identified as being persistently up-regulated in the basolateral amygdala (BLA) in individuals exhibiting severe depressive behaviors in the two behavior tests, but not in individuals displaying a stress resiliency. Activation of TRH receptors by local injection of TRH in the BLA in normal mice produced depressive behaviors, mimicking chronic stress effects, whereas siRNA-mediated suppression of either TRH or TRHR1 in the BLA completely blocked stress-induced depressive symptoms. The TRHR1 agonist, taltirelin, injection in the BLA increased the level of p-ERK, which mimicked the increased p-ERK level in the BLA that was induced by treatment with repeated stress. Stereotaxic injection of U0126, a potent inhibitor of the ERK pathway, within the BLA blocked stress-induced behavioral depression. These results suggest that repeated stress produces lasting depression-like behaviors via the up-regulation of TRH and TRH receptors in the BLA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dan, E-mail: danw@bjmu.edu.cn [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Liu, Jing; Wu, Baiyan [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Tu, Bo; Zhu, Weiguo [Department of Biochemistry and Molecular Biology, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Luo, Jianyuan, E-mail: jluo@som.umaryland.edu [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Department of Medical and Research Technology, School of Medicine, University of Maryland, Baltimore 21201 (United States)

    2014-04-25

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.

  18. Academic stress-induced changes in Th1- and Th2-cytokine response

    Directory of Open Access Journals (Sweden)

    Areej M. Assaf

    2017-12-01

    Full Text Available Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8 and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10 on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

  19. Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Koon-Ho Chan

    Full Text Available Beta-amyloid (Aβ neurotoxicity is important in Alzheimer's disease (AD pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T(2DM which is characterized by insulin resistance. Interestingly, T(2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance. We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y transfected with the Swedish amyloid precursor protein (Sw-APP mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK activation and enhanced nuclear factor-kappa B (NF-κB activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1 AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif and possibly 2 suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

  20. Raman spectroscopic study of acute oxidative stress induced changes in mice skeletal muscles

    Science.gov (United States)

    Sriramoju, Vidyasagar; Alimova, Alexandra; Chakraverty, Rahul; Katz, A.; Gayen, S. K.; Larsson, L.; Savage, H. E.; Alfano, R. R.

    2008-02-01

    The oxidative stress due to free radicals is implicated in the pathogenesis of tissue damage in diseases such as muscular dystrophy, Alzheimer dementia, diabetes mellitus, and mitochrondrial myopathies. In this study, the acute oxidative stress induced changes in nicotinamide adenine dinucleotides in mouse skeletal muscles are studied in vitro using Raman spectroscopy. Mammalian skeletal muscles are rich in nicotinamide adenine dinucleotides in both reduced (NADH) and oxidized (NAD) states, as they are sites of aerobic and anaerobic respiration. The relative levels of NAD and NADH are altered in certain physiological and pathological conditions of skeletal muscles. In this study, near infrared Raman spectroscopy is used to identify the molecular fingerprints of NAD and NADH in five-week-old mice biceps femoris muscles. A Raman vibrational mode of NADH is identified in fresh skeletal muscle samples suspended in buffered normal saline. In the same samples, when treated with 1% H IIO II for 5 minutes and 15 minutes, the Raman spectrum shows molecular fingerprints specific to NAD and the disappearance of NADH vibrational bands. The NAD bands after 15 minutes were more intense than after 5 minutes. Since NADH fluoresces and NAD does not, fluorescence spectroscopy is used to confirm the results of the Raman measurements. Fluorescence spectra exhibit an emission peak at 460 nm, corresponding to NADH emission wavelength in fresh muscle samples; while the H IIO II treated muscle samples do not exhibit NADH fluorescence. Raman spectroscopy may be used to develop a minimally invasive, in vivo optical biopsy method to measure the relative NAD and NADH levels in muscle tissues. This may help to detect diseases of muscle, including mitochondrial myopathies and muscular dystrophies.

  1. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

    Science.gov (United States)

    Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

    2014-12-01

    Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

  2. Academic stress-induced changes in Th1- and Th2-cytokine response.

    Science.gov (United States)

    Assaf, Areej M; Al-Abbassi, Reem; Al-Binni, Maysaa

    2017-12-01

    Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

  3. Acute stress induces selective alterations in cost/benefit decision-making.

    Science.gov (United States)

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-09-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1-3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression.

  4. Investigation of thermoelastic stresses induced at high altitudes on aircraft external fuel tanks

    Science.gov (United States)

    Mousseau, Stephanie Lynn Steber

    As composite technology has grown over the past several decades, the use of composite materials in military applications has become more feasible and widely accepted. Although composite materials provide many benefits, including strength optimization and reduced weight, damage and repair of these materials creates an additional challenge, especially when operating in a marine environment, such as on a carrier deck. This is evident within the Navy, as excessive damage often leads to the scrapping of F/A-18 External Fuel Tanks. This damage comes in many forms, the most elusive of which is delamination. Often the delamination found on the tanks is beyond repairable limits and the cause unknown, making it difficult to predict and prevent. The purpose of this investigation was to study the structure of the Navy's 330 gallon External Fuel Tanks and investigate one potential cause of delamination, stresses induced at high altitudes by cold temperatures. A stress analysis was completed using finite element software, and validation of the model was accomplished through testing of a scale model specimen. Due to the difficulties in modeling and predicting delamination, such as unknown presence of voids and understanding failure criteria, delamination was not modeled in Abaqus, rather stresses were observed and characteristics were studied to understand the potential for delamination within the layup. In addition, studies were performed to understand the effect of material properties and layup sequence on the stress distribution within the tank. Alternative design solutions are presented which could reduce the radial stresses within the tank, and recommendations are made for further study to understand the trade-offs between stress, cost, and manufacturability.

  5. Acute Stress Induces Selective Alterations in Cost/Benefit Decision-Making

    Science.gov (United States)

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-01-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1–3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression. PMID:22569506

  6. Gestational stress induces persistent depressive-like behavior and structural modifications within the postpartum nucleus accumbens

    Science.gov (United States)

    Haim, Achikam; Sherer, Morgan; Leuner, Benedetta

    2015-01-01

    Postpartum depression (PPD) is a common complication following childbirth experienced by one in every five new mothers. Pregnancy stress enhances vulnerability to PPD and has also been shown to increase depressive-like behavior in postpartum rats. Thus, gestational stress may be an important translational risk factor that can be used to investigate the neurobiological mechanisms underlying PPD. Here we examined the effects of gestational stress on depressive-like behavior during the early/mid and late postpartum periods and evaluated whether this was accompanied by altered structural plasticity in the nucleus accumbens (NAc), a brain region that has been linked to PPD. We show that early/mid (PD8) postpartum female rats exhibited more depressive-like behavior in the forced swim test as compared to late postpartum females (PD22). However, two weeks of restraint stress during pregnancy increased depressive-like behavior regardless of postpartum timepoint. In addition, dendritic length, branching, and spine density on medium spiny neurons in the NAc shell were diminished in postpartum rats that experienced gestational stress although stress-induced reductions in spine density were evident only in early/mid postpartum females. In the NAc core, structural plasticity was not affected by gestational stress but late postpartum females exhibited lower spine density and reduced dendritic length. Overall, these data not only demonstrate structural changes in the NAc across the postpartum period, they also show that postpartum depressive-like behavior following exposure to gestational stress is associated with compromised structural plasticity in the NAc and thus may provide insight into the neural changes that could contribute to PPD. PMID:25359225

  7. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  8. FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

    Science.gov (United States)

    Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

    2017-03-01

    FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Stress-induced premature senescence (SIPS)--influence of SIPS on radiotherapy.

    Science.gov (United States)

    Suzuki, Masatoshi; Boothman, David A

    2008-03-01

    Replicative senescence is a fundamental feature in normal human diploid cells and results from dysfunctional telomeres at the Hayflick cell division limit. Ionizing radiation (IR) prematurely induces the same phenotypes as replicative senescence prior to the Hayflick limit. This process is known as stress-induced premature senescence (SIPS). Since the cell cycle is irreversibly arrested in SIPS-induced cells, even if they are stimulated by various growth factors, it is thought that SIPS is a form of cell death, irreversibly eliminating replicating cells. IR-induced-focus formation of DNA repair proteins, a marker of DNA damage, is detected in SIPS as well as replicative senescent cells. Furthermore, both processes persistently induce cell cycle checkpoint mechanisms, indicating DNA damage created by ionizing radiation induces SIPS in normal cells, possibly by the same mechanisms as those occurring in replicative senescence. Interestingly, IR induces SIPS not only in normal cells, but also in tumor cells. Due to the expression of telomerase in tumor cells, telomere-dependent replicative senescence does not occur. However, SIPS is induced under certain conditions after IR exposure. Thus, cell death triggered by IR can be attributed to apoptosis or SIPS in tumor cells. However, metabolic function remains intact in SIPS-induced cancer cells, and recent studies show that senescence eliminate cells undergoing SIPS secrete various kinds of factors outside the cell, changing the microenvironment. Evidence using co-culture systems containing normal senescent stromal cells and epithelial tumor cells show that factors secreted from senescent stroma cells promote the growth of tumor epithelial cells both in vitro and in vivo. Thus, regulation of factors secreted from SIPS-induced stromal cells, as well as tumor cells, may affect radiotherapy.

  10. Stress-induced premature senescence (SIPS). Influence of SIPS on radiotherapy

    International Nuclear Information System (INIS)

    Suzuki, Masatoshi; Boothman, D.A.

    2008-01-01

    Replicative senescence is a fundamental feature in normal human diploid cells and results from dysfunctional telomeres at the Hayflick cell division limit. Ionizing radiation (IR) prematurely induces the same phenotypes as replicative senescence prior to the Hayflick limit. This process is known as stress-induced premature senescence (SIPS). Since the cell cycle is irreversibly arrested in SIPS-induced cells, even if they are stimulated by various growth factors, it is thought that SIPS is a form of cell death, irreversibly eliminating replicating cells. IR-induced-focus formation of DNA repair proteins, a marker of DNA damage, is detected in SIPS as well as replicative senescent cells. Furthermore, both processes persistently induce cell cycle checkpoint mechanisms, indicating DNA damage created by ionizing radiation induces SIPS in normal cells, possibly by the same mechanisms as those occurring in replicative senescence. Interestingly, IR induces SIPS not only in normal cells, but also in tumor cells. Due to the expression of telomerase in tumor cells, telomere-dependent replicative senescence does not occur. However, SIPS is induced under certain conditions after IR exposure. Thus, cell death triggered by IR can be attributed to apoptosis or SIPS in tumor cells. However, metabolic function remains intact in SIPS-induced cancer cells, and recent studies show that senescence eliminate cells undergoing SIPS secrete various kinds of factors outside the cell, changing the microenvironment. Evidence using co-culture systems containing normal senescent stromal cells and epithelial tumor cells show that factors secreted from senescent stroma cells promote the growth of tumor epithelial cells both in vitro and in vivo. Thus, regulation of factors secreted from SIPS-induced stromal cells, as well as tumor cells, may affect radiotherapy. (author)

  11. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

    Directory of Open Access Journals (Sweden)

    Petra eSántha

    2016-01-01

    Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

  12. Obesity decreases the oxidant stress induced by tobacco smoke in a rat model.

    Science.gov (United States)

    Montaño, Martha; Pérez-Ramos, J; Esquivel, A; Rivera-Rosales, R; González-Avila, G; Becerril, C; Checa, M; Ramos, C

    2016-09-01

    Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits. In rats with obesity, the body weight, abdominal fat, plasma triglyceride levels, glucose AUC, insulin levels, GST activity, and αV and β6 integrin expressions were amplified. The rats with emphysema had lower values of body weight, abdominal fat, plasma insulin, triglycerides and glucose AUC but higher values of plasma MDA, GPx activity, and the lung expression of the αV and β6 integrins. The combination of obesity and emphysema compared to either condition alone led to diminished body weight, abdominal fat, plasma insulin MDA levels, GPx and GST activities, and αV and β6 integrin expressions; these parameters were all previously increased by obesity. Immunostaining for MnSOD augmented in all experimental groups, but the staining for 3-NT only increased in rats treated with tobacco alone or combined with sucrose. Results showed that obesity reduces oxidant stress and integrin expression, increasing antioxidant enzyme activities; these changes seem to partly contribute to a protective mechanism of obesity against emphysema development.

  13. Role of residual stresses induced by double peening on fatigue durability of automotive leaf springs

    International Nuclear Information System (INIS)

    Scuracchio, Bruno Geoffroy; Batista de Lima, Nelson; Schön, Cláudio Geraldo

    2013-01-01

    Highlights: ► Proper choice of peening media is needed for higher fatigue strength in leaf springs. ► Optimum double-peening condition for leaf springs: 0.8 mm shot, followed by 0.3 mm. ► Fatigue life correlates with residual stress levels at the surface (up to 0.02 mm). ► Residual stress profile below 0.02 mm has no measurable effect over fatigue life. ► Failure of the investigated parts is nucleation-controlled. - Abstract: Improvement of fatigue life in parts subjected to cyclic stresses by application of mechanical surface treatment processes is already well known, both in the industry and in the academy. Dealing with automotive springs, the shot peening process becomes an essential step in manufacturing. In the case of leaf springs, however, a systematic investigation of the effect of shot peening on fatigue life is still required. The aim of the present work is to improve the knowledge on the role of shot peening in manufacturing leaf springs for vehicles, through the analysis of residual stresses by X-ray diffraction and fatigue tests on a series of samples that were subject to ten different peening schedules. Among the investigated processes, the usage of 0.8 mm diameter cast steel shot followed by a second peening with 0.3 mm diameter cast steel shot leads to optimal performance, regarding fatigue life. X-ray diffraction analysis shows that this improved performance may be attributed to residual compressive stress maintained until a depth of 0.02 mm below the surface, which directly influences fatigue crack nucleation. Residual stresses induced by shot peening in larger depths have no influence on the sample’s fatigue life

  14. Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

    2017-05-04

    Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

  15. Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia.

    Science.gov (United States)

    Ohara, Kazuyuki; Kiyotani, Yuka; Uchida, Asako; Nagasaka, Reiko; Maehara, Hiroyuki; Kanemoto, Shigeharu; Hori, Masatoshi; Ushio, Hideki

    2011-06-15

    Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102 h, respectively), significantly different from the control values (p-oryzanol abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, γ-oryzanol, GABA plus γ-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and γ-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102 h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102 h, respectively, for γ-oryzanol). Additionally, the co-administration of GABA and γ-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102 h, respectively) and was effective in an earlier phase from 30 to 54 h. The results indicate that the co-administration of GABA and γ-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress. Copyright © 2011 Elsevier GmbH. All rights reserved.

  16. Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus.

    Science.gov (United States)

    Khalaj, Leila; Nejad, Sara Chavoshi; Mohammadi, Marzieh; Zadeh, Sadaf Sarraf; Pour, Marieh Hossein; Ahmadiani, Abolhassan; Khodagholi, Fariba; Ashabi, Ghorbangol; Alamdary, Shabnam Zeighamy; Samami, Elham

    2013-08-21

    Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. It also reduced plasma corticosterone compared with the stressed animals. Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Engineering low-cadmium rice through stress-inducible expression of OXS3-family member genes.

    Science.gov (United States)

    Wang, Changhu; Guo, Weili; Cai, Xingzhe; Li, Ruyu; Ow, David W

    2018-04-21

    Cadmium (Cd) as a carcinogen poses a great threat to food security and public health through plant-derived foods such as rice, the staple for nearly half of the world's population. We have previously reported that overexpression of truncated gene fragments derived from the rice genes OsO3L2 and OsO3L3 could reduce Cd accumulation in transgenic rice. However, we did not test the full length genes due to prior work in Arabidopsis where overexpression of these genes caused seedling lethality. Here, we report on limiting the overexpression of OsO3L2 and OsO3L3 through the use of the stress- inducible promoter RD29B. However, despite generating 625 putative transformants, only 7 lines survived as T1 seedlings and only 1 line of each overexpressed OsO3L2 or OsO3L3-produced T2 progeny. The T2 homozygotes from these 2 lines showed the same effect of reducing accumulation of Cd in root and shoot as well as in T3 grain. As importantly, the concentrations of essential metals copper (Cu), iron (Fe), manganese (Mn) and zinc (Zn) were unaffected. Analysis of the expression profile suggested that low Cd accumulation may be due to high expression of OsO3L2 and OsO3L3 in the root tip region. Cellular localization of OsO3L2 and OsO3L3 indicate that they are histone H2A interacting nuclear proteins in vascular cells and especially in the root tip region. It is possible that interaction with histone H2A modifies chromatin to regulate downstream gene expression. Copyright © 2018. Published by Elsevier B.V.

  18. Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells.

    Science.gov (United States)

    Kim, Ji-Seok; Kim, Boa; Lee, Hojun; Thakkar, Sunny; Babbitt, Dianne M; Eguchi, Satoru; Brown, Michael D; Park, Joon-Young

    2015-08-01

    The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise, which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in prehypertensive individuals and that these salutary effects are, in part, mediated by shear stress-induced mitochondrial biogenesis. Circulating levels of total (CD31(+)/CD42a(-)) and activated (CD62E(+)) microparticles released by endothelial cells were significantly decreased (∼40% for both) after a 6-mo supervised aerobic exercise training program in individuals with prehypertension. In cultured human endothelial cells, laminar shear stress reduced the release of endothelial microparticles, which was accompanied by an increase in mitochondrial biogenesis through a sirtuin 1 (SIRT1)-dependent mechanism. Resveratrol, a SIRT1 activator, treatment showed similar effects. SIRT1 knockdown using small-interfering RNA completely abolished the protective effect of shear stress. Disruption of mitochondrial integrity by either antimycin A or peroxisome proliferator-activated receptor-γ coactivator-1α small-interfering RNA significantly increased the number of total, and activated, released endothelial microparticles, and shear stress restored these back to basal levels. Collectively, these data demonstrate a critical role of endothelial mitochondrial integrity in preserving endothelial homeostasis. Moreover, prolonged laminar shear stress, which is systemically elevated during aerobic exercise in the vessel wall, mitigates endothelial dysfunction by promoting

  19. Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

    Science.gov (United States)

    Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

    2015-01-01

    We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

  20. Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise.

    Science.gov (United States)

    Brooks, Steven; Brnayan, Kayla W; DeVallance, Evan; Skinner, Roy; Lemaster, Kent; Sheets, J Whitney; Pitzer, Christopher R; Asano, Shinichi; Bryner, Randall W; Olfert, I Mark; Frisbee, Jefferson C; Chantler, Paul D

    2018-05-01

    What is the central question of this study? How does chronic stress impact cerebrovascular function and does metabolic syndrome accelerate the cerebrovascular adaptations to stress? What role does exercise training have in preventing cerebrovascular changes to stress and metabolic syndrome? What is the main finding and its importance? Stressful conditions lead to pathological adaptations of the cerebrovasculature via an oxidative nitric oxide pathway, and the presence of metabolic syndrome produces a greater susceptibility to stress-induced cerebrovascular dysfunction. The results also provide insight into the mechanisms that may contribute to the influence of stress and the role of exercise in preventing the negative actions of stress on cerebrovascular function and structure. Chronic unresolvable stress leads to the development of depression and cardiovascular disease. There is a high prevalence of depression with the metabolic syndrome (MetS), but to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16-17 weeks old) following 8 weeks of unpredictable chronic mild stress (UCMS) and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean Zucker rats (LZR), UCMS decreased (28%, P stress and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

  1. Stress-induced chemical detection using flexible metal-organic frameworks.

    Energy Technology Data Exchange (ETDEWEB)

    Allendorf, Mark D.; Hesketh, Peter J. (Georgia Institute of Technology, Atlanta, GA); Gall, Kenneth A. (Georgia Institute of Technology, Atlanta, GA); Choudhury, A. (Georgia Institute of Technology, Atlanta, GA); Pikarsky, J. (Georgia Institute of Technology, Atlanta, GA); Andruszkiewicz, Leanne (Georgia Institute of Technology, Atlanta, GA); Houk, Ronald J. T.; Talin, Albert Alec (National Institute of Standards & Technology, Gaithersburg, MD)

    2009-09-01

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be efficiently converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N{sub 2} or O{sub 2}. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO{sub 2}. We also report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes. A force field model is described that successfully predicts changes in MOF properties and the uptake of gases. This model is used to predict adsorption isotherms for a number of representative compounds, including explosives, nerve agents, volatile organic compounds, and polyaromatic hydrocarbons. The results show that, as a result of relatively large heats of adsorption (> 20 kcal mol{sup -1}) in most cases, we expect an onset of adsorption by MOF as low as 10{sup -6} kPa, suggesting the potential to detect compounds such as RDX at levels as low as 10 ppb at atmospheric pressure.

  2. Sex Differences in Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Heart Disease.

    Science.gov (United States)

    Vaccarino, Viola; Wilmot, Kobina; Al Mheid, Ibhar; Ramadan, Ronnie; Pimple, Pratik; Shah, Amit J; Garcia, Ernest V; Nye, Jonathon; Ward, Laura; Hammadah, Muhammad; Kutner, Michael; Long, Qi; Bremner, J Douglas; Esteves, Fabio; Raggi, Paolo; Quyyumi, Arshed A

    2016-08-24

    Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress-induced myocardial ischemia (MSIMI). We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent (99m)Tc-sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more-adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4-fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress. Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. Body mass index and risk for mental stress induced ischemia in coronary artery disease.

    Science.gov (United States)

    Soufer, Robert; Fernandez, Antonio B; Meadows, Judith; Collins, Dorothea; Burg, Matthew M

    2016-05-19

    Acute emotionally reactive mental stress (MS) can provoke prognostically relevant deficits in cardiac function and myocardial perfusion, and chronic inflammation increases risk for this ischemic phenomenon. We have described parasympathetic withdrawal and generation of inflammatory factors in MS. Adiposity is also associated with elevated markers of chronic inflammation. High body mass index (BMI) is frequently used as a surrogate for assessment of excess adiposity, and associated with traditional CAD risk factors, and CAD mortality. BMI is also associated with autonomic dysregulation, adipose tissue derived proinflammatory cytokines, which are also attendant to emotion provoked myocardial ischemia. Thus, we sought to determine if body mass index (BMI) contributes to risk of developing myocardial ischemia provoked by mental stress. We performed a prospective interventional study in a cohort of 161 patients with stable CAD. They completed an assessment of myocardial blood flow with single photon emission computed tomography (SPECT) simultaneously during 2 conditions: laboratory mental stress and at rest. Multivariate logistic regression determined the independent contribution of BMI to the occurrence of mental-stress induced ischemia. Mean age was 65.6±9.0 years; 87.0% had a history of hypertension, and 28.6% had diabetes. Mean BMI was 30.4±4.7. Prevalence of mental stress ischemia was 39.8%. BMI was an independent predictor of mental stress ischemia, OR=1.10, 95% CI [1.01-1.18] for one-point increase in BMI and OR=1.53, 95% CI [1.06-2.21] for a 4.7 point increase in BMI (one standard deviation beyond the cohort BMI mean), p=0.025 for all. These data suggest that BMI may serve as an independent risk marker for mental stress ischemia. The factors attendant with greater BMI, which include autonomic dysregulation and inflammation, may represent pathways by which high BMI contribute to this risk and serve as a conceptual construct to replicate these findings in larger

  4. Seagrass proliferation precedes mortality during hypo-salinity events: a stress-induced morphometric response.

    Directory of Open Access Journals (Sweden)

    Catherine J Collier

    Full Text Available Halophytes, such as seagrasses, predominantly form habitats in coastal and estuarine areas. These habitats can be seasonally exposed to hypo-salinity events during watershed runoff exposing them to dramatic salinity shifts and osmotic shock. The manifestation of this osmotic shock on seagrass morphology and phenology was tested in three Indo-Pacific seagrass species, Halophila ovalis, Halodule uninervis and Zostera muelleri, to hypo-salinity ranging from 3 to 36 PSU at 3 PSU increments for 10 weeks. All three species had broad salinity tolerance but demonstrated a moderate hypo-salinity stress response--analogous to a stress induced morphometric response (SIMR. Shoot proliferation occurred at salinities <30 PSU, with the largest increases, up to 400% increase in shoot density, occurring at the sub-lethal salinities <15 PSU, with the specific salinity associated with peak shoot density being variable among species. Resources were not diverted away from leaf growth or shoot development to support the new shoot production. However, at sub-lethal salinities where shoots proliferated, flowering was severely reduced for H. ovalis, the only species to flower during this experiment, demonstrating a diversion of resources away from sexual reproduction to support the investment in new shoots. This SIMR response preceded mortality, which occurred at 3 PSU for H. ovalis and 6 PSU for H. uninervis, while complete mortality was not reached for Z. muelleri. This is the first study to identify a SIMR in seagrasses, being detectable due to the fine resolution of salinity treatments tested. The detection of SIMR demonstrates the need for caution in interpreting in-situ changes in shoot density as shoot proliferation could be interpreted as a healthy or positive plant response to environmental conditions, when in fact it could signal pre-mortality stress.

  5. Environmental enrichment reduces chronic psychosocial stress-induced anxiety and ethanol-related behaviors in mice.

    Science.gov (United States)

    Bahi, Amine

    2017-07-03

    Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

    International Nuclear Information System (INIS)

    Wu, Dan; Liu, Jing; Wu, Baiyan; Tu, Bo; Zhu, Weiguo; Luo, Jianyuan

    2014-01-01

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration

  7. Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chunfa, E-mail: chunfa.huang@case.edu [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States); Bruggeman, Leslie A. [Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States); Hydo, Lindsey M. [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Miller, R. Tyler [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States)

    2012-06-10

    The glomerular capillary wall, composed of endothelial cells, the glomerular basement membrane and the podocytes, is continually subjected to hemodynamic force arising from tractional stress due to blood pressure and shear stress due to blood flow. Exposure of glomeruli to abnormal hemodynamic force such as hyperfiltration is associated with glomerular injury and progressive renal disease, and the conversion of mechanical stimuli to chemical signals in the regulation of the process is poorly understood in podocytes. By examining DNA fragmentation, apoptotic nuclear changes and cytochrome c release, we found that shear stress induced cell apoptosis in cultured podocytes. Meanwhile, podocytes exposed to shear stress also stimulated c-Src phosphorylation, phospholipase D (PLD) activation and mammalian target of rapamycin (mTOR) signaling. Using the antibodies against c-Src, PLD{sub 1}, and PLD{sub 2} to perform reciprocal co-immunoprecipitations and in vitro PLD activity assay, our data indicated that c-Src interacted with and activated PLD{sub 1} but not PLD{sub 2}. The inhibition of shear stress-induced c-Src phosphorylation by PP{sub 2} (a specific inhibitor of c-Src kinase) resulted in reduced PLD activity. Phosphatidic acid, produced by shear stress-induced PLD activation, stimulated mTOR signaling, and caused podocyte hypertrophy and apoptosis.

  8. Evaluation on the Pharmacological Effect of Traditional Chinese Medicine SiJunZiTang on Stress-Induced Peptic Ulcers

    Directory of Open Access Journals (Sweden)

    Chiu-Mei Chen

    2013-01-01

    Full Text Available Purpose. To explore the effects of SiJunZiTang (SJZT on central neurotransmitters and the inhibition of HCl hypersecretion, along with the role of the vagus nerve. From this, the effects of SJZT and its constituent ingredients on inhibiting stress-induced peptic ulcers will be determined. Methods. Methods used to determine SJZT's effectiveness included (1 measuring the antipeptic ulcer effects of varying combinations of the constituents of SJZT; (2 evaluations of monoamine (MA level in the brain; and (3 measuring the effects of longer-term SJZT treatment. Results. Comparing the control and experimental groups where the rats’ vagus nerves were not cut after taking SJZT orally (500 mg/kg and 1000 mg/kg, the volume of enterogastric juice, free HCl and total acidity all reduce dose-dependently. The group administered SJZT at 1000 mg/kg showed significant reductions (P<0.05. For the experimental groups where the vagus nerves were cut, a comparison with the control group suggests that the group receiving SJZT (500 mg/kg orally for 21 days demonstrated a cure rate of 34.53%. Conclusion. The results display a correlation between the therapeutic effects of SJZT on stress-induced peptic ulcers and central neurotransmitter levels. Further to this, SJZT can inhibit the hypersecretion of HCl in the stomach, thus inhibiting stress-induced peptic ulcers.

  9. Evaluation on the Pharmacological Effect of Traditional Chinese Medicine SiJunZiTang on Stress-Induced Peptic Ulcers.

    Science.gov (United States)

    Chen, Chiu-Mei; Lee, Chien-Ying; Lin, Po-Jung; Hsieh, Chin-Lang; Shih, Hung-Che

    2013-01-01

    Purpose. To explore the effects of SiJunZiTang (SJZT) on central neurotransmitters and the inhibition of HCl hypersecretion, along with the role of the vagus nerve. From this, the effects of SJZT and its constituent ingredients on inhibiting stress-induced peptic ulcers will be determined. Methods. Methods used to determine SJZT's effectiveness included (1) measuring the antipeptic ulcer effects of varying combinations of the constituents of SJZT; (2) evaluations of monoamine (MA) level in the brain; and (3) measuring the effects of longer-term SJZT treatment. Results. Comparing the control and experimental groups where the rats' vagus nerves were not cut after taking SJZT orally (500 mg/kg and 1000 mg/kg), the volume of enterogastric juice, free HCl and total acidity all reduce dose-dependently. The group administered SJZT at 1000 mg/kg showed significant reductions (P cure rate of 34.53%. Conclusion. The results display a correlation between the therapeutic effects of SJZT on stress-induced peptic ulcers and central neurotransmitter levels. Further to this, SJZT can inhibit the hypersecretion of HCl in the stomach, thus inhibiting stress-induced peptic ulcers.

  10. The obesity-induced transcriptional regulator TRIP-Br2 mediates visceral fat endoplasmic reticulum stress-induced inflammation.

    Science.gov (United States)

    Qiang, Guifen; Kong, Hyerim Whang; Fang, Difeng; McCann, Maximilian; Yang, Xiuying; Du, Guanhua; Blüher, Matthias; Zhu, Jinfang; Liew, Chong Wee

    2016-04-25

    The intimate link between location of fat accumulation and metabolic disease risk and depot-specific differences is well established, but how these differences between depots are regulated at the molecular level remains largely unclear. Here we show that TRIP-Br2 mediates endoplasmic reticulum (ER) stress-induced inflammatory responses in visceral fat. Using in vitro, ex vivo and in vivo approaches, we demonstrate that obesity-induced circulating factors upregulate TRIP-Br2 specifically in visceral fat via the ER stress pathway. We find that ablation of TRIP-Br2 ameliorates both chemical and physiological ER stress-induced inflammatory and acute phase response in adipocytes, leading to lower circulating levels of inflammatory cytokines. Using promoter assays, as well as molecular and pharmacological experiments, we show that the transcription factor GATA3 is responsible for the ER stress-induced TRIP-Br2 expression in visceral fat. Taken together, our study identifies molecular regulators of inflammatory response in visceral fat that-given that these pathways are conserved in humans-might serve as potential therapeutic targets in obesity.

  11. Stress-induced cytokinin synthesis increases drought tolerance through the coordinated regulation of carbon and nitrogen assimilation in rice.

    Science.gov (United States)

    Reguera, Maria; Peleg, Zvi; Abdel-Tawab, Yasser M; Tumimbang, Ellen B; Delatorre, Carla A; Blumwald, Eduardo

    2013-12-01

    The effects of water deficit on carbon and nitrogen metabolism were investigated in flag leaves of wild-type and transgenic rice (Oryza sativa japonica 'Kitaake') plants expressing ISOPENTENYLTRANSFERASE (IPT; encoding the enzyme that mediates the rate-limiting step in cytokinin synthesis) under the control of P(SARK), a maturation- and stress-induced promoter. While the wild-type plants displayed inhibition of photosynthesis and nitrogen assimilation during water stress, neither carbon nor nitrogen assimilation was affected by stress in the transgenic P(SARK)::IPT plants. In the transgenic plants, photosynthesis was maintained at control levels during stress and the flag leaf showed increased sucrose (Suc) phosphate synthase activity and reduced Suc synthase and invertase activities, leading to increased Suc contents. The sustained carbon assimilation in the transgenic P(SARK)::IPT plants was well correlated with enhanced nitrate content, higher nitrate reductase activity, and sustained ammonium contents, indicating that the stress-induced cytokinin synthesis in the transgenic plants played a role in maintaining nitrate acquisition. Protein contents decreased and free amino acids increased in wild-type plants during stress, while protein content was preserved in the transgenic plants. Our results indicate that the stress-induced cytokinin synthesis in the transgenic plants promoted sink strengthening through a cytokinin-dependent coordinated regulation of carbon and nitrogen metabolism that facilitates an enhanced tolerance of the transgenic plants to water deficit.

  12. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  13. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    International Nuclear Information System (INIS)

    Srisuttee, Ratakorn; Koh, Sang Seok; Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae; Jhun, Byung Hak; Horio, Yoshiyuki; Chung, Young-Hwa

    2012-01-01

    Highlights: ► Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. ► Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. ► Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. ► Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of β-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  14. Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

    Science.gov (United States)

    Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

    2015-11-13

    The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

    Science.gov (United States)

    Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

    2015-01-01

    Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

  16. Post-traumatic and stress-induced osteolysis of the distal clavicle: MR imaging findings in 17 patients

    International Nuclear Information System (INIS)

    Puente, R. de la; Boutin, R.D.; Theodorou, D.J.; Hooper, A.; Resnick, D.; Schweitzer, M.

    1999-01-01

    Objective. To describe the MR imaging findings in patients with osteolysis of the distal clavicle and to compare the MR imaging appearance of clavicular osteolysis following acute injury with that related to chronic stress. Design and patients. MR imaging examinations were reviewed in 17 patients (14 men, 3 women; ages 16-55 years) with the diagnosis of post-traumatic or stress-induced osteolysis of the clavicle. A history of a single direct injury was present in seven patients and a history of weight-lifting, participation in sports, or repetitive microtrauma was present in 10 patients. Results. MR imaging showed edema in the distal clavicle in 17 patients and, of these, eight also had edema in the acromion. The edema was most evident in STIR and fat-suppressed T2-weighted pulse sequences. Other findings about the acromioclavicular (AC) joint were prominence of the joint capsule in 14, joint fluid in eight, cortical irregularity in 12, and bone fragmentation in six patients. No differences in the MR imaging features of post-traumatic and stress-induced osteolysis of the distal clavicle were observed. Conclusion. Post-traumatic and stress-induced osteolysis of the distal clavicle have similar appearances on MR imaging, the most common and conspicuous MR imaging feature being increased T2 signal intensity in the distal clavicle. (orig.)

  17. Post-traumatic and stress-induced osteolysis of the distal clavicle: MR imaging findings in 17 patients

    Energy Technology Data Exchange (ETDEWEB)

    Puente, R. de la [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States)]|[Servicio de Radioloxia, CXH Cristal Pinor, Ourense (Spain); Boutin, R.D. [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States)]|[Department of Radiology, Veterans Affairs Medical Center, San Diego, CA (United States); Theodorou, D.J.; Hooper, A.; Resnick, D. [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States); Schweitzer, M. [Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA (United States)

    1999-04-01

    Objective. To describe the MR imaging findings in patients with osteolysis of the distal clavicle and to compare the MR imaging appearance of clavicular osteolysis following acute injury with that related to chronic stress. Design and patients. MR imaging examinations were reviewed in 17 patients (14 men, 3 women; ages 16-55 years) with the diagnosis of post-traumatic or stress-induced osteolysis of the clavicle. A history of a single direct injury was present in seven patients and a history of weight-lifting, participation in sports, or repetitive microtrauma was present in 10 patients. Results. MR imaging showed edema in the distal clavicle in 17 patients and, of these, eight also had edema in the acromion. The edema was most evident in STIR and fat-suppressed T2-weighted pulse sequences. Other findings about the acromioclavicular (AC) joint were prominence of the joint capsule in 14, joint fluid in eight, cortical irregularity in 12, and bone fragmentation in six patients. No differences in the MR imaging features of post-traumatic and stress-induced osteolysis of the distal clavicle were observed. Conclusion. Post-traumatic and stress-induced osteolysis of the distal clavicle have similar appearances on MR imaging, the most common and conspicuous MR imaging feature being increased T2 signal intensity in the distal clavicle. (orig.) With 5 figs., 1 tab., 19 refs.

  18. Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72.

    Science.gov (United States)

    Lancaster, Graeme I; Febbraio, Mark A

    2005-01-01

    The heat shock proteins are a family of highly conserved proteins with critical roles in maintaining cellular homeostasis and in protecting the cell from stressful conditions. While the critical intracellular roles of heat shock proteins are undisputed, evidence suggests that the cell possess the necessary machinery to actively secrete specific heat shock proteins in response to cellular stress. In this review, we firstly discuss the evidence that physical exercise induces the release of heat shock protein 72 from specific tissues in humans. Importantly, it appears as though this release is the result of an active secretory process, as opposed to non-specific processes such as cell lysis. Next we discuss recent in vitro evidence that has identified a mechanistic basis for the observation that cellular stress induces the release of a specific subset of heat shock proteins. Importantly, while the classical protein secretory pathway does not seem to be involved in the stress-induced release of HSP72, we discuss the evidence that lipid-rafts and exosomes are important mediators of the stress-induced release of HSP72.

  19. Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

    Science.gov (United States)

    Izgut-Uysal, Vecihe Nimet; Acar, Nuray; Birsen, Ilknur; Ozcan, Filiz; Ozbey, Ozlem; Soylu, Hakan; Avci, Sema; Tepekoy, Filiz; Akkoyunlu, Gokhan; Yucel, Gultekin; Ustunel, Ismail

    2018-04-01

    The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. [Determination of glutamic acid in biological material by capillary electrophoresis].

    Science.gov (United States)

    Narezhnaya, E; Krukier, I; Avrutskaya, V; Degtyareva, A; Igumnova, E A

    2015-01-01

    The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy.

  1. Glutamate. Its applications in food and contribution to health.

    Science.gov (United States)

    Jinap, S; Hajeb, P

    2010-08-01

    This article reviews application of glutamate in food and its benefits and role as one of the common food ingredients used. Monosodium glutamate is one of the most abundant naturally occurring amino acids which frequently added as a flavor enhancer. It produced a unique taste that cannot be provided by other basic taste (saltiness, sourness, sweetness and bitterness), referred to as a fifth taste (umami). Glutamate serves some functions in the body as well, serving as an energy source for certain tissues and as a substrate for glutathione synthesis. Glutamate has the potential to enhance food intake in older individuals and dietary free glutamate evoked a visceral sensation from the stomach, intestine and portal vein. Small quantities of glutamate used in combination with a reduced amount of table salt during food preparation allow for far less salt to be used during and after cooking. Because glutamate is one of the most intensely studied food ingredients in the food supply and has been found safe, the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization and World Health Organization placed it in the safest category for food additives. Despite a widespread belief that glutamate can elicit asthma, migraine headache and Chinese Restaurant Syndrome (CRS), there are no consistent clinical data to support this claim. In addition, findings from the literature indicate that there is no consistent evidence to suggest that individuals may be uniquely sensitive to glutamate. 2010 Elsevier Ltd. All rights reserved.

  2. Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission

    DEFF Research Database (Denmark)

    Frigerio, Francesca; Karaca, Melis; De Roo, Mathias

    2012-01-01

    Glutamate dehydrogenase (GDH), encoded by GLUD1, participates in the breakdown and synthesis of glutamate, the main excitatory neurotransmitter. In the CNS, besides its primary signaling function, glutamate is also at the crossroad of metabolic and neurotransmitter pathways. Importance of brain GDH...... was questioned here by generation of CNS-specific GDH-null mice (CnsGlud1(-/-)); which were viable, fertile and without apparent behavioral problems. GDH immunoreactivity as well as enzymatic activity were absent in Cns-Glud1(-/-) brains. Immunohistochemical analyses on brain sections revealed that the pyramidal...... oxidative catabolism of glutamate in astrocytes, showing that GDH is required for Krebs cycle pathway. As revealed by NMR studies, brain glutamate levels remained unchanged, whereas glutamine levels were increased. This pattern was favored by up-regulation of astrocyte-type glutamate and glutamine...

  3. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

    OpenAIRE

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-01-01

    AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown.

  4. Inhibitory effect of the Kampo medicinal formula Yokukansan on acute stress-induced defecation in rats

    Directory of Open Access Journals (Sweden)

    Kanada Y

    2018-04-01

    inhibit spontaneous contraction. Conclusion: These results suggested that YKS influences stress-induced defecation and that increased OT secretion may be a mechanism underlying this phenomenon. Keywords: Yokukansan, oxytocin, irritable bowel syndrome, acute stress, corticosterone, Kampo medicine

  5. Can mesenchymal stem cells reverse chronic stress-induced impairment of lung healing following traumatic injury?

    Science.gov (United States)

    Gore, Amy V; Bible, Letitia E; Livingston, David H; Mohr, Alicia M; Sifri, Ziad C

    2015-04-01

    One week following unilateral lung contusion (LC), rat lungs demonstrate full histologic recovery. When animals undergo LC plus the addition of chronic restraint stress (CS), wound healing is significantly delayed. Mesenchymal stem cells (MSCs) are pluripotent cells capable of immunomodulation, which have been the focus of much research in wound healing and tissue regeneration. We hypothesize that the addition of MSCs will improve wound healing in the setting of CS. Male Sprague-Dawley rats (n = 6-7 per group) were subjected to LC/CS with or without the injection of MSCs. MSCs were given as a single intravenous dose of 5 × 10 cells in 1 mL Iscove's Modified Dulbecco's Medium at the time of LC. Rats were subjected to 2 hours of restraint stress on Days 1 to 6 following LC. Seven days following injury, rats were sacrificed, and the lungs were examined for histologic evidence of wound healing using a well-established histologic lung injury score (LIS) to grade injury. LIS examines inflammatory cells/high-power field (HPF) averaged over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with scores ranging from 0 (normal) to 11 (highly damaged). Peripheral blood was analyzed by flow cytometry for the presence of T-regulatory (C4CD25FoxP3) cells. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). As previously shown, 7 days following isolated LC, LIS has returned to 0.83 (0.41), with a subscore of zero for inflammatory cells/HPF. The addition of CS results in an LIS of 4.4 (2.2), with a subscore of 1.9 (0.7) for inflammatory cells/HPF. Addition of MSC to LC/CS decreased LIS to 1.7 (0.8), with a subscore of zero for inflammatory cells/HPF. Furthermore, treatment of animals undergoing LC/CS with MSCs increased the %T-regulatory cells by 70% in animals undergoing LC/CS alone (12.9% [2.4]% vs. 6.2% [1.3%]). Stress-induced impairment of wound healing is reversed by the addition of MSCs given

  6. Effect of Escitalopram on Mental Stress-Induced Myocardial Ischemia: The Results of the REMIT Trial

    Science.gov (United States)

    Jiang, Wei; Velazquez, Eric J.; Kuchibhatla, Maragatha; Samad, Zainab; Boyle, Stephen H.; Kuhn, Cynthia; Becker, Richard C.; Ortel, Thomas L.; Williams, Redford B.; Rogers, Joseph G.; O’Connor, Christopher

    2015-01-01

    Importance Mental-stress-induced myocardial ischemia (MSIMI) is an intermediate surrogate endpoint representing the pathophysiological link between psychosocial risk factors and adverse outcomes of coronary heart disease (CHD). However, pharmacological interventions aimed at reducing MSIMI have not been well studied. Objective To examine the effects of 6 weeks of escitalopram treatment vs. placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. Design, Setting, and Participants The REMIT study is a randomized, double-blind, placebo-controlled trial of patients with clinically stable CHD and laboratory MSIMI. Enrollment occurred from 7/24/2007–8/24/2011 at a tertiary medical center. Interventions Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg with titration to 20 mg/day in 3 weeks) or placebo over 6 weeks. Main Outcome Measure Occurrence of MSIMI, defined as (1) development or worsening of regional wall motion abnormality; (2) left ventricular ejection fraction reduction ≥8%; and/or (3) horizontal or downsloping ST-segment depression ≥1mm in ≥2 leads lasting for ≥3 consecutive beats during ≥1 of 3 mental tasks. Results 127 participants were randomized to escitalopram (n=64) or placebo (n=63); 112 (96.1%) completed endpoint assessments (n=56 in each arm). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4 to 43.0]) had absence of MSIMI during the 3 mental stressors compared with patients taking placebo (17.5% [95% CI, 10.4 to 24.5]) based on unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (OR=2.62 [95% CI, 1.06 to 6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6 to 55.0]) than in patients receiving placebo (52.5% [95% CI, 43.3 to 61.7]), compared with baseline escitalopram (49.2% [95% CI, 39.9 to

  7. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    Science.gov (United States)

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes.

  8. High susceptibility of activated lymphocytes to oxidative stress-induced cell death

    Directory of Open Access Journals (Sweden)

    Giovanna R. Degasperi

    2008-03-01

    Full Text Available The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.O presente estudo demonstra que linfócitos ativados de baço de ratos portadores do tumor de Walker 256 são mais susceptíveis à morte celular necrótica induzida por tert-butil hidroperóxido (t-BOOH in vitro quando comparados aos controles. O quelante de ferro e antioxidante deferoxamina, o quelante intracelular de Ca2+ BAPTA, o antagonista de canal de Ca2+ nifedipina ou o inibidor da transição de permeabilidade mitocondrial ciclosporina-A, mas não o inibidor de calcineurina FK-506, inibiram de maneira similar a morte celular induzida por t-BOOH em linfócitos ativados e controles. Os linfócitos ativados apresentaram redução do potencial de membrana mitocondrial induzida por t-BOOH num mecanismo sensível a ciclosporina-A. Nossos resultados indicam que o aumento da concentração de Ca2+ citosólico em linfócitos ativados aumenta a susceptibilidade dos mesmos à morte celular induzida por estresse oxidativo, num mecanismo envolvendo a participação do poro de transição de permeabilidade mitocondrial.

  9. Study of fracture and stress-induced morphological instabilities in polymeric materials

    Science.gov (United States)

    Sabouri-Ghomi, Mohsen

    We study the phenomena of fracture in polymers at the molecular and continuum level. At a molecular level, we study the failure of polymer/polymer interfaces. Our main focus is on a specific mode of failure known as chain pull-out fracture, which is common to weak adhesive junctions, and polymer blends and mixtures. In the case of the interface between incompatible polymers, reinforcement is achieved by adding a block copolymer to the interface. We introduce a microscopic model based on Brownian dynamics to investigate the effect of the polymerization index N, of the block connector chain, on fracture toughness of such reinforced polymeric junctions. We consider the mushroom regime, where connector chains are grafted with low surface density, for the case of large pulling velocity. We find that for short chains the interface fracture toughness depends linearly on the polymerization index N of the connector chains, while for longer chains the dependence becomes N 3/2. We propose a scaling argument, based on the geometry of the initial configuration, that accounts for both short and long chains and the crossover between them. At the continuum level, we study the pattern selection mechanism of finger-like crack growth phenomena in gradient driven growth problems in general, and the structure of stress-induced morphological instabilities in crazing of polymer glasses in particular. We simulate solidification in a narrow channel through the use of a phase-field model with an adaptive grid. By tuning a dimensionless parameter, the Peclet number, we show a continuous crossover from a free dendrite at high Peclet numbers to anisotropic viscous fingering at low Peclet numbers. At low Peclet numbers we find good agreement between our results, theoretical predictions, and experiment, providing the first quantitative test of solvability theory for anisotropic viscous fingers. For high undercoolings, we find new phenomena, a solid forger which satisfies stability and

  10. Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

    OpenAIRE

    Cheng, Yuyan; Pardo, Marta; de Souza Armini, Rubia; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S.; Beurel, Eleonore

    2016-01-01

    Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6 to 12 hr after stress. A 24 hr prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine...

  11. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 2

    International Nuclear Information System (INIS)

    Wilke, A.; Simon, O.; Bergner, H.

    1984-01-01

    40 rats with a body weight of 100 g received 7 semisynthetic diets with different contents of glutamic acid and one diet contained whole-egg. A L-amino acid mixture corresponding to the pattern of egg protein was the protein source of the semisynthetic diets. Glutamic acid was supplemented succesively from 0 to 58 mol-% of the total amino acid content. On the 8th day of the experimental feeding the animals were labelled by subcutaneous injection of 14 C-glutamic acid. Subsequently the CO 2 and the 14 CO 2 excretion were measured for 24 hours. In this period 64 to 68 % of the injected radioactivity were recovered as 14 CO 2 . The curve pattern of 14 CO 2 excretion indicates two different processes of 14 CO 2 formation. One characterizing the direct degradation of glutamic acid to CO 2 with a high rate constant and a second one with a lower rate constant characterizing the 14 CO 2 formation via metabolites of glutamic acid. 77 % of the total 14 CO 2 excretion in 24 hours resulted from the direct oxidation of glutamic acid and 23 % from the oxidation of intermediates. When 14 CO 2 formation was measured 10 to 24 hours after injection of 14 C-glutamic acid a positive correlation to the content of glutamic acid in the diet was observed. The intestinal tissue contributes considerably to the catabolization of glutamic acid, however, there seems to exist an upper limit for this capacity. (author)

  12. Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

    Science.gov (United States)

    Zhou, Yuan-Yuan; Wanner, Natalie J; Xiao, Ying; Shi, Xuan-Zheng; Jiang, Xing-Hong; Gu, Jian-Guo; Xu, Guang-Yin

    2012-01-01

    AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague-Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P

  13. Effect of biotin on transcription levels of key enzymes and glutamate efflux in glutamate fermentation by Corynebacterium glutamicum.

    Science.gov (United States)

    Cao, Yan; Duan, Zuoying; Shi, Zhongping

    2014-02-01

    Biotin is an important factor affecting the performance of glutamate fermentation by biotin auxotrophic Corynebacterium glutamicum and glutamate is over-produced only when initial biotin content is controlled at suitable levels or initial biotin is excessive but with Tween 40 addition during fermentation. The transcription levels of key enzymes at pyruvate, isocitrate and α-ketoglutarate metabolic nodes, as well as transport protein (TP) of glutamate were investigated under the conditions of varied biotin contents and Tween 40 supplementation. When biotin was insufficient, the genes encoding key enzymes and TP were down-regulated in the early production phase, in particular, the transcription level of isocitrate dehydrogenase (ICDH) which was only 2% of that of control. Although the cells' morphology transformation and TP level were not affected, low transcription level of ICDH led to lower final glutamate concentration (64 g/L). When biotin was excessive, the transcription levels of key enzymes were at comparable levels as those of control with ICDH as an exception, which was only 3-22% of control level throughout production phase. In this case, little intracellular glutamate accumulation (1.5 mg/g DCW) and impermeable membrane resulted in non glutamate secretion into broth, even though the quantity of TP was more than 10-folds of control level. Addition of Tween 40 when biotin was excessive stimulated the expression of all key enzymes and TP, intracellular glutamate content was much higher (10-12 mg/g DCW), and final glutamate concentration reached control level (75-80 g/L). Hence, the membrane alteration and TP were indispensable in glutamate secretion. Biotin and Tween 40 influenced the expression level of ICDH and glutamate efflux, thereby influencing glutamate production.

  14. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 3

    International Nuclear Information System (INIS)

    Simon, O.; Wilke, A.; Bergner, H.

    1984-01-01

    Mal rats received during a 8 days experimental feeding period diets with different contents in glutamic acid. The daily feed intake was restricted to the energy maintenance level of 460 kJ/kg/sup 0.75/. The diet contained a mixture of L-amino acids corresponding to the pattern of egg protein except glutamic acid. Glutamic acid was added successively at 10 levels (0 to 14.8 % of dry matter) and the resulting diets were fed to groups of 4 animals each. At the end of the experimental feeding period 14 C- and 15 N-labelled glutamic acid were applied by intragastric infusion. CO 2 and 14 CO 2 excretion was measured during the following 4 hours and the urinary N and 15 N excretion during the following 24 hours. The CO 2 excretion decreased from 53 to 44 mmol CO 2 /100g body weight with increasing levels of dietary glutamic acid. This change seems to result from the increasing proportion of amino acids as an energetic fuel. While the amount of oxidized glutamic acid increased with increasing supplements of glutamic acid the relative 14 CO 2 excretion decreased from 57 to 48 % of the applied radioactivity. The urinary 15 N excretion during 24 hours was 31 % of the given amount of 15 N if no glutamic acid was included in the diet. This proportion increased successively up to 52 % in the case of the highest supply of glutamic acid. Because the total N excretion increased at the same extent as the 15 N excretion a complete mixing of the NH 2 groups resulting from glutamic acid due to desamination with the ammonia pool was assumed. No correlation between glutamic acid content of the diet and specific radioactivity of CO 2 or atom-% 15 N excess of urinary N was observed. (author)

  15. 78 FR 76321 - Monosodium Glutamate From China and Indonesia

    Science.gov (United States)

    2013-12-17

    ... (Preliminary)] Monosodium Glutamate From China and Indonesia Determinations On the basis of the record \\1... injured by reason of imports from China and Indonesia of monosodium glutamate, provided for in subheading... United States at less than fair value (LTFV) and subsidized by the Governments of China and Indonesia. \\1...

  16. Surface grafting of poly(L-glutamates). 3. Block copolymerization

    NARCIS (Netherlands)

    Wieringa, RH; Siesling, EA; Werkman, PJ; Vorenkamp, EJ; Schouten, AJ

    2001-01-01

    This paper describes for the first time the synthesis of surface-grafted AB-block copolypeptides, consisting of poly(gamma -benzyl L-glutamate) (PBLG) as the A-block and poly(gamma -methyl L-glutamate) (PMLG) as the B-block. Immobilized primary amine groups of (,gamma -aminopropyl)triethoxysilane

  17. Brain microdialysis of GABA and glutamate : What does it signify?

    NARCIS (Netherlands)

    Timmerman, W; Westerink, B.H.C.

    1997-01-01

    Microdialysis has become a frequently used method to study extracellular levels of GABA and glutamate in the central nervous system. However, the fact that the major part of GABA and glutamate as measured by microdialysis does not fulfill the classical criteria for exocytotic release questions the

  18. Microscopic picture of the aqueous solvation of glutamic acid

    NARCIS (Netherlands)

    Leenders, E.J.M.; Bolhuis, P.G.; Meijer, E.J.

    2008-01-01

    We present molecular dynamics simulations of glutamic acid and glutamate solvated in water, using both density functional theory (DFT) and the Gromos96 force field. We focus on the microscopic aspects of the solvation−particularly on the hydrogen bond structures and dynamics−and investigate the

  19. probing the cob(ii)alamin conductor hypothesis with glutamate ...

    African Journals Online (AJOL)

    dell

    Glutamate mutase activity was also demonstrated upon incubation of GlmS and E with 3',5'- ... overproduced in E.coli (Huhta et al. 2001,. Huhta et ..... Biochemistry. 37: 9704-9715. Buckel W 2001 Unusual enzymes involved in five pathways of glutamate fermentation. Appl. Microbiol. Biotechnol. 57: 263-273. Buckel W and ...

  20. Is glutamate involved in transient lower esophageal sphincter relaxations?

    NARCIS (Netherlands)

    Hirsch, D. P.; Tytgat, G. N. J.; Boeckxstaens, G. E. E.

    2002-01-01

    Glutamate is an important excitatory amino acid and plays a major role in brain stem neurotransmission. Although the effect of glutamate on esophaoreal motility is well studied, its role in the triggering of transient lower esophageal sphincter relaxations (TLESRs) remains to be determined.

  1. Some Properties of Glutamate Dehydrogenase from the Marine Red ...

    African Journals Online (AJOL)

    Keywords: ammonia assimilation, glutamate dehydrogenase, GDH, Gracilaria sordida, red alga, enzyme activity. Glutamate dehydrogenases (GDH, EC ... Anabolic functions could be assimilation of ammonia released during photorespiration and synthesis of N-rich transport compounds. Western Indian Ocean Journal of ...

  2. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13...

  3. Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells.

    Science.gov (United States)

    Liu, Qian; Sun, Shanquan; Yu, Wei; Jiang, Jin; Zhuo, Fei; Qiu, Guoping; Xu, Shiye; Jiang, Xuli

    2015-04-01

    Long non-coding RNAs (lncRNAs), a recently discovered class of non-coding genes, are transcribed throughout the genome. Emerging evidence suggests that lncRNAs may be involved in modulating various aspects of tumor biology, including regulating gene activity in response to external stimuli or DNA damage. No data are available regarding the expression of lncRNAs during genotoxic stress-induced apoptosis and/or necrosis in human glioma cells. In this study, we detected a change in the expression of specific candidate lncRNAs (neat1, GAS5, TUG1, BC200, Malat1, MEG3, MIR155HG, PAR5, and ST7OT1) during DNA damage-induced apoptosis in human glioma cell lines (U251 and U87) using doxorubicin (DOX) and resveratrol (RES). We also detected the expression pattern of these lncRNAs in human glioma cell lines under necrosis induced using an increased dose of DOX. Our results reveal that the lncRNA expression patterns are distinct between genotoxic stress-induced apoptosis and necrosis in human glioma cells. The sets of lncRNA expressed during genotoxic stress-induced apoptosis were DNA-damaging agent-specific. Generally, MEG3 and ST7OT1 are up-regulated in both cell lines under apoptosis induced using both agents. The induction of GAS5 is only clearly detected during DOX-induced apoptosis, whereas the up-regulation of neat1 and MIR155HG is only found during RES-induced apoptosis in both cell lines. However, TUG1, BC200 and MIR155HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. In conclusion, our findings suggest that the distinct regulation of lncRNAs may possibly involve in the process of cellular defense against genotoxic agents.

  4. Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jiamin Li

    2018-02-01

    Full Text Available Background/Aims: Endothelial-mesenchymal transition (EndMT has been shown to take part in the generation and progression of diverse diseases, involving a series of changes leading to a loss of their endothelial characteristics and an acquirement of properties typical of mesenchymal cells. Low-intensity pulsed ultrasound (LIPUS is a new therapeutic option that has been successfully used in fracture healing. However, whether LIPUS can inhibit oxidative stress-induced endothelial cell damages through inhibiting EndMT remained unknown. This study aimed to investigate the protective effects of LIPUS against oxidative stress-induced endothelial cell damages and the underlying mechanisms. Methods: EndMT was induced by H2O2 (100 µm for seven days. Human aortic endothelial cells (HAECs were exposed to H2O2 with or without LIPUS treatment for seven days. The expression of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA were analyzed. The levels of total and phosphorylated PI3K and AKT proteins were detected by Western Blot analysis. Cell chemotaxis was determined by wound healing and transwell assay. Results: LIPUS relieved EndMT by decreasing ROS accumulation and increasing activation of the PI3K signaling cascade. LIPUS alleviated the migration of EndMT-derived mesenchymal-like cells through reducing extracellular matrix (ECM deposition that is associated with matrix metallopeptidase (MMP proteolytic activity and collagen production. Conclusion: LIPUS produces cytoprotective effects against oxidative injuries to endothelial cells through suppressing the oxidative stress-induced EndMT, activating the PI3K/AKT pathway under oxidative stress, and limiting cell migration and excessive ECM deposition.

  5. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  6. True or false? Memory is differentially affected by stress-induced cortisol elevations and sympathetic activity at consolidation and retrieval.

    Science.gov (United States)

    Smeets, Tom; Otgaar, Henry; Candel, Ingrid; Wolf, Oliver T

    2008-11-01

    Adrenal stress hormones released in response to acute stress may yield memory-enhancing effects when released post-learning and impairing effects at memory retrieval, especially for emotional memory material. However, so far these differential effects of stress hormones on the various memory phases for neutral and emotional memory material have not been demonstrated within one experiment. This study investigated whether, in line with their effects on true memory, stress and stress-induced adrenal stress hormones affect the encoding, consolidation, and retrieval of emotional and neutral false memories. Participants (N=90) were exposed to a stressor before encoding, during consolidation, before retrieval, or were not stressed and then were subjected to neutral and emotional versions of the Deese-Roediger-McDermott word list learning paradigm. Twenty-four hours later, recall of presented words (true recall) and non-presented critical lure words (false recall) was assessed. Results show that stress exposure resulted in superior true memory performance in the consolidation stress group and reduced true memory performance in the retrieval stress group compared to the other groups, predominantly for emotional words. These memory-enhancing and memory-impairing effects were strongly related to stress-induced cortisol and sympathetic activity measured via salivary alpha-amylase levels. Neutral and emotional false recall, on the other hand, was neither affected by stress exposure, nor related to cortisol and sympathetic activity following stress. These results demonstrate the importance of stress-induced hormone-related activity in enhancing memory consolidation and in impairing memory retrieval, in particular for emotional memory material.

  7. Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

    Science.gov (United States)

    Takahashi, L K; Kalin, N H

    1991-08-30

    Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

  8. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    Science.gov (United States)

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    International Nuclear Information System (INIS)

    Yoshida, Go J.; Saya, Hideyuki

    2014-01-01

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 high / Fbw7 high / c-Myc low and proliferative cancer stem-like cells with CD44v8-10 high / Fbw7 low / c-Myc high

  10. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Go J., E-mail: medical21go@yahoo.co.jp; Saya, Hideyuki

    2014-01-10

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup high}/ c-Myc {sup low} and proliferative cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup low}/ c-Myc {sup high}.

  11. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Srisuttee, Ratakorn [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Jhun, Byung Hak [Department of Applied Nanoscience, Pusan National University, Busan 609-735 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  12. The effect of microinjection of dimethyl sulfoxide into the rostral ventromedial medulla on swim stress-induced analgesia

    Directory of Open Access Journals (Sweden)

    S. Nazemi

    2018-02-01

    Full Text Available Background: Dimethyl sulfoxide (DMSO is an important solvent for compounds that used in pain research. Rostral ventromedial medulla (RVM plays an important role in modulating nociception and stress-induced analgesia (SIA. Objective: The aim of this study was to investigate the effect of DMSO administration into the RVM on SIA by using formalin test. Methods: This experimental study was conducted on 27 Wistar male rats (200±30 gr were randomly assigned to control, stress and stress+DMSO groups. Animals were placed in a water reservoir (20±1°C for 3 minutes to induce forced swimming stress. Stereotaxic surgery was performed to microinjection of DMSO (0.5μl, 100% into RVM. The pain behavior score was evaluated by subcutaneous injection of formalin 2% in the dorsal plantar region of hid paw. Findings: The pain score of phase 1, interphase and phase 2 of formalin test in swim stress group decreased significantly in comparison to control group (P<0.001, P< 0.05, P<0.001 respectively. In addition, the pain score of three phase of formalin test after DMSO injection in swim stress group decreased significantly in comparison to control and stress group (P<0.001, P<0.05 respectively. Conclusion: Also microinjections of DMSO into the RVM potentiate the swim stress analgesia. According to the analgesic effects of dimethyl sulfoxide, as well as its ability to potentiate stressinduced analgesia, DMSO should be used with caution as a solvent in pain studies. Conclusion: Force swim stress induces analgesia in, and microinjections of DMSO into the RVM potentiate the swim stress analgesia. According to the analgesic effects of DMSO, as well as its ability to potentiate stress-induced analgesia, it should be used with caution as solvent in pain studies.

  13. Stress-induced oxytocin release and oxytocin cell number and size in prepubertal and adult male and female rats.

    Science.gov (United States)

    Minhas, Sumeet; Liu, Clarissa; Galdamez, Josselyn; So, Veronica M; Romeo, Russell D

    2016-08-01

    Studies indicate that adolescent exposure to stress is a potent environmental factor that contributes to psychological and physiological disorders, though the mechanisms that mediate these dysfunctions are not well understood. Periadolescent animals display greater stress-induced hypothalamic-pituitary-adrenal (HPA) axis responses than adults, which may contribute to these vulnerabilities. In addition to the HPA axis, the hypothalamo-neurohypophyseal tract (HNT) is also activated in response to stress. In adults, stress activates this system resulting in secretion of oxytocin from neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. However, it is currently unknown whether a similar or different response occurs in prepubertal animals. Given the influence of these hormones on a variety of emotional behaviors and physiological systems known to change as an animal transitions into adulthood, we investigated stress-induced HPA and HNT hormonal responses before and after stress, as well as the number and size of oxytocin-containing cells in the SON and PVN of prepubertal (30d) and adult (70d) male and female rats. Though we found the well-established protracted adrenocorticotropic hormone and corticosterone response in prepubertal males and females, only adult males and prepubertal females showed a significant stress-induced increase in plasma oxytocin levels. Moreover, though we found no pubertal changes in the number of oxytocin cells, we did find a pubertal-related increase in oxytocin somal size in both the SON and PVN of males and females. Taken together, these data indicate that neuroendocrine systems can show different patterns of stress reactivity before and after adolescent development and that these responses can be further modified by sex. Given the impact of these hormones on a variety of systems, it will be imperative to further explore these changes in hormonal stress reactivity and their role in adolescent health. Copyright © 2016 Elsevier

  14. ADRA2B deletion variant selectively predicts stress-induced enhancement of long-term memory in females.

    Science.gov (United States)

    Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Lyle, Sarah M; Peters, David M; Brown, Callie M; Cadle, Chelsea E; Scharf, Amanda R; Dailey, Alison M; Wolters, Nicholas E; Talbot, Jeffery N; Rorabaugh, Boyd R

    2014-10-01

    Clarifying the mechanisms that underlie stress-induced alterations of learning and memory may lend important insight into susceptibility factors governing the development of stress-related psychological disorders, such as post-traumatic stress disorder (PTSD). Previous work has shown that carriers of the ADRA2B Glu(301)-Glu(303) deletion variant exhibit enhanced emotional memory, greater amygdala responses to emotional stimuli and greater intrusiveness of traumatic memories. We speculated that carriers of this deletion variant might also be more vulnerable to stress-induced enhancements of long-term memory, which would implicate the variant as a possible susceptibility factor for traumatic memory formation. One hundred and twenty participants (72 males, 48 females) submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they studied a list of 42 words varying in emotional valence and arousal and then completed an immediate free recall test. Twenty-four hours later, participants' memory for the word list was examined via free recall and recognition assessments. Stressed participants exhibiting greater heart rate responses to the stressor had enhanced recall on the 24-h assessment. Importantly, this enhancement was independent of the emotional nature of the learned information. In contrast to previous work, we did not observe a general enhancement of memory for emotional information in ADRA2B deletion carriers. However, stressed female ADRA2B deletion carriers, particularly those exhibiting greater heart rate responses to the stressor, did demonstrate greater recognition memory than all other groups. Collectively, these findings implicate autonomic mechanisms in the pre-learning stress-induced enhancement of long-term memory and suggest that the ADRA2B deletion variant may selectively predict stress effects on memory in females. Such findings lend important insight into the physiological mechanisms underlying stress

  15. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.

    Science.gov (United States)

    Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi

    2013-06-01

    Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Lulu Fan

    Full Text Available BACKGROUND: Endoplasmic reticulum stress (ER stress is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone, is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress-induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the effect of the endoplasmic reticulum (ER stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153 in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Pae reverses ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.

  17. Repeated Short-term (2h×14d) Emotional Stress Induces Lasting Depression-like Behavior in Mice.

    Science.gov (United States)

    Kim, Kyoung-Shim; Kwon, Hye-Joo; Baek, In-Sun; Han, Pyung-Lim

    2012-03-01

    Chronic behavioral stress is a risk factor for depression. To understand chronic stress effects and the mechanism underlying stress-induced emotional changes, various animals model have been developed. We recently reported that mice treated with restraints for 2 h daily for 14 consecutive days (2h-14d or 2h×14d) show lasting depression-like behavior. Restraint provokes emotional stress in the body, but the nature of stress induced by restraints is presumably more complex than emotional stress. So a question remains unsolved whether a similar procedure with "emotional" stress is sufficient to cause depression-like behavior. To address this, we examined whether "emotional" constraints in mice treated for 2h×14d by enforcing them to individually stand on a small stepping platform placed in a water bucket with a quarter full of water, and the stress evoked by this procedure was termed "water-bucket stress". The water-bucket stress activated the hypothalamus-pituitary-adrenal gland (HPA) system in a manner similar to restraint as evidenced by elevation of serum glucocorticoids. After the 2h×14d water-bucket stress, mice showed behavioral changes that were attributed to depression-like behavior, which was stably detected >3 weeks after last water-bucket stress endorsement. Administration of the anti-depressant, imipramine, for 20 days from time after the last emotional constraint completely reversed the stress-induced depression-like behavior. These results suggest that emotional stress evokes for 2h×14d in mice stably induces depression-like behavior in mice, as does the 2h×14d restraint.

  18. Coronary vascular age: An alternate means for predicting stress-induced myocardial ischemia in patients with suspected coronary artery disease.

    Science.gov (United States)

    Nappi, Carmela; Gaudieri, Valeria; Acampa, Wanda; Arumugam, Parthiban; Assante, Roberta; Zampella, Emilia; Mannarino, Teresa; Mainolfi, Ciro Gabriele; Imbriaco, Massimo; Petretta, Mario; Cuocolo, Alberto

    2018-01-22

    Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year's scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD). A total of 717 subjects referred to CAC scoring and 82 Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1). Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients. In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

  19. Ghrelin-reactive immunoglobulins and anxiety, depression and stress-induced cortisol response in adolescents. The TRAILS study.

    Science.gov (United States)

    François, Marie; Schaefer, Johanna M; Bole-Feysot, Christine; Déchelotte, Pierre; Verhulst, Frank C; Fetissov, Sergueï O

    2015-06-03

    Ghrelin, a hunger hormone, has been implicated in the regulation of stress-response, anxiety and depression. Ghrelin-reactive immunoglobulins (Ig) were recently identified in healthy and obese humans showing abilities to increase ghrelin's stability and orexigenic effects. Here we studied if ghrelin-reactive Ig are associated with anxiety and depression and with the stress-induced cortisol response in a general population of adolescents. Furthermore, to test the possible infectious origin of ghrelin-reactive Ig, their levels were compared with serum IgG against common viruses. We measured ghrelin-reactive IgM, IgG and IgA in serum samples of 1199 adolescents from the Dutch TRAILS study and tested their associations with 1) anxiety and depression symptoms assessed with the Youth Self-Report, 2) stress-induced salivary cortisol levels and 3) IgG against human herpesvirus 1, 2, 4 and 6 and Influenza A and B viruses. Ghrelin-reactive IgM and IgG correlated positively with levels of antibodies against Influenza A virus. Ghrelin-reactive IgM correlated negatively with antibodies against Influenza B virus. Ghrelin-reactive IgM correlated positively with anxiety scores in girls and ghrelin-reactive IgG correlated with stress-induced cortisol secretion, but these associations were weak and not significant after correction for multiple testing. These data indicate that production of ghrelin-reactive autoantibodies could be influenced by viral infections. Serum levels of ghrelin-reactive autoantibodies probably do not play a role in regulating anxiety, depression and the stress-response in adolescents from the general population. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Stress-induced formation mechanism of stacking fault tetrahedra in nano-cutting of single crystal copper

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Quanlong [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001 (China); Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001 (China); Bai, Qingshun [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001 (China); Chen, Jiaxuan, E-mail: wangquanlong0@hit.edu.cn [Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001 (China); Guo, Yongbo [Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001 (China); Xie, Wenkun [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001 (China); Center for Precision Engineering, Harbin Institute of Technology, Harbin 150001 (China)

    2015-11-15

    Graphical abstract: In this paper, molecular dynamics simulation is performed to study the distribution of dislocation defects and local atomic crystal structure of single crystal copper. The stress distribution is investigated which is calculated by virial stress and analyzed by static pressure. The results are shown in (a)–(d). It is indicated that the compressive stress mainly spreads over the shear-slip zone, and the tensile stress is consisted in flank friction zone, shown in (a). The high tensile stress in subsurface is the source of stress, shown in (b). By the driven action of the stress source, the initial stair-rod dislocation nucleates. Then the dislocation climbs along four {1 1 1} planes under the stress driven action, shown in (d). Finally, the SFT is formed by the interaction of the compressive stress and the tensile stress which come from the shear-slip zone and friction zone, respectively. Besides, stair-rod dislocation, stacking faults and dislocation loop are also nucleated in the subsurface, shown in (c). Dislocation distribution, local atomic crystal structure state and stress-induced formation process of SFT by atomic. - Highlights: • A novel defect structure “stress-induced stacking fault tetrahedra” is revealed. • Atomic structural evolution and stress state distribution of the SFT are studied. • The stress-induced formation mechanism of the SFT is proposed. - Abstract: Stacking fault tetrahedra commonly existed in subsurface of deformed face center cubic metals, has great influence on machining precision and surface roughness in nano-cutting. Here we report, a stacking fault tetrahedra is formed in subsurface of workpiece during nano-cutting. The variation of cutting force and subsurface defects distribution are studied by using molecular dynamics simulation. The stress distribution is investigated which is calculated by virial stress and analyzed by static compression. The result shows that the cutting force has a rapidly

  1. Stress-induced formation mechanism of stacking fault tetrahedra in nano-cutting of single crystal copper

    International Nuclear Information System (INIS)

    Wang, Quanlong; Bai, Qingshun; Chen, Jiaxuan; Guo, Yongbo; Xie, Wenkun

    2015-01-01

    Graphical abstract: In this paper, molecular dynamics simulation is performed to study the distribution of dislocation defects and local atomic crystal structure of single crystal copper. The stress distribution is investigated which is calculated by virial stress and analyzed by static pressure. The results are shown in (a)–(d). It is indicated that the compressive stress mainly spreads over the shear-slip zone, and the tensile stress is consisted in flank friction zone, shown in (a). The high tensile stress in subsurface is the source of stress, shown in (b). By the driven action of the stress source, the initial stair-rod dislocation nucleates. Then the dislocation climbs along four {1 1 1} planes under the stress driven action, shown in (d). Finally, the SFT is formed by the interaction of the compressive stress and the tensile stress which come from the shear-slip zone and friction zone, respectively. Besides, stair-rod dislocation, stacking faults and dislocation loop are also nucleated in the subsurface, shown in (c). Dislocation distribution, local atomic crystal structure state and stress-induced formation process of SFT by atomic. - Highlights: • A novel defect structure “stress-induced stacking fault tetrahedra” is revealed. • Atomic structural evolution and stress state distribution of the SFT are studied. • The stress-induced formation mechanism of the SFT is proposed. - Abstract: Stacking fault tetrahedra commonly existed in subsurface of deformed face center cubic metals, has great influence on machining precision and surface roughness in nano-cutting. Here we report, a stacking fault tetrahedra is formed in subsurface of workpiece during nano-cutting. The variation of cutting force and subsurface defects distribution are studied by using molecular dynamics simulation. The stress distribution is investigated which is calculated by virial stress and analyzed by static compression. The result shows that the cutting force has a rapidly

  2. A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qian; Ma, Ruonan; Tian, Ying [Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Liang, Yongdong; Feng, Hongqing [College of Engineering, Peking University, Beijing 100871 (China); Zhang, Jue; Fang, Jing [Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); College of Engineering, Peking University, Beijing 100871 (China)

    2013-05-20

    Ar/O{sub 2} (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

  3. A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

    International Nuclear Information System (INIS)

    Zhang, Qian; Ma, Ruonan; Tian, Ying; Liang, Yongdong; Feng, Hongqing; Zhang, Jue; Fang, Jing

    2013-01-01

    Ar/O 2 (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

  4. Serum Glutamic-Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) Levels in Children and Adolescents with Intellectual Disabilities

    Science.gov (United States)

    Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

    2010-01-01

    The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or…

  5. Growth- and Stress-Induced PASTA Kinase Phosphorylation in Enterococcus faecalis.

    Science.gov (United States)

    Labbe, Benjamin D; Kristich, Christopher J

    2017-11-01

    Transmembrane Ser/Thr kinases containing extracellular PASTA domains are ubiquitous among Actinobacteria and Firmicutes Such PASTA kinases regulate critical processes, including antibiotic resistance, cell division, toxin production, and virulence, and are essential for viability in certain organisms. Based on in vitro studies with purified extracellular and intracellular fragments of PASTA kinases, a model for signaling has been proposed, in which the extracellular PASTA domains bind currently undefined ligands (typically thought to be peptidoglycan, or fragments thereof) to drive kinase dimerization, which leads to enhanced kinase autophosphorylation and enhanced phosphorylation of substrates. However, this model has not been rigorously tested in vivo Enterococcus faecalis is a Gram-positive intestinal commensal and major antibiotic-resistant opportunistic pathogen. In E. faecalis , the PASTA kinase IreK drives intrinsic resistance to cell wall-active antimicrobials, suggesting that such antimicrobials may trigger IreK signaling. Here we show that IreK responds to cell wall stress in vivo by enhancing its phosphorylation and that of a downstream substrate. This response requires both the extracellular PASTA domains and specific phosphorylatable residues in the kinase domain. Thus, our results provide in vivo evidence, with an intact full-length PASTA kinase in its native physiological environment, that supports the prevailing model of PASTA kinase signaling. In addition, we show that IreK responds to a signal associated with growth and/or cell division, in the absence of cell wall-active antimicrobials. Surprisingly, the ability of IreK to respond to growth and/or division does not require the extracellular PASTA domains, suggesting that IreK monitors multiple parameters for sensory input in vivo IMPORTANCE Transmembrane Ser/Thr kinases containing extracellular PASTA domains are ubiquitous among Actinobacteria and Firmicutes and regulate critical processes. The

  6. Delineation of glutamate pathways and secretory responses in pancreatic islets with ß-cell-specific abrogation of the glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Vetterli, Laurene; Carobbio, Stefania; Pournourmohammadi, Shirin

    2012-01-01

    isolated from βGlud1(-/-) mice exhibited half of the response measured in control islets. The amplifying pathway, tested at stimulatory glucose concentrations in the presence of KCl and diazoxide, was markedly inhibited in βGlud1(-/-) islets. On glucose stimulation, net synthesis of glutamate from α......-ketoglutarate was impaired in GDH-deficient islets. Accordingly, glucose-induced elevation of glutamate levels observed in control islets was absent in βGlud1(-/-) islets. Parallel biochemical pathways, namely alanine and aspartate aminotransferases, could not compensate for the lack of GDH. However, the secretory response...... to glucose was fully restored by the provision of cellular glutamate when βGlud1(-/-) islets were exposed to dimethyl glutamate. This shows that permissive levels of glutamate are required for the full development of glucose-stimulated insulin secretion and that GDH plays an indispensable role...

  7. The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

    Science.gov (United States)

    Rojas, Donald C.

    2014-01-01

    Glutamate is the major excitatory neurotransmitter in the brain and may be a key neurotransmitter involved in autism. Literature pertaining to glutamate and autism or related disorders (e.g., Fragile X syndrome) is reviewed in this article. Interest in glutamatergic dysfunction in autism is high due to increasing convergent evidence implicating the system in the disorder from peripheral biomarkers, neuroimaging, protein expression, genetics and animal models. Currently, there are no pharmaceutical interventions approved for autism that address glutamate deficits in the disorder. New treatments related to glutamatergic neurotransmission, however, are emerging. In addition, older glutamate-modulating medications with approved indications for use in other disorders are being investigated for re-tasking as treatments for autism. This review presents evidence in support of glutamate abnormalities in autism and the potential for translation into new treatments for the disorder. PMID:24752754

  8. Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

    Science.gov (United States)

    Cheng, Yuyan; Pardo, Marta; de Souza Armini, Rubia; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S.; Beurel, Eleonore

    2016-01-01

    Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6 to 12 hr after stress. A 24 hr prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1 to 3 hr, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory

  9. Glutamate-induced glutamate release: A proposed mechanism for calcium bursting in astrocytes

    Science.gov (United States)

    Larter, Raima; Craig, Melissa Glendening

    2005-12-01

    Here we present a new model for the generation of complex calcium-bursting patterns in astrocytes, a type of brain cell recently implicated in a variety of neural functions including memory formation. The model involves two positive feedback processes, in which the key feedback species are calcium ion and glutamate. The latter is the most abundant excitatory neurotransmitter in the brain and has been shown to be involved in bidirectional communication between astrocytes and nearby neurons. The glutamate feedback process considered here is shown to be critical for the generation of complex bursting oscillations in the astrocytes and to, perhaps, code for information which may be passed from neuron to neuron via the astrocyte. These processes may be involved in memory storage and formation as well as in mechanisms which lead to dynamical diseases such as epilepsy.

  10. Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: A role for the IAPs

    International Nuclear Information System (INIS)

    Cheung, Herman H.; Lynn Kelly, N.; Liston, Peter; Korneluk, Robert G.

    2006-01-01

    Dysregulation of apoptosis is involved in a wide spectrum of disease ranging from proliferative to degenerative disorders. An emerging area of study in apoptosis is the critical contribution of the endoplasmic reticulum (ER) in both mitochondrial and ER specific apoptosis pathways. Here we show that brefeldin A and tunicamycin-mediated ER stress lead to caspase-dependent apoptosis involving caspase-2. Confocal microscopy and subcellular fractionation indicate that caspase-2 is localized to the ER, and following ER stress, the processing of caspase-2 and -9 is an early event preceding the activation of caspase-3 and -7 and the cleavage of the caspase substrate poly(ADP-ribose) polymerase (PARP). Inhibition and silencing of either caspase-2 or caspase-9 suppress ER stress-induced apoptosis, as demonstrated by annexin V binding. Similarly, transduction with an adenovirus encoding either Inhibitors of Apoptosis (IAP) protein HIAP1/c-IAP2 or HIAP2/c-IAP1 also suppresses ER stress-induced apoptosis. However, among HIAP1, HIAP2 and XIAP, only HIAP2 binds and inhibits caspase-2. Our results thus indicate a novel mechanism by which HIAP2 can regulate ER-initiated apoptosis by modulating the activity of caspase-2

  11. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway.

    Science.gov (United States)

    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G; Mungenast, Alison E; Deisseroth, Karl; Tsai, Li-Huei

    2015-06-09

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.

  12. Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

    Science.gov (United States)

    Hultman, Rainbo; Mague, Stephen D; Li, Qiang; Katz, Brittany M; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D; Dzirasa, Kafui

    2016-07-20

    Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

    Science.gov (United States)

    Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

    2017-08-01

    Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Science.gov (United States)

    Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior. PMID:26075223

  15. A novel kerf-free wafering process combining stress-induced spalling and low energy hydrogen implantation

    Energy Technology Data Exchange (ETDEWEB)

    Pingault, Timothee; Pokam-Kuisseu, Pauline Sylvia; Ntsoenzok, Esidor [CEMTHI - CNRS, Site Cyclotron, 3 A rue de la Ferollerie, 45071 Orleans (France); Blondeau, Jean-Philippe [CEMTHI - CNRS, Site Cyclotron, 3 A rue de la Ferollerie, 45071 Orleans (France); Universite d' Orleans, Chateau de la Source, 45100 Orleans (France); Ulyashin, Alexander [SINTEF, Forskningsveien 1, 0314 Oslo (Norway); Labrim, Hicham; Belhorma, Bouchra [CNESTEN, B.P. 1382 R.P., 10001 Rabat (Morocco)

    2016-12-15

    In this work, we studied the potential use of low-energy hydrogen implantation as a guide for the stress-induced cleavage. Low-energy, high fluence hydrogen implantation in silicon leads, in the right stiffening conditions, to the detachment of a thin layer, around a few hundreds nm thick, of monocrystalline silicon. We implanted monocrystalline silicon wafers with low-energy hydrogen, and then glued them on a cheap metal layer. Upon cooling down, the stress induced by the stressor layers (hardened glue and metal) leads to the detachment of a thin silicon layer, which thickness is determined by the implantation energy. We were then able to clearly demonstrate that, as expected, hydrogen oversaturation layer is very efficient to guide the stress. Using such process, thin silicon layers of around 710 nm-thick were successfully detached from low-energy implanted silicon wafers. Such layers can be used for the growth of very good quality monocrystalline silicon of around 50 μm-thick or less. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation.

    Science.gov (United States)

    Han, Xiaojuan; Tai, Haoran; Wang, Xiaobo; Wang, Zhe; Zhou, Jiao; Wei, Xiawei; Ding, Yi; Gong, Hui; Mo, Chunfen; Zhang, Jie; Qin, Jianqiong; Ma, Yuanji; Huang, Ning; Xiang, Rong; Xiao, Hengyi

    2016-06-01

    AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress-induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide-induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP-RFP-LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD(+) levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD(+) synthesis. In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence by improving autophagic flux and NAD(+) homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD(+) homeostasis, and it is also valuable in the development of innovative strategies to combat aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  17. Chewing prevents stress-induced hippocampal LTD formation and anxiety-related behaviors: a possible role of the dopaminergic system.

    Science.gov (United States)

    Ono, Yumie; Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  18. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Directory of Open Access Journals (Sweden)

    Yumie Ono

    2015-01-01

    Full Text Available The present study examined the effects of chewing on stress-induced long-term depression (LTD and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  19. Critical features of acute stress-induced cross-sensitization identified through the hypothalamic-pituitary-adrenal axis output.

    Science.gov (United States)

    Belda, Xavier; Nadal, Roser; Armario, Antonio

    2016-08-11

    Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors.

  20. From the Hayflick mosaic to the mosaics of ageing. Role of stress-induced premature senescence in human ageing.

    Science.gov (United States)

    Toussaint, Olivier; Remacle, Jose; Dierick, Jean-François; Pascal, Thierry; Frippiat, Christophe; Zdanov, Stéphanie; Magalhaes, Joao Pedro; Royer, Véronique; Chainiaux, Florence

    2002-11-01

    The Hayflick limit-senescence of proliferative cell types-is a fundamental feature of proliferative cells in vitro. Various human proliferative cell types exposed in vitro to many types of subcytotoxic stresses undergo stress-induced premature senescence (SIPS) (also called stress-induced premature senescence-like phenotype, according to the definition of senescence). The known mechanisms of appearance the main features of SIPS are reviewed: senescent-like morphology, growth arrest, senescence-related changes in gene expression, telomere shortening. Long before telomere-shortening induces senescence, other factors such as culture conditions or lack of 'feeder cells' can trigger either SIPS or prolonged reversible G(0) phase of the cell cycle. In vivo, 'proliferative' cell types of aged individuals are likely to compose a mosaic made of cells irreversibly growth arrested or not. The higher level of stress to which these cells have been exposed throughout their life span, the higher proportion of the cells of this mosaic will be in SIPS rather than in telomere-shortening dependent senescence. All cell types undergoing SIPS in vivo, most notably the ones in stressful conditions, are likely to participate in the tissular changes observed along ageing. For instance, human diploid fibroblasts (HDFs) exposed in vivo and in vitro to pro-inflammatory cytokines display biomarkers of senescence and might participate in the degradation of the extracellular matrix observed in ageing.

  1. The Effect of Exercise on Learning and Spatial Memory Following Stress-Induced Sleep Deprivation (Sleep REM in Rats

    Directory of Open Access Journals (Sweden)

    Darkhah

    2016-04-01

    Full Text Available Background Stress induced by sleep deprivation can cause degradation of learning in the acquisition phase, and low-intensity exercise can prevent the negative effects of stress. Objectives The aim of this study was to investigate the moderating role of aerobic exercise on spatial memory and learning following stress-induced insomnia (sleep REM in animal models. Materials and Methods This experimental study was conducted on adult male Wistar rats that were randomly divided into two groups. Both groups were exposed to sleep deprivation induced stress, following which the experimental group was exposed to exercise training (experimental, n = 8; control, n = 8. The stress intervention was undertaken through 24 hours of sleep deprivation using a modified sleep deprivation platform (MMD. The exercise protocol included mild aerobic exercise on a treadmill (30 minutes a day, seven days, and Morris Water Maze (MWM protocols were applied to assess spatial memory and learning. Data were analyzed by an independent t-test and dependent t-test. Results The results showed that, after seven days of aerobic exercise on a treadmill, the experimental group showed better performance escape latency (P < 0.05 and distance traveled (P < 0.05 than the control group in the MWM, while there was no difference between these two groups in the pre-test. Conclusions The role of exercise is greater in the retention than the acquisition phase for recalling past experiences.

  2. Nocturnal insomnia symptoms and stress-induced cognitive intrusions in risk for depression: A 2-year prospective study.

    Science.gov (United States)

    Kalmbach, David A; Pillai, Vivek; Drake, Christopher L

    2018-01-01

    Nearly half of US adults endorse insomnia symptoms. Sleep problems increase risk for depression during stress, but the mechanisms are unclear. During high stress, individuals having difficulty falling or staying asleep may be vulnerable to cognitive intrusions after stressful events, given that the inability to sleep creates a period of unstructured and socially isolated time in bed. We investigated the unique and combined effects of insomnia symptoms and stress-induced cognitive intrusions on risk for incident depression. 1126 non-depressed US adults with no history of DSM-5 insomnia disorder completed 3 annual web-based surveys on sleep, stress, and depression. We examined whether nocturnal insomnia symptoms and stress-induced cognitive intrusions predicted depression 1y and 2y later. Finally, we compared depression-risk across four groups: non-perseverators with good sleep, non-perseverators with insomnia symptoms, perseverators with good sleep, and perseverators with insomnia symptoms. Insomnia symptoms (β = .10-.13, p good sleeping non-perseverators had the lowest rates (3.3%, Relative Risk = 3.94). Perseverators with sleep latency >30 m reported greater depression than good sleeping perseverators (t = 2.09, p stress creates a depressogenic mindset, and nocturnal wakefulness may augment the effects of cognitive arousal on depression development. Poor sleepers may be especially vulnerable to cognitive intrusions when having difficulty initiating sleep. As treatable behaviors, nighttime wakefulness and cognitive arousal may be targeted to reduce risk for depression in poor sleepers.

  3. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

    Science.gov (United States)

    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G.; Mungenast, Alison E.; Deisseroth, Karl; Tsai, Li-Huei

    2015-01-01

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation. PMID:25995364

  4. The γ-ε martensitic transformation: a model for stress induced variant and its interaction with grain boundary

    International Nuclear Information System (INIS)

    Guenin, G.

    1995-01-01

    The γ (f.c.c.) to ε (h.c.p.) martensitic transformation occurs through the Shockley a/6 left angle 211 right angle faulting every second {111} plane of the f.c.c. structure. A stress induced thin single variant corresponds to a single a/6 left angle 211 right angle faulting vector and leads to a large homogeneous shear (0.35) in amplitude. The tip of such a plate is composed of a set of identical Shockley partial dislocations with large mutual interactions. This work is a presentation of a model which describes the martensite morphology of stress induced ε martensite in shape memory Fe-Mn-Si based alloys. The model includes the formation mechanism of the plate (Seeger's like) and its growth inside a limited grain. The mutual interaction of Shockley dislocations and their interaction with the grain boundary is semi quantitatively described; it leads to a lenticular shape of ε martensite thin plates. The model is able to explain the behaviour of this kind of alloys concerning the superelastic effect and the shape memory. (orig.)

  5. Effect of Applied Stress and Temperature on Residual Stresses Induced by Peening Surface Treatments in Alloy 600

    Science.gov (United States)

    Telang, A.; Gnäupel-Herold, T.; Gill, A.; Vasudevan, V. K.

    2018-04-01

    In this study, the effects of applied tensile stress and temperature on laser shock peening (LSP) and cavitation shotless peening (CSP)-induced compressive residual stresses were investigated using neutron and x-ray diffraction. Residual stresses on the surface, measured in situ, were lower than the applied stress in LSP- and CSP-treated Alloy 600 samples (2 mm thick). The residual stress averaged over the volume was similar to the applied stress. Compressive residual stresses on the surface and balancing tensile stresses in the interior relax differently due to hardening induced by LSP. Ex situ residual stress measurements, using XRD, show that residual stresses relaxed as the applied stress exceeded the yield strength of the LSP- and CSP-treated Alloy 600. Compressive residual stresses induced by CSP and LSP decreased by 15-25% in magnitude, respectively, on exposure to 250-450 °C for more than 500 h with 10-11% of relaxation occurring in the first few hours. Further, 80% of the compressive residual stresses induced by LSP and CSP treatments in Alloy 600 were retained even after long-term aging at 350 °C for 2400 h.

  6. Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation.

    Science.gov (United States)

    Gaab, Jens; Jiménez, Julia; Voneschen, Livia; Oschwald, Daniel; Meyer, Andrea H; Nater, Urs M; Krummenacher, Peter

    2016-01-01

    Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation. © 2017 S. Karger AG, Basel.

  7. Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults.

    Science.gov (United States)

    Shin, Min Jea; Kim, Dae Won; Jo, Hyo Sang; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Kim, Ji An; Hwang, Jung Soon; Sohn, Eun Jeong; Jeong, Ji-Heon; Kim, Duk-Soo; Kwon, Hyeok Yil; Cho, Yong-Jun; Lee, Keunwook; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2016-08-01

    Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia. We showed that Tat-PRAS40 transduced into HT-22 cells, and significantly protected against cell death by reducing the levels of H2O2 and derived reactive species, and DNA fragmentation as well as via the regulation of Bcl-2, Bax, and caspase 3 expression levels in H2O2 treated cells. Also, we showed that transduced Tat-PARS40 protein markedly increased phosphorylated RRAS40 expression levels and 14-3-3σ complex via the Akt signaling pathway. In an animal ischemia model, Tat-PRAS40 effectively transduced into the hippocampus in animal brain and significantly protected against neuronal cell death in the CA1 region. We showed that Tat-PRAS40 protein effectively transduced into hippocampal neuronal cells and markedly protected against neuronal cell damage. Therefore, we suggest that Tat-PRAS40 protein may be used as a therapeutic protein for ischemia and oxidative stress-induced brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Effects of Red Wine Tannat on Oxidative Stress Induced by Glucose and Fructose in Erythrocytes in Vitro

    Science.gov (United States)

    Pazzini, Camila Eliza Fernandes; Colpo, Ana Ceolin; Poetini, Márcia Rósula; Pires, Cauê Ferreira; de Camargo, Vanessa Brum; Mendez, Andreas Sebastian Loureiro; Azevedo, Miriane Lucas; Soares, Júlio César Mendes; Folmer, Vanderlei

    2015-01-01

    The literature indicates that red wine presents in its composition several substances that are beneficial to health. This study has investigated the antioxidant effects of Tannat red wine on oxidative stress induced by glucose and fructose in erythrocytes in vitro, with the purpose to determine some of its majoritarian phenolic compounds and its antioxidant capacity. Erythrocytes were incubated using different concentrations of glucose and fructose in the presence or absence of wine. From these erythrocytes were determined the production of thiobarbituric acid reactive species (TBARS), glucose consumption, and osmotic fragility. Moreover, quantification of total phenolic, gallic acid, caffeic acid, epicatechin, resveratrol, and DPPH scavenging activity in wine were also assessed. Red wine showed high levels of polyphenols analyzed, as well as high antioxidant potential. Erythrocytes incubated with glucose and fructose had an increase in lipid peroxidation and this was prevented by the addition of wine. The wine increased glucose uptake into erythrocytes and was able to decrease the osmotic fragility of erythrocytes incubated with fructose. Altogether, these results suggest that wine leads to a reduction of the oxidative stress induced by high concentrations of glucose and fructose. PMID:26078708

  9. Glutamate and GABA in appetite regulation

    Directory of Open Access Journals (Sweden)

    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  10. Baseline and stress-induced levels of corticosterone in male and female Afrotropical and European temperate stonechats during breeding.

    Science.gov (United States)

    Apfelbeck, Beate; Helm, Barbara; Illera, Juan Carlos; Mortega, Kim G; Smiddy, Patrick; Evans, Neil P

    2017-05-22

    Latitudinal variation in avian life histories falls along a slow-fast pace of life continuum: tropical species produce small clutches, but have a high survival probability, while in temperate species the opposite pattern is found. This study investigated whether differential investment into reproduction and survival of tropical and temperate species is paralleled by differences in the secretion of the vertebrate hormone corticosterone (CORT). Depending on circulating concentrations, CORT can both act as a metabolic (low to medium levels) and a stress hormone (high levels) and, thereby, influence reproductive decisions. Baseline and stress-induced CORT was measured across sequential stages of the breeding season in males and females of closely related taxa of stonechats (Saxicola spp) from a wide distribution area. We compared stonechats from 13 sites, representing Canary Islands, European temperate and East African tropical areas. Stonechats are highly seasonal breeders at all these sites, but vary between tropical and temperate regions with regard to reproductive investment and presumably also survival. In accordance with life-history theory, during parental stages, post-capture (baseline) CORT was overall lower in tropical than in temperate stonechats. However, during mating stages, tropical males had elevated post-capture (baseline) CORT concentrations, which did not differ from those of temperate males. Female and male mates of a pair showed correlated levels of post-capture CORT when sampled after simulated territorial intrusions. In contrast to the hypothesis that species with low reproduction and high annual survival should be more risk-sensitive, tropical stonechats had lower stress-induced CORT concentrations than temperate stonechats. We also found relatively high post-capture (baseline) and stress-induced CORT concentrations, in slow-paced Canary Islands stonechats. Our data support and refine the view that baseline CORT facilitates energetically

  11. Posttranslational Modification Biology of Glutamate Receptors and Drug Addiction

    Directory of Open Access Journals (Sweden)

    Li-Min eMao

    2011-03-01

    Full Text Available Posttranslational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues on their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling and protein-protein interactions, subcellular redistribution (trafficking, endocytosis, synaptic delivery and clustering, and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamines. Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

  12. Food Application of Newly Developed Handy-type Glutamate Sensor.

    Science.gov (United States)

    Mukai, Yuuka; Oikawa, Tsutomu

    2016-01-01

    Tests on physiological functions of umami have been actively conducted and a need recognized for a high-performance quantification device that is simple and cost-effective, and whose use is not limited to a particular location or user. To address this need, Ajinomoto Co. and Tanita Corp. have jointly been researching and developing a simple device for glutamate measurement. The device uses L-glutamate oxidase immobilized on a hydrogen peroxide electrode. L-glutamate in the sample is converted to α-ketoglutaric acid, which produces hydrogen peroxide. Subsequently, the electrical current from the electrochemical reaction of hydrogen peroxide is measured to determine the L-glutamate concentration. In order to evaluate its basic performance, we used this device to measure the concentration of L-glutamate standard solutions. In a concentration range of 0-1.0%, the difference from the theoretical value was minimal. The coefficient of variation (CV) value of 3 measurements was 4% or less. This shows that the device has a reasonable level of precision and accuracy. The device was also used in trial measurements of L-glutamate concentrations in food. There was a good correlation between the results obtained using the developed device and those obtained with an amino acid analyzer; the correlation coefficient was R=0.997 (n=24). In this review, we demonstrate the use of our device to measure the glutamate concentration in miso soup served daily at a home for elderly people, and other foods and ingredients.

  13. Role of aminotransferases in glutamate metabolism of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger, James J. [University of Wisconsin-Madison, Department of Biochemistry (United States); Lewis, Ian A. [Princeton University, Lewis-Sigler Institute for Integrative Genomics (United States); Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, Department of Biochemistry (United States)

    2011-04-15

    Human erythrocytes require a continual supply of glutamate to support glutathione synthesis, but are unable to transport this amino acid across their cell membrane. Consequently, erythrocytes rely on de novo glutamate biosynthesis from {alpha}-ketoglutarate and glutamine to maintain intracellular levels of glutamate. Erythrocytic glutamate biosynthesis is catalyzed by three enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamine aminohydrolase (GA). Although the presence of these enzymes in RBCs has been well documented, the relative contributions of each pathway have not been established. Understanding the relative contributions of each biosynthetic pathway is critical for designing effective therapies for sickle cell disease, hemolytic anemia, pulmonary hypertension, and other glutathione-related disorders. In this study, we use multidimensional {sup 1}H-{sup 13}C nuclear magnetic resonance (NMR) spectroscopy and multiple reaction mode mass spectrometry (MRM-MS) to measure the kinetics of de novo glutamate biosynthesis via AST, ALT, and GA in intact cells and RBC lysates. We show that up to 89% of the erythrocyte glutamate pool can be derived from ALT and that ALT-derived glutamate is subsequently used for glutathione synthesis.

  14. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

  15. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, Maarten

    2015-01-01

    In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate

  16. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  17. Oxidative stress induced by chlorine dioxide as an insecticidal factor to the Indian meal moth, Plodia interpunctella.

    Science.gov (United States)

    Kumar, Sunil; Park, Jiyeong; Kim, Eunseong; Na, Jahyun; Chun, Yong Shik; Kwon, Hyeok; Kim, Wook; Kim, Yonggyun

    2015-10-01

    A novel fumigant, chlorine dioxide (ClO2) is a commercial bleaching and disinfection agent. Recent study indicates its insecticidal activity. However, its mode of action to kill insects is yet to be understood. This study set up a hypothesis that an oxidative stress induced by ClO2 is a main factor to kill insects. The Indian meal moth, Plodia interpunctella, is a lepidopteran insect pest infesting various stored grains. Larvae of P. interpunctella were highly susceptible to ClO2 gas, which exhibited an acute toxicity. Physiological damages by ClO2 were observed in hemocytes. At high doses, the larvae of P. interpunctella suffered significant reduction of total hemocytes. At low doses, ClO2 impaired hemocyte behaviors. The cytotoxicity of ClO2 was further analyzed using two insect cell lines, where Sf9 cells were more susceptible to ClO2 than High Five cells. The cells treated with ClO2 produced reactive oxygen species (ROS). The produced ROS amounts increased with an increase of the treated ClO2 amount. However, the addition of an antioxidant, vitamin E, significantly attenuated the cytotoxicity of ClO2 in a dose-dependent manner. To support the oxidative stress induced by ClO2, two antioxidant genes (superoxide dismutase (SOD) and thioredoxin-peroxidase (Tpx)) were identified from P. interpunctella EST library using ortholog sequences of Bombyx mori. Both SOD and Tpx were expressed in larvae of P. interpunctella especially under oxidative stress induced by bacterial challenge. Exposure to ClO2 gas significantly induced the gene expression of both SOD and Tpx. RNA interference of SOD or Tpx using specific double stranded RNAs significantly enhanced the lethality of P. interpunctella to ClO2 gas treatment as well as to the bacterial challenge. These results suggest that ClO2 induces the production of insecticidal ROS, which results in a fatal oxidative stress in P. interpunctella. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis

    International Nuclear Information System (INIS)

    Bruchmann, Anja; Roller, Corinna; Walther, Tamara Vanessa; Schäfer, Georg; Lehmusvaara, Sara; Visakorpi, Tapio; Klocker, Helmut; Cato, Andrew C B; Maddalo, Danilo

    2013-01-01

    The Bag (Bcl-2 associated athanogene) family of proteins consists of 6 members sharing a common, single-copied Bag domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in the Bag family since it consists of 5 Bag domains covering the whole protein. Bag proteins like Bag1 and Bag3 have been implicated in tumor growth and survival but it is not known whether Bag5 also exhibits this function. Bag5 mRNA and protein expression levels were investigated in prostate cancer patient samples using real-time PCR and immunoblot analyses. In addition immunohistological studies were carried out to determine the expression of Bag5 in tissue arrays. Analysis of Bag5 gene expression was carried out using one-way ANOVA and Bonferroni’s Multiple Comparison test. The mean values of the Bag5 stained cells in the tissue array was analyzed by Mann-Whitney test. Functional studies of the role of Bag5 in prostate cancer cell lines was performed using overexpression and RNA interference analyses. Our results show that Bag5 is overexpressed in malignant prostate tissue compared to benign samples. In addition we could show that Bag5 levels are increased following endoplasmic reticulum (ER)-stress induction, and Bag5 relocates from the cytoplasm to the ER during this process. We also demonstrate that Bag5 interacts with the ER-resident chaperone GRP78/BiP and enhances its ATPase activity. Bag5 overexpression in 22Rv.1 prostate cancer cells inhibited ER-stress induced apoptosis in the unfolded protein response by suppressing PERK-eIF2-ATF4 activity while enhancing the IRE1-Xbp1 axis of this pathway. Cells expressing high levels of Bag5 showed reduced sensitivity to apoptosis induced by different agents while Bag5 downregulation resulted in increased stress-induced cell death. We have therefore shown that Bag5 is overexpressed in prostate cancer and plays a role in ER-stress induced apoptosis. Furthermore we have identified GRP78/BiP as a novel

  19. Selective attenuation of norepinephrine release and stress-induced heart rate increase by partial adenosine A1 agonism.

    Directory of Open Access Journals (Sweden)

    Lorenz Bott-Flügel

    Full Text Available The release of the neurotransmitter norepinephrine (NE is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR, NE release was induced by electrical stimulation under control conditions (S1, and with capadenoson 6 · 10(-8 M (30 µg/l, 6 · 10(-7 M (300 µg/l or 2-chloro-N(6-cyclopentyladenosine (CCPA 10(-6 M (S2. Under control conditions (S1, NE release was significantly higher in SHR hearts compared to Wistar (766+/-87 pmol/g vs. 173+/-18 pmol/g, p<0.01. Capadenoson led to a concentration-dependent decrease of the stimulation-induced NE release in SHR (S2/S1  =  0.90 ± 0.08 with capadenoson 6 · 10(-8 M, 0.54 ± 0.02 with 6 · 10(-7 M, but not in Wistar hearts (S2/S1  =  1.05 ± 0.12 with 6 · 10(-8 M, 1.03 ± 0.09 with 6 · 10(-7 M. CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [(35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/-2% A(1-receptor stimulation. These results suggest that partial adenosine A(1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release.

  20. Inhibition of the Mitochondrial Glutamate Carrier SLC25A22 in Astrocytes Leads to Intracellular Glutamate Accumulation

    Directory of Open Access Journals (Sweden)

    Emmanuelle Goubert

    2017-05-01

    Full Text Available The solute carrier family 25 (SLC25 drives the import of a large diversity of metabolites into mitochondria, a key cellular structure involved in many metabolic functions. Mutations of the mitochondrial glutamate carrier SLC25A22 (also named GC1 have been identified in early epileptic encephalopathy (EEE and migrating partial seizures in infancy (MPSI but the pathophysiological mechanism of GC1 deficiency is still unknown, hampered by the absence of an in vivo model. This carrier is mainly expressed in astrocytes and is the principal gate for glutamate entry into mitochondria. A sufficient supply of energy is essential for the proper function of the brain and mitochondria have a pivotal role in maintaining energy homeostasis. In this work, we wanted to study the consequences of GC1 absence in an in vitro model in order to understand if glutamate catabolism and/or mitochondrial function could be affected. First, short hairpin RNA (shRNA designed to specifically silence GC1 were validated in rat C6 glioma cells. Silencing GC1 in C6 resulted in a reduction of the GC1 mRNA combined with a decrease of the mitochondrial glutamate carrier activity. Then, primary astrocyte cultures were prepared and transfected with shRNA-GC1 or mismatch-RNA (mmRNA constructs using the Neon® Transfection System in order to target a high number of primary astrocytes, more than 64%. Silencing GC1 in primary astrocytes resulted in a reduced nicotinamide adenine dinucleotide (Phosphate (NAD(PH formation upon glutamate stimulation. We also observed that the mitochondrial respiratory chain (MRC was functional after glucose stimulation but not activated by glutamate, resulting in a lower level of cellular adenosine triphosphate (ATP in silenced astrocytes compared to control cells. Moreover, GC1 inactivation resulted in an intracellular glutamate accumulation. Our results show that mitochondrial glutamate transport via GC1 is important in sustaining glutamate homeostasis in

  1. Exercise-Induced Rhabdomyolysis and Stress-Induced Malignant Hyperthermia Events, Association with Malignant Hyperthermia Susceptibility, and RYR1 Gene Sequence Variations

    Directory of Open Access Journals (Sweden)

    Antonella Carsana

    2013-01-01

    Full Text Available Exertional rhabdomyolysis (ER and stress-induced malignant hyperthermia (MH events are syndromes that primarily afflict military recruits in basic training and athletes. Events similar to those occurring in ER and in stress-induced MH events are triggered after exposure to anesthetic agents in MH-susceptible (MHS patients. MH is an autosomal dominant hypermetabolic condition that occurs in genetically predisposed subjects during general anesthesia, induced by commonly used volatile anesthetics and/or the neuromuscular blocking agent succinylcholine. Triggering agents cause an altered intracellular calcium regulation. Mutations in RYR1 gene have been found in about 70% of MH families. The RYR1 gene encodes the skeletal muscle calcium release channel of the sarcoplasmic reticulum, commonly known as ryanodine receptor type 1 (RYR1. The present work reviews the documented cases of ER or of stress-induced MH events in which RYR1 sequence variations, associated or possibly associated to MHS status, have been identified.

  2. Metabolic control of vesicular glutamate transport and release.

    Science.gov (United States)

    Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

    2010-10-06

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. In vitro evidence for the brain glutamate efflux hypothesis

    DEFF Research Database (Denmark)

    Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby

    2012-01-01

    resistance values of 1014 ± 70 O cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids......The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L......-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial...

  4. Histochemical Studies of the Effects of Monosodium Glutamate on ...

    African Journals Online (AJOL)

    Uche

    Key words: Monosodium glutamate; histochemical effect; liver enzymes; hepatocytes; atrophic and degenerative changes;. Wistar rats. ... disease, Huntington‟s disease, and amyotrophic ... ascending grade of alcohol (ethanol), cleared in.

  5. Detection and quantitation of glutamate carboxypeptidase II in human blood

    Czech Academy of Sciences Publication Activity Database

    Knedlík, Tomáš; Navrátil, Václav; Vik, V.; Pacík, D.; Šácha, Pavel; Konvalinka, Jan

    2014-01-01

    Roč. 74, č. 7 (2014), s. 768-780 ISSN 0270-4137 R&D Projects: GA ČR GAP304/12/0847 Grant - others:OPPC(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : serum marker * glutamate carboxypeptidase II * plasma glutamate carboxypeptidase * prostate cancer * prostate -specific membrane antigen Subject RIV: CE - Biochemistry Impact factor: 3.565, year: 2014

  6. Immunochemical characterization of the brain glutamate binding protein

    International Nuclear Information System (INIS)

    Roy, S.

    1986-01-01

    A glutamate binding protein (GBP) was purified from bovine and rat brain to near homogeneity. Polyclonal antibodies were raised against this protein. An enzyme-linked-immunosorbent-assay was used to quantify and determine the specificity of the antibody response. The antibodies were shown to strongly react with bovine brain GBP and the analogous protein from rat brain. The antibodies did not show any crossreactivity with the glutamate metabolizing enzymes, glutamate dehydrogenase, glutamine synthetase and glutamyl transpeptidase, however it crossreacted moderately with glutamate decarboxylase. The antibodies were also used to define the possible physiologic activity of GBP in synaptic membranes. The antibodies were shown: (i) to inhibit the excitatory amino-acid stimulation of thiocyanate (SCN)flux, (ii) had no effect on transport of L-Glutamic acid across the synaptic membrane, and (iii) had no effect on the depolarization-induced release of L-glutamate. When the anti-GBP antibodies were used to localize and quantify the GBP distribution in various subcellular fractions and in brain tissue samples, it was found that the hippocampus had the highest immunoreactivity followed by the cerebral cortex, cerebellar cortex and caudate-putamen. The distribution of immunoreactivity in the subcellular fraction were as follows: synaptic membranes > crude mitochondrial fraction > homogenate > myelin. In conclusion these studies suggest that: (a) the rat brain GBP and the bovine brain GBP are immunologically homologous protein, (b) there are no structural similarities between the GBP and the glutamate metabolizing enzymes with the exception of glutamate decarboxylase and (c) the subcellular and regional distribution of the GBP immunoreactivity followed a similar pattern as observed for L-[ 3 H]-binding

  7. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    Science.gov (United States)

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-04

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  8. In Vivo Measurements of Glutamate, GABA, and NAAG in Schizophrenia

    OpenAIRE

    Rowland, Laura M.; Kontson, Kimberly; West, Jeffrey; Edden, Richard A.; Zhu, He; Wijtenburg, S. Andrea; Holcomb, Henry H.; Barker, Peter B.

    2012-01-01

    The major excitatory and inhibitory neurotransmitters, glutamate (Glu) and gamma-aminobutyric acid (GABA), respectively, are implicated in the pathophysiology of schizophrenia. N-acetyl-aspartyl-glutamate (NAAG), a neuropeptide that modulates the Glu system, may also be altered in schizophrenia. This study investigated GABA, Glu + glutamine (Glx), and NAAG levels in younger and older subjects with schizophrenia. Forty-one subjects, 21 with chronic schizophrenia and 20 healthy controls, partic...

  9. Effect of Si on the reversibility of stress-induced martensite in Fe-Mn-Si shape memory alloys

    Energy Technology Data Exchange (ETDEWEB)

    Stanford, N. [Centre for Material and Fibre Innovation, Deakin University, Geelong, Victoria 3217 (Australia); Dunne, D.P., E-mail: druce_dunne@uow.edu.au [Faculty of Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2010-12-15

    Fe-Mn-Si is a well-characterized ternary shape memory alloy. Research on this alloy has consistently shown that the addition of 5-6 wt.% Si is desirable to enhance the reversibility of stress-induced martensite vis-a-vis shape memory. This paper examines the effect of Si on the morphology and the crystallography of the martensite in the Fe-Mn-Si system. It is concluded that the addition of Si increases the c/a ratio of the martensite, reduces the transformation volume change and decreases the atomic spacing difference between the parallel close-packed directions in the austenite-martensite interface (habit) plane. It is proposed that, in addition to austenite strengthening, Si enhances reversibility by reducing the volume change and the interfacial atomic mismatch between the martensite and the austenite. Although shape memory is improved, transformation reversibility remains limited by the necessary misfit dislocations that accommodate the atomic spacing differences in the interface.

  10. Pharmacological Correction of Stress-Induced Gastric Ulceration by Novel Small-Molecule Agents with Antioxidant Profile

    Directory of Open Access Journals (Sweden)

    Konstantin V. Kudryavtsev

    2014-01-01

    Full Text Available This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

  11. On the relation between quasi-static and dynamic stress induced reversible structural relaxation of amorphous alloys

    International Nuclear Information System (INIS)

    Krueger, P.; Stucky, T.; Boewe, M.; Neuhaeuser, H.

    1993-01-01

    Quasi-static stress relaxation and dynamic internal friction measurements of stress induced reversible structural relaxation were performed on the amorphous alloy Fe 40 Ni 40 B 20 . The kinetics can be well described by a stretched exponential Kohlrausch-Williams-Watts quasi-static relaxation. The thermally activated part of the internal friction shows an Arrhenius temperature behaviour for a fixed vibration frequency and an inverse power frequency behaviour for a fixed temperature. The activation energies calculated from the Arrhenius equation and from the frequency shift method are significantly different. In order to explain this discrepancy the relation between the quasi-static and the dynamic descriptions of the reversible relaxation is reexamined. In particular it is shown that these two activation energies are connected by the Kohlrausch exponent of the quasi-static relaxation. (orig.)

  12. In Vitro Production of Fumonisins by Fusarium verticillioides under Oxidative Stress Induced by H2O2.

    Science.gov (United States)

    Ferrigo, Davide; Raiola, Alessandro; Bogialli, Sara; Bortolini, Claudio; Tapparo, Andrea; Causin, Roberto

    2015-05-20

    The effects of oxidative stress induced by H2O2 were tested in liquid cultures in the fumonisin-producing fungus Fusarium verticillioides. The quantitative analysis of fumonisins B1, B2, B3, and B4 was achieved by means of liquid chromatography coupled to high-resolution mass spectrometry. Two effects in F. verticillioides, consisting of different abilities to produce fumonisins in response to oxidative stress, were identified. Following H2O2 addition, two F. verticillioides strains produced significantly more fumonisin (>300%) while three other strains produced significantly less (fumonisin and either no or minimal changes in the strain that made less fumonisin. Our data indicate the important role of oxidative stress toward the modulation of the fumonisin biosynthesis and suggest the necessity to verify the presence of such divergent behavior in F. verticillioides populations under natural conditions.

  13. ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

    2009-11-30

    Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

  14. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

    Science.gov (United States)

    Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

    2014-02-01

    Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized. © 2014 International Life Sciences Institute.

  15. Chewing suppresses the stress-induced increase in the number of pERK-immunoreactive cells in the periaqueductal grey.

    Science.gov (United States)

    Yamada, Kentaro; Narimatsu, Yuri; Ono, Yumie; Sasaguri, Ken-Ichi; Onozuka, Minoru; Kawata, Toshitsugu; Yamamoto, Toshiharu

    2015-07-10

    We investigated the effects of chewing under immobilization stress on the periaqueductal gray (PAG) matter using phosphorylated extracellular signal-regulated kinase (pERK) as a marker of responding cells. Immobilization stress increased pERK-immunoreactive cells in the PAG. Among four subdivisions of the PAG, the increase of immunoreactive cells was remarkable in the dorsolateral and ventrolateral subdivisions. However, increase of pERK-immunoreactive cells by the immobilization stress was not so evident in the dorsomedial and lateral subdivisions. The chewing under immobilization stress prevented the stress-induced increase of pERK-immunoreactive cells in the dorsolateral and ventrolateral subdivisions with statistical significances (p<0.05). Again, chewing effects on pERK-immunoreactive cells were not visible in the dorsomedial and lateral subdivisions. These results suggest that the chewing alleviates the PAG (dorsolateral and ventrolateral subdivisions) responses to stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Comparison of stress-induced voiding phenomena in copper line–via structures with different dielectric materials

    International Nuclear Information System (INIS)

    Hou, Yuejin; Tan, Cher Ming

    2009-01-01

    The package level stress-induced voiding (SIV) test of Cu dual-damascene line–via structures is performed. Two different dielectrics, undoped silica glass (USG) and carbon doped oxide (CDO), are used in this work. After 1344 h of high temperature storage test, the resistance drift of USG interconnects is found to be much smaller than that of CDO interconnects and voids are located at the bottom of the via for both USG and CDO interconnects. However, horizontal voids grown along the via bottom is observed for USG interconnects, whilst voids are found to grow vertically along the via sidewall for CDO interconnects. The phenomena are explained using finite element analysis in this work, and the observed poor SIV performance for CDO interconnects is also explained. With this finite element analysis, the implications of different low-k dielectrics on SIV reliability are discussed

  17. Lipopolysaccharide-binding protein and leptin are associated with stress-induced interleukin-6 cytokine expression ex vivo in obesity.

    Science.gov (United States)

    Huang, Chun-Jung; Stewart, Jennifer K; Shibata, Yoshimi; Slusher, Aaron L; Acevedo, Edmund O

    2015-05-01

    Obesity is associated with enhanced inflammation and mental stress, but limited information has addressed the potential additive effect of psychological stress on obesity-associated inflammation. This study examined whether obese subjects would elicit a greater host immune response (IL-6 mRNA and cytokine) to lipopolysaccharide (LPS) in response to mental stress. Blood samples for LPS-stimulated IL-6 mRNA and cytokine were collected prior to and following mental stress. Results showed that obese subjects elicited a greater LPS-induced IL-6 along with its mRNA expression following mental stress compared to normal-weight subjects. Stress-induced IL-6 cytokine response to LPS was correlated with the baseline levels of plasma LPS binding protein (LBP) and leptin. These findings are consistent with the idea that endogenous inflammatory agents (e.g., LBP and leptin), often elevated with obesity, enhance inflammatory responses to psychological stress. © 2014 Society for Psychophysiological Research.

  18. Direct evidence for stress-induced transformation between coexisting multiple martensites in a Ni–Mn–Ga multifunctional alloy

    International Nuclear Information System (INIS)

    Huang, L; Cong, D Y; Dong, Y H; Zhang, Y; Wang, Y D; Wang, Z L; Nie, Z H; Ren, Y

    2015-01-01

    The structural response of coexisting multiple martensites to stress field in a Ni–Mn–Ga multifunctional alloy was investigated by the in situ high-energy x-ray diffraction technique. Stress-induced transformation between coexisting multiple martensites was observed at 110 K, at which five-layered modulated (5M), seven-layered modulated (7M) and non-modulated (NM) martensites coexist. We found that a tiny stress of as low as 0.5 MPa could trigger the transformation from 5M and 7M martensites to NM martensite and this transformation is partly reversible. Besides the transformation between coexisting multiple martensites, rearrangement of martensite variants also occurs during loading, at least at high stress levels. The present study is instructive for designing advanced multifunctional alloys with easy actuation. (paper)

  19. Measurement of lattice rotations and internal stresses in over one hundred individual grains during a stress-induced martensitic transformation

    Directory of Open Access Journals (Sweden)

    Hachi Younes El

    2015-01-01

    Full Text Available To better understand the properties of polycrystals at a microscopic scale during cyclic mechanical loading we have measured the relationship between grain orientations, their positions inside the sample and their internal stresses. In this work, in-situ 3DXRD technique was performed on over hundred grains during the stress-induced martensitic transformation in a Cu-Al-Be shape memory alloy. Information about the position, orientation, and stress field was obtained for each austenitic grain. These results have been used to develop a procedure that allows automatic processing for a large number of grains, matching them during loading and leads to a quantitative stress field. A strong heterogeneity of stress state between the grains at the surface and in the volume is evident.

  20. Effect of Si on the reversibility of stress-induced martensite in Fe-Mn-Si shape memory alloys

    International Nuclear Information System (INIS)

    Stanford, N.; Dunne, D.P.

    2010-01-01

    Fe-Mn-Si is a well-characterized ternary shape memory alloy. Research on this alloy has consistently shown that the addition of 5-6 wt.% Si is desirable to enhance the reversibility of stress-induced martensite vis-a-vis shape memory. This paper examines the effect of Si on the morphology and the crystallography of the martensite in the Fe-Mn-Si system. It is concluded that the addition of Si increases the c/a ratio of the martensite, reduces the transformation volume change and decreases the atomic spacing difference between the parallel close-packed directions in the austenite-martensite interface (habit) plane. It is proposed that, in addition to austenite strengthening, Si enhances reversibility by reducing the volume change and the interfacial atomic mismatch between the martensite and the austenite. Although shape memory is improved, transformation reversibility remains limited by the necessary misfit dislocations that accommodate the atomic spacing differences in the interface.

  1. Experimental investigation of localized stress-induced leakage current distribution in gate dielectrics using array test circuit

    Science.gov (United States)

    Park, Hyeonwoo; Teramoto, Akinobu; Kuroda, Rihito; Suwa, Tomoyuki; Sugawa, Shigetoshi

    2018-04-01

    Localized stress-induced leakage current (SILC) has become a major problem in the reliability of flash memories. To reduce it, clarifying the SILC mechanism is important, and statistical measurement and analysis have to be carried out. In this study, we applied an array test circuit that can measure the SILC distribution of more than 80,000 nMOSFETs with various gate areas at a high speed (within 80 s) and a high accuracy (on the 10-17 A current order). The results clarified that the distributions of localized SILC in different gate areas follow a universal distribution assuming the same SILC defect density distribution per unit area, and the current of localized SILC defects does not scale down with the gate area. Moreover, the distribution of SILC defect density and its dependence on the oxide field for measurement (E OX-Measure) were experimentally determined for fabricated devices.

  2. Response of hippocampal mossy fiber zinc to excessive glutamate release.

    Science.gov (United States)

    Takeda, Atsushi; Minami, Akira; Sakurada, Naomi; Nakajima, Satoko; Oku, Naoto

    2007-01-01

    The response of hippocampal mossy fiber zinc to excessive glutamate release was examined to understand the role of the zinc in excessive excitation in the hippocampus. Extracellular zinc and glutamate concentrations during excessive stimulation with high K(+) were compared between the hippocampal CA3 and CA1 by the in vivo microdialysis. Zinc concentration in the CA3 was more increased than that in the CA1, while glutamate concentration in the CA3 was less increased than that in the CA1. It is likely that more increase in extracellular zinc is linked with less increase in extracellular glutamate in the CA3. To see zinc action in mossy fiber synapses during excessive excitation, furthermore, 1mM glutamate was regionally delivered to the stratum lucidum in the presence of zinc or CaEDTA, a membrane-impermeable zinc chelator, and intracellular calcium signal was measured in the CA3 pyramidal cell layer. The persistent increase in calcium signal during stimulation with glutamate was significantly attenuated in the presence of 100 microM zinc, while significantly enhanced in the presence of 1mM CaEDTA. These results suggest that zinc released from mossy fibers attenuates the increase in intracellular calcium signal in mossy fiber synapses and postsynaptic CA3 neurons after excessive inputs to dentate granular cells.

  3. The Effect of Citalopram on Midbrain CRF Receptors 1 and 2 in a Primate Model of Stress-Induced Amenorrhea

    Science.gov (United States)

    Senashova, Olga; Reddy, Arubala P.; Cameron, Judy L.; Bethea, Cynthia L.

    2012-01-01

    We have demonstrated marked differences in the neurobiology of the serotonin system between stress-sensitive (SS) and stress-resilient (SR) cynomolgus macaques characterized in a model of stress-induced amenorrhea, also called functional hypothalamic amenorrhea (FHA). Dysfunction of the serotonin system in SS monkeys suggested that administration of a selective serotonin reuptake inhibitor (SSRI) might correct FHA. This study examines the effect of escitalopram (CIT) administration to SS and SR monkeys on corticotrophin-releasing factor (CRF) receptor 1 (CRF-R1) and CRF receptor 2 (CRF-R2) gene expression in the serotonin cell body region of the midbrain dorsal raphe. CRF-R1 was not significantly different between groups. There was a significant effect of treatment and a significant interaction between treatment and stress sensitivity on the average CRF-R2-positive pixel area (P < .004 and P < .006, respectively) and on the average number of CRF-R2-positive cells (P < .023 and P < .025, respectively). CIT significantly increased CRF-R2-positive pixel area and cell number in the SS group (pixel area P < .001; cell number P < .01; Bonferoni) but not in the SR group. In summary, CIT administration tended to decrease CRF-R1, but the small animal number precluded significance. CIT administration significantly increased CRF-R2 only in SS animals. These data suggest that the administration of CIT reduces anxiogenic components and increases anxiolytic components of the CRF system in the midbrain serotonin network, which in turn leads to improved ovarian function. Moreover, these data raise the possibility that SSRIs may be effective in the treatment of stress-induced infertility. PMID:22412189

  4. Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

    Science.gov (United States)

    Downs, C A; McDougall, Kathleen E; Woodley, Cheryl M; Fauth, John E; Richmond, Robert H; Kushmaro, Ariel; Gibb, Stuart W; Loya, Yossi; Ostrander, Gary K; Kramarsky-Winter, Esti

    2013-01-01

    Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

  5. Stress-induced enhancement of mouse amygdalar synaptic plasticity depends on glucocorticoid and ß-adrenergic activity.

    Directory of Open Access Journals (Sweden)

    Ratna Angela Sarabdjitsingh

    Full Text Available BACKGROUND: Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the effects of stress on LTP in the LA-BLA pathway and the specific roles of corticosteroid and β-adrenergic receptor activation in this process. PRINCIPAL FINDINGS: Exposure to 20 min of restraint stress (compared to control treatment prior to slice preparation enhanced subsequent LTP induction in vitro, without affecting baseline fEPSP responses. The role of glucocorticoid receptors, mineralocorticoid receptors and β2-adrenoceptors in the effects of stress was studied by treating mice with the antagonists mifepristone, spironolactone or propranolol respectively (or the corresponding vehicles prior to stress or control treatment. In undisturbed controls, mifepristone and propranolol administration in vivo did not influence LTP induced in vitro. By contrast, spironolactone caused a gradually attenuating form of LTP, both in unstressed and stressed mice. Mifepristone treatment prior to stress strongly reduced the ability to induce LTP in vitro. Propranolol normalized the stress-induced enhancement of LTP to control levels during the first 10 min after high frequency stimulation, after which synaptic responses further declined. CONCLUSIONS: Acute stress changes BLA electrical properties such that subsequent LTP induction is facilitated. Both β-adrenergic and glucocorticoid receptors are involved in the development of these changes. Mineralocorticoid receptors are important for the maintenance of LTP in the BLA, irrespective of stress-induced changes in the

  6. Peroxisome proliferator-activated receptor delta (PPARdelta) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis.

    Science.gov (United States)

    Pesant, Matthieu; Sueur, Stéphanie; Dutartre, Patrick; Tallandier, Mireille; Grimaldi, Paul A; Rochette, Luc; Connat, Jean-Louis

    2006-02-01

    Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARdelta remains poorly studied. We focused on PPARdelta function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARdelta is the predominantly expressed isotype whereas PPARalpha was weakly detected. By performing cell viability assays, we also showed that the selective PPARdelta agonist GW501516 protected cells from H(2)O(2)-induced cell death. The protective effect of GW501516 was due to an inhibition of H(2)O(2)-triggered apoptosis as shown by annexin-V labeling, DNA fragmentation analysis, and caspase-3 activity measurement. We demonstrated by transient transfection of a dominant negative mutant of PPARdelta that the protection induced by GW501516 was totally dependent on PPARdelta. Semi-quantitative RT-PCR and Western blotting analysis demonstrated that GW501516 treatment upregulated catalase. Moreover, forced overexpression of catalase inhibited H(2)O(2)-triggered apoptosis, as evidenced by annexin-V labeling. Taken together, our results account for an important role of PPARdelta in inhibiting the onset of oxidative stress-induced apoptosis in H9c2 cells. PPARdelta appears to be a new therapeutic target for the regulation of heart reperfusion-associated oxidative stress and stimulation of enzymatic antioxidative defences.

  7. ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

    Science.gov (United States)

    Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

    2015-02-01

    Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

  8. Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Ralevski, Elizabeth; Southwick, Steven; Jackson, Eric; Jane, Jane Serrita; Russo, Melanie; Petrakis, Ismene

    2016-08-01

    Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the

  9. Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

    Science.gov (United States)

    Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

    2014-05-01

    Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

  10. Estrogen Receptor β Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.

    Science.gov (United States)

    Crider, Amanda; Nelson, Tyler; Davis, Talisha; Fagan, Kiley; Vaibhav, Kumar; Luo, Matthew; Kamalasanan, Sunay; Terry, Alvin V; Pillai, Anilkumar

    2018-02-12

    Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors. The ER is an organelle that serves essential roles in protein modification, folding, and maturation of proteins; however, the specific role of ER stress in altered social behavior is unknown. In this study, treatment with tunicamycin, an ER stress inducer, enhanced the phosphorylation level of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1) and increased X-box-binding protein 1 (XBP1) mRNA splicing activity in the mouse PFC, whereas inhibition of IRE1/XBP1 pathway in PFC by a viral particle approach attenuated social behavioral deficits caused by tunicamycin treatment. Reduced estrogen receptor beta (ERβ) protein levels were found in the PFC of male mice following tunicamycin treatment. Pretreatment with an ERβ specific agonist, ERB-041 significantly attenuated tunicamycin-induced deficits in social behavior, and activation of IRE1/XBP1 pathway in mouse PFC. Moreover, ERB-041 inhibited tunicamycin-induced increases in functional connectivity between PFC and hippocampus in male mice. Together, these results show that ERβ agonist attenuates ER stress-induced deficits in social behavior through the IRE-1/XBP1 pathway.

  11. BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

    Science.gov (United States)

    Nowacka, Marta; Obuchowicz, Ewa

    2013-01-01

    Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

  12. Wheat chloroplast targeted sHSP26 promoter confers heat and abiotic stress inducible expression in transgenic Arabidopsis Plants.

    Directory of Open Access Journals (Sweden)

    Neetika Khurana

    Full Text Available The small heat shock proteins (sHSPs have been found to play a critical role in physiological stress conditions in protecting proteins from irreversible aggregation. To characterize the hloroplast targeted sHSP26 promoter in detail, deletion analysis of the promoter is carried out and analysed via transgenics in Arabidopsis. In the present study, complete assessment of the importance of CCAAT-box elements along with Heat shock elements (HSEs in the promoter of sHSP26 was performed. Moreover, the importance of 5' untranslated region (UTR has also been established in the promoter via Arabidopsis transgenics. An intense GUS expression was observed after heat stress in the transgenics harbouring a full-length promoter, confirming the heat-stress inducibility of the promoter. Transgenic plants without UTR showed reduced GUS expression when compared to transgenic plants with UTR as was confirmed at the RNA and protein levels by qRT-PCR and GUS histochemical assays, thus suggesting the possible involvement of some regulatory elements present in the UTR in heat-stress inducibility of the promoter. Promoter activity was also checked under different abiotic stresses and revealed differential expression in different deletion constructs. Promoter analysis based on histochemical assay, real-time qPCR and fluorimetric analysis revealed that HSEs alone could not transcribe GUS gene significantly in sHSP26 promoter and CCAAT box elements contribute synergistically to the transcription. Our results also provide insight into the importance of 5`UTR of sHsp26 promoter thus emphasizing the probable role of imperfect CCAAT-box element or some novel cis-element with respect to heat stress.

  13. Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

    Directory of Open Access Journals (Sweden)

    C A Downs

    Full Text Available Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex, usually by expulsion or xenophagy (symbiophagy of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2 s(-1 PAR at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

  14. C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.

    Science.gov (United States)

    Mo, Hongyan; Wu, Qinyu; Miao, Jinhua; Luo, Congwei; Hong, Xue; Wang, Yongping; Tang, Lan; Hou, Fan Fan; Liu, Youhua; Zhou, Lili

    2017-08-20

    Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (SDF-1α), in mediating oxidative stress-induced podocyte injury. In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by malondialdehyde assay, nitrotyrosine staining and secretion of 8-hydroxy-2'-deoxyguanosine in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase. CXCR4 was also induced in human kidney biopsies with proteinuric kidney diseases and colocalized with advanced oxidation protein products (AOPPs), an established oxidative stress trigger. Using cultured podocytes and mouse model, we found that AOPPs induced significant loss of podocyte marker Wilms tumor 1 (WT1), nephrin, and podocalyxin, accompanied by upregulation of desmin both in vitro and in vivo. Furthermore, AOPPs worsened proteinuria and aggravated glomerulosclerosis in ADR. These effects were associated with marked activation of SDF-1α/CXCR4 axis in podocytes. Administration of AMD3100, a specific inhibitor of CXCR4, reduced proteinuria and ameliorated podocyte dysfunction and renal fibrosis triggered by AOPPs in mice. In glomerular miniorgan culture, AOPPs also induced CXCR4 expression and downregulated nephrin and WT1. Innovation and Conclusion: These results suggest that chemokine receptor CXCR4 plays a crucial role in mediating oxidative stress-induced podocyte injury, proteinuria, and renal fibrosis. CXCR4 could be a new target for mitigating podocyte injury, proteinuria, and glomerular sclerosis in proteinuric chronic kidney disease. Antioxid. Redox Signal. 27, 345-362.

  15. Persistent ER stress induces the spliced leader RNA silencing pathway (SLS, leading to programmed cell death in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Hanoch Goldshmidt

    2010-01-01

    Full Text Available Trypanosomes are parasites that cycle between the insect host (procyclic form and mammalian host (bloodstream form. These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR. However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS pathway. SLS elicits shut-off of spliced leader RNA (SL RNA transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD, evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS production, increase in cytoplasmic Ca(2+, and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM. ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes.

  16. Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

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    Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

    2016-01-01

    Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR