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Sample records for stress-induced ca3 dendritic

  1. Somal and dendritic development of human CA3 pyramidal neurons from midgestation to middle childhood: a quantitative Golgi study.

    Science.gov (United States)

    Lu, Dahua; He, Lixin; Xiang, Wei; Ai, Wei-Min; Cao, Ye; Wang, Xiao-Sheng; Pan, Aihua; Luo, Xue-Gang; Li, Zhiyuan; Yan, Xiao-Xin

    2013-01-01

    The CA3 area serves a key relay on the tri-synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre- and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi-impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age-dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood. Copyright © 2012 Wiley Periodicals, Inc.

  2. Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress

    NARCIS (Netherlands)

    Kole, MHP; Czeh, B; Fuchs, E

    2004-01-01

    The experience of chronic stress induces a reversible regression of hippocampal CA3 apical neuron dendrites. Although such postsynaptic membrane reduction will obviously diminish the possibility of synaptic input, the consequences for the functional membrane properties of these cells are not well

  3. Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

    International Nuclear Information System (INIS)

    Tsurugizawa, Tomokazu; Mukai, Hideo

    2005-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ERα agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ERβ agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ERα was performed using purified RC-19 antibody. The localization of ERα (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ERα and MAP kinase

  4. Stress-induced grey matter loss determined by MRI is primarily due to loss of dendrites and their synapses.

    Science.gov (United States)

    Kassem, Mustafa S; Lagopoulos, Jim; Stait-Gardner, Tim; Price, William S; Chohan, Tariq W; Arnold, Jonathon C; Hatton, Sean N; Bennett, Maxwell R

    2013-04-01

    Stress, unaccompanied by signs of post-traumatic stress disorder, is known to decrease grey matter volume (GMV) in the anterior cingulate cortex (ACC) and hippocampus but not the amygdala in humans. We sought to determine if this was the case in stressed mice using high-resolution magnetic resonance imaging (MRI) and to identify the cellular constituents of the grey matter that quantitatively give rise to such changes. Stressed mice showed grey matter losses of 10 and 15 % in the ACC and hippocampus, respectively but not in the amygdala or the retrosplenial granular area (RSG). Concurrently, no changes in the number or volumes of the somas of neurons, astrocytes or oligodendrocytes were detected. A loss of synaptic spine density of up to 60 % occurred on different-order dendrites in the ACC and hippocampus (CA1) but not in the amygdala or RSG. The loss of spines was accompanied by decreases in cumulative dendritic length of neurons of over 40 % in the ACC and hippocampus (CA1) giving rise to decreases in volume of dendrites of 2.6 mm(3) for the former and 0.6 mm(3) for the latter, with no change in the amygdala or RSG. These values are similar to the MRI-determined loss of GMV following stress of 3.0 and 0.8 mm(3) in ACC and hippocampus, respectively, with no changes in the amygdala or RSG. This quantitative study is the first to relate GMV changes in the cortex measured with MRI to volume changes in cellular constituents of the grey matter.

  5. Stress-induced buried waveguides in the 0.8CaSiO3–0.2Ca3(PO4)2 eutectic glass doped with Nd3+ ions

    International Nuclear Information System (INIS)

    Sola, D.; Martínez de Mendibil, J.; Vázquez de Aldana, J.R.; Lifante, G.; Balda, R.; Aza, A.H. de; Pena, P.; Fernández, J.

    2013-01-01

    In this work the fabrication of buried optical waveguides by femtosecond laser inscription in the 0.8CaSiO 3 –0.2Ca 3 (PO 4 ) 2 eutectic glass doped with Nd 3+ ions is reported. The glass samples were prepared by melting the eutectic powder mixture in a Pt–10 wt.% Rh crucible at 1600 °C and pouring it in a preheated brass mould. Afterwards, the glass was annealed to release the inner stresses. Buried waveguides were fabricated by focusing beneath the surface a pulsed Ti:sapphire laser with a pulsewidth of 120 fs working at 1 kHz. Two adjacent parallel tracks were written to define a region where an increase in the refractive index occurs. The effects produced by the variation of the laser pulse energy as well as the lateral separation between tracks, scanning speed and focusing distance were studied. After the laser processing, the near-field intensity distribution at 633 nm of the waveguide's modes was studied demonstrating the confinement of both, the TE as the TM polarizations. In order to diminish the losses induced by colour centres absorption, heat treatments were carried out in the samples. The waveguide's modes were compared with respect to the samples without heat treatments. The spectroscopic properties of the neodymium ions have been characterized to evaluate in what extent their optical properties could be modified by the waveguide fabrication process and to elucidate the potential application of such waveguides as integrated laser sources.

  6. 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.

  7. Electroconvulsive stimulations prevent stress-induced morphological changes in the hippocampus

    DEFF Research Database (Denmark)

    Hageman, I; Nielsen, M; Wörtwein, Gitta

    2008-01-01

    whether repeated electroconvulsive stimulations (ECSs) could influence such changes in stressed rats. Furthermore, we investigated whether ECSs per se could influence neuronal branching and total length of the CA3 hippocampal neuronal dendritic tree in normal rats. Rats were stressed using the 21-day 6 h...

  8. Reactivation of Rate Remapping in CA3.

    Science.gov (United States)

    Schwindel, C Daniela; Navratilova, Zaneta; Ali, Karim; Tatsuno, Masami; McNaughton, Bruce L

    2016-09-07

    The hippocampus is thought to contribute to episodic memory by creating, storing, and reactivating patterns that are unique to each experience, including different experiences that happen at the same location. Hippocampus can combine spatial and contextual/episodic information using a dual coding scheme known as "global" and "rate" remapping. Global remapping selects which set of neurons can activate at a given location. Rate remapping readjusts the firing rates of this set depending on current experience, thus expressing experience-unique patterns at each location. But can the experience-unique component be retrieved spontaneously? Whereas reactivation of recent, spatially selective patterns in hippocampus is well established, it is never perfect, raising the issue of whether the experiential component might be absent. This question is key to the hypothesis that hippocampus can assist memory consolidation by reactivating and broadcasting experience-specific "index codes" to neocortex. In CA3, global remapping exhibits attractor-like dynamics, whereas rate remapping apparently does not, leading to the hypothesis that only the former can be retrieved associatively and casting doubt on the general consolidation hypothesis. Therefore, we studied whether the rate component is reactivated spontaneously during sleep. We conducted neural ensemble recordings from CA3 while rats ran on a circular track in different directions (in different sessions) and while they slept. It was shown previously that the two directions of running result in strong rate remapping. During sleep, the most recent rate distribution was reactivated preferentially. Therefore, CA3 can retrieve patterns spontaneously that are unique to both the location and the content of recent experience. The hippocampus is required for memory of events and their spatial contexts. The primary correlate of hippocampal activity is location in space, but multiple memories can occur in the same location. To be useful

  9. Insomnia severity is associated with a decreased volume of the CA3/Dentate Gyrus Hippocampal Subfield

    Science.gov (United States)

    Neylan, Thomas C.; Mueller, Susanne G.; Wang, Zhen; Metzler, Thomas J.; Lenoci, Maryann; Truran, Diana; Marmar, Charles R.; Weiner, Michael W.; Schuff, Norbert

    2010-01-01

    Background Prolonged disruption of sleep in animal studies is associated with decreased neurogenesis in the dentate gyrus. Our objective was to determine if insomnia severity in a sample of PTSD and controls was associated with decreased volume in the CA3/dentate hippocampal subfield. Methods Volumes of hippocampal subfields in seventeen veteran males positive for PTSD (41 ±12 years) and nineteen age-matched male veterans negative for PTSD were measured using 4 Tesla MRI. Subjective sleep quality was measured by the Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI). Results Higher scores on the ISI, indicating worse insomnia, were associated with smaller volumes of the CA3/dentate subfields (r= −.48, p < 0.01) in the combined sample. Adding the ISI score as a predictor for CA3/dentate volume to a hierarchical linear regression model after first controlling for age and PTSD symptoms accounted for a 13 % increase in incremental variance (t= −2.47, p= 0.02). Conclusions The findings indicate for the first time in humans that insomnia severity is associated with volume loss of the CA3/dentate subfields. This is consistent with animal studies showing that chronic sleep disruption is associated with decreased neurogenesis and dendritic branching in these structures. PMID:20598672

  10. Neuropeptide Y and nestin expression in the hippocampal CA3 region following restrained and inverted stress in rats

    Institute of Scientific and Technical Information of China (English)

    Guogang Sun; Ailing Li; Bo Chen; Guangbi Fan; Hongwen Xiao; Yue Chen; Jie Xu; Ye Nie; Bing Zhang; Lin Gong

    2011-01-01

    Our preliminary study demonstrated that neuropeptide Y (NPY)/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits, as well as sustained cerebral injury in the adult hippocampus.

  11. Stress-Induced Neurodegeneration: Mechanisms and Interventions

    National Research Council Canada - National Science Library

    Meyerhoff, James

    2000-01-01

    .... chronic stress in several species, including mouse, rat, tree shrew and monkey, have been reported to develop alterations in hippocampal morphology, including apical dendritic atrophy, depletion...

  12. 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

  13. 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, ...

  14. Neuronal migration and its disorders affecting the CA3 region

    Directory of Open Access Journals (Sweden)

    Richard eBelvindrah

    2014-03-01

    Full Text Available In this review, we focus on CA3 neuronal migration disorders in the rodent. We begin by introducing the main steps of hippocampal development, and we summarize characteristic hippocampal malformations in human. We then describe various mouse mutants showing structural hippocampal defects. Notably, genes identified in human cortical neuronal migration disorders consistently give rise to a CA3 phenotype when mutated in the mouse. We successively describe their molecular, physiological and behavioral phenotypes that together contribute to a better understanding of CA3-dependent functions. We finally discuss potential factors underlying the CA3 vulnerability revealed by these mouse mutants and that may also contribute to other human neurological and psychiatric disorders.

  15. 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

  16. Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling.

    Science.gov (United States)

    Fernández-Ruiz, Antonio; Oliva, Azahara; Nagy, Gergő A; Maurer, Andrew P; Berényi, Antal; Buzsáki, György

    2017-03-08

    Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons. The theta-phase preference and excitatory strength of the afferent CA3 and entorhinal inputs effectively timed the principal neuron activity, as well as regulated distinct CA1 interneuron populations in multiple tasks and behavioral states. Feedback potentiation of distal dendritic inhibition by CA1 place cells attenuated the excitatory entorhinal input at place field entry, coupled with feedback depression of proximal dendritic and perisomatic inhibition, allowing the CA3 input to gain control toward the exit. Thus, upstream inputs interact with local mechanisms to determine theta-phase timing of hippocampal neurons to support memory and spatial navigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear glucocorticoid receptor in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Miyuki eYoshiya

    2013-11-01

    Full Text Available Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes.We demonstrated rapid effects (~ 1 h of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500 and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR, abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100-1000 nM might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.

  18. [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.

  19. 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.

  20. Place cell rate remapping by CA3 recurrent collaterals.

    Directory of Open Access Journals (Sweden)

    Trygve Solstad

    2014-06-01

    Full Text Available Episodic-like memory is thought to be supported by attractor dynamics in the hippocampus. A possible neural substrate for this memory mechanism is rate remapping, in which the spatial map of place cells encodes contextual information through firing rate variability. To test whether memories are stored as multimodal attractors in populations of place cells, recent experiments morphed one familiar context into another while observing the responses of CA3 cell ensembles. Average population activity in CA3 was reported to transition gradually rather than abruptly from one familiar context to the next, suggesting a lack of attractive forces associated with the two stored representations. On the other hand, individual CA3 cells showed a mix of gradual and abrupt transitions at different points along the morph sequence, and some displayed hysteresis which is a signature of attractor dynamics. To understand whether these seemingly conflicting results are commensurate with attractor network theory, we developed a neural network model of the CA3 with attractors for both position and discrete contexts. We found that for memories stored in overlapping neural ensembles within a single spatial map, position-dependent context attractors made transitions at different points along the morph sequence. Smooth transition curves arose from averaging across the population, while a heterogeneous set of responses was observed on the single unit level. In contrast, orthogonal memories led to abrupt and coherent transitions on both population and single unit levels as experimentally observed when remapping between two independent spatial maps. Strong recurrent feedback entailed a hysteretic effect on the network which diminished with the amount of overlap in the stored memories. These results suggest that context-dependent memory can be supported by overlapping local attractors within a spatial map of CA3 place cells. Similar mechanisms for context-dependent memory may

  1. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    Science.gov (United States)

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  2. Spontaneous release from mossy fiber terminals inhibits Ni2+-sensitive T-type Ca2+ channels of CA3 pyramidal neurons in the rat organotypic hippocampal slice.

    Science.gov (United States)

    Reid, Christopher A; Xu, Shenghong; Williams, David A

    2008-01-01

    Mossy fibers (axons arising from dentate granule cells) form large synaptic contacts exclusively onto the proximal apical dendrites of CA3 pyramidal neurons. They can generate large synaptic currents that occur in close proximity to the soma. These properties mean that active conductance in the proximal apical dendrite could have a disproportionate influence on CA3 pyramidal neuron excitability. Ni(2+)-sensitive T-type Ca(2+) channels are important modulators of dendritic excitability. Here, we use an optical approach to determine the contribution of Ni(2+) (100 microM)-sensitive Ca(2+) channels to action potential (AP) elicited Ca(2+) flux in the soma, proximal apical and distal apical dendrites. At resting membrane potentials Ni(2+)-sensitive Ca(2+) channels do not contribute to the Ca(2+) signal in the proximal apical dendrite, but do contribute in the other cell regions. Spontaneous release from mossy fiber terminals acting on 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive postsynaptic channels underlies a tonic inhibition of Ni(2+)-sensitive channels. Chelating Zn(2+) with CaEDTA blocks CNQX-sensitive changes in Ca(2+) flux implicating a mechanistic role of this ion in T-type Ca(2+) channel block. To test if this inhibition influenced excitability, progressively larger depolarizing pulses were delivered to CA3 pyramidal neurons. CNQX significantly reduced the size of the depolarizing step required to generate APs and increased the absolute number of APs per depolarizing step. This change in AP firing was completely reversed by the addition of Ni(2+). This mechanism may reduce the impact of T-type Ca(2+) channels in a region where large synaptic events are common.

  3. 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.

  4. A role for CA3 in social recognition memory.

    Science.gov (United States)

    Chiang, Ming-Ching; Huang, Arthur J Y; Wintzer, Marie E; Ohshima, Toshio; McHugh, Thomas J

    2018-02-02

    Social recognition memory is crucial for survival across species, underlying the need to correctly identify conspecifics, mates and potential enemies. In humans the hippocampus is engaged in social and episodic memory, however the circuit mechanisms of social memory in rodent models has only recently come under scrutiny. Work in mice has established that the dorsal CA2 and ventral CA1 regions play critical roles, however a more comprehensive comparative analyses of the circuits and mechanisms required has not been reported. Here we employ conditional genetics to examine the differential contributions of the hippocampal subfields to social memory. We find that the deletion of NMDA receptor subunit 1 gene (NR1), which abolishes NMDA receptor synaptic plasticity, in CA3 pyramidal cells led to deficits in social memory; however, mice lacking the same gene in DG granule cells performed indistinguishable from controls. Further, we use conditional pharmacogenetic inhibition to demonstrate that activity in ventral, but not dorsal, CA3 is necessary for the encoding of a social memory. These findings demonstrated CA3 pyramidal cell plasticity and transmission contribute to the encoding of social stimuli and help further identify the distinct circuits underlying the role of the hippocampus in social memory. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.

    Science.gov (United States)

    Evstratova, Alesya; Tóth, Katalin

    2011-12-01

    The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca(2+) wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca(2+) waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca(2+) signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca(2+) release from CA3 pyramidal cell internal stores.

  6. 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.

  7. Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

    OpenAIRE

    I?iguez, Sergio D.; Aubry, Antonio; Riggs, Lace M.; Alipio, Jason B.; Zanca, Roseanna M.; Flores-Ramirez, Francisco J.; Hernandez, Mirella A.; Nieto, Steven J.; Musheyev, David; Serrano, Peter A.

    2016-01-01

    Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes fo...

  8. 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

  9. Short-term environmental enrichment is sufficient to counter stress-induced anxiety and associated structural and molecular plasticity in basolateral amygdala.

    Science.gov (United States)

    Ashokan, Archana; Hegde, Akshaya; Mitra, Rupshi

    2016-07-01

    Moderate levels of anxiety enable individual animals to cope with stressors through avoidance, and could be an adaptive trait. However, repeated stress exacerbates anxiety to pathologically high levels. Dendritic remodeling in the basolateral amygdala is proposed to mediate potentiation of anxiety after stress. Similarly, modulation of brain-derived neurotrophic factor is thought to be important for the behavioral effects of stress. In the present study, we investigate if relatively short periods of environmental enrichment in adulthood can confer resilience against stress-induced anxiety and concomitant changes in neuronal arborisation and brain derived neurotrophic factor within basolateral amygdala. Two weeks of environmental enrichment countermanded the propensity of increased anxiety following chronic immobilization stress. Environmental enrichment concurrently reduced dendritic branching and spine density of projection neurons of the basolateral amygdala. Moreover, stress increased abundance of BDNF mRNA in the basolateral amygdala in agreement with the dendritic hypertrophy post-stress and role of BDNF in promoting dendritic arborisation. In contrast, environmental enrichment prevented stress-induced rise in the BDNF mRNA abundance. Gain in body weights and adrenal weights remained unaffected by exposure to environmental enrichment. These observations suggest that a short period of environmental enrichment can provide resilience against maladaptive effects of stress on hormonal, neuronal and molecular mediators of anxiogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons.

    Directory of Open Access Journals (Sweden)

    Fumiaki Fukushima

    Full Text Available Synchronized discharges in the hippocampal CA3 recurrent network are supposed to underlie network oscillations, memory formation and seizure generation. In the hippocampal CA3 network, NMDA receptors are abundant at the recurrent synapses but scarce at the mossy fiber synapses. We generated mutant mice in which NMDA receptors were abolished in hippocampal CA3 pyramidal neurons by postnatal day 14. The histological and cytological organizations of the hippocampal CA3 region were indistinguishable between control and mutant mice. We found that mutant mice lacking NMDA receptors selectively in CA3 pyramidal neurons became more susceptible to kainate-induced seizures. Consistently, mutant mice showed characteristic large EEG spikes associated with multiple unit activities (MUA, suggesting enhanced synchronous firing of CA3 neurons. The electrophysiological balance between fast excitatory and inhibitory synaptic transmission was comparable between control and mutant pyramidal neurons in the hippocampal CA3 region, while the NMDA receptor-slow AHP coupling was diminished in the mutant neurons. In the adult brain, inducible ablation of NMDA receptors in the hippocampal CA3 region by the viral expression vector for Cre recombinase also induced similar large EEG spikes. Furthermore, pharmacological blockade of CA3 NMDA receptors enhanced the susceptibility to kainate-induced seizures. These results raise an intriguing possibility that hippocampal CA3 NMDA receptors may suppress the excitability of the recurrent network as a whole in vivo by restricting synchronous firing of CA3 neurons.

  11. 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....

  12. A process analysis of the CA3 subregion of the hippocampus

    Directory of Open Access Journals (Sweden)

    Raymond PIERRE Kesner

    2013-05-01

    Full Text Available AbstractFrom a behavioral perspective the CA3a,b subregion of the hippocampus plays an important role in the encoding of new spatial information within short-term memory with a duration of seconds and minutes. This can easily be observed in tasks that require rapid encoding, novelty detection, 1-trial short- term or working memory, and 1-trial cued recall primarily for spatial information. These are tasks that have been assumed to reflect the operations of episodic memory and require interactions between CA3a,b and the dentate gyrus via mossy fiber inputs into the CA3a,b. The CA3a,b is also important for encoding of spatial information requiring the acquisition of arbitrary and relational associations. All these tasks are assumed to operate within an autoassociative network function of the CA3 region. The CA3a,b also supports retrieval of short-term memory information based on a spatial pattern completion process. Based on afferent inputs into CA3a,b from the dentate gyrus (DG via mossy fibers and afferents from the entorhinal cortex into CA3a,b as well as reciprocal connections with the septum, CA3a,b can bias the process of encoding utilizing the operation of spatial pattern separation and the process of retrieval utilizing the operation of pattern completion. The CA3a,b also supports sequential processing of information in cooperation with CA1 based on the Schaffer collateral output from CA3a,b to CA1. The CA3c function is in part based on modulation of the DG in supporting pattern separation processes.

  13. Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons.

    Science.gov (United States)

    Sasaki, Takuya; Piatti, Verónica C; Hwaun, Ernie; Ahmadi, Siavash; Lisman, John E; Leutgeb, Stefan; Leutgeb, Jill K

    2018-02-01

    Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.

  14. Dendritic cell vaccines.

    Science.gov (United States)

    Mosca, Paul J; Lyerly, H Kim; Clay, Timothy M; Morse, Michael A; Lyerly, H Kim

    2007-05-01

    Dendritic cells are antigen-presenting cells that have been shown to stimulate tumor antigen-specific T cell responses in preclinical studies. Consequently, there has been intense interest in developing dendritic cell based cancer vaccines. A variety of methods for generating dendritic cells, loading them with tumor antigens, and administering them to patients have been described. In recent years, a number of early phase clinical trials have been performed and have demonstrated the safety and feasibility of dendritic cell immunotherapies. A number of these trials have generated valuable preliminary data regarding the clinical and immunologic response to DC-based immunotherapy. The emphasis of dendritic cell immunotherapy research is increasingly shifting toward the development of strategies to increase the potency of dendritic cell vaccine preparations.

  15. D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.

    Science.gov (United States)

    Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L

    2015-01-01

    Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Spatial information is preferentially processed by the distal part of CA3: implication for memory retrieval.

    Science.gov (United States)

    Flasbeck, Vera; Atucha, Erika; Nakamura, Nozomu H; Yoshida, Motoharu; Sauvage, Magdalena M

    2018-07-16

    For the past decades, CA3 was considered as a single functional entity. However, strong differences between the proximal (close to the dentate gyrus) and the distal (close to CA2) parts of CA3 in terms of connectivity patterns, gene expression and electrophysiological properties suggest that it is not the case. We recently showed that proximal CA3 (together with distal CA1) preferentially deals with non-spatial information [1]. In contrast to proximal CA3, distal CA3 mainly receives and predominantly projects to spatially tuned areas. Here, we tested if distal CA3 preferentially processes spatial information, which would suggest a segregation of the spatial information along the proximodistal axis of CA3. We used a high-resolution imaging technique based on the detection of the expression of the immediate-early gene Arc, commonly used to map activity in the medial temporal lobe. We showed that distal CA3 is strongly recruited in a newly designed delayed nonmatching-to-location task with high memory demands in rats, while proximal CA3 is not. These results indicate a functional segregation of CA3 that mirrors the one reported in CA1, and suggest the existence of a distal CA3- proximal CA1 spatial subnetwork. These findings bring further evidence for the existence of 'specialized' spatial and non-spatial subnetworks segregated along the proximodistal axis of the hippocampus and put forward the 'segregated' view of information processing in the hippocampus as a reasonable alternative to the well-accepted 'integrated' view, according to which spatial and non-spatial information are systematically integrated in the hippocampus to form episodic memory. Copyright © 2018. Published by Elsevier B.V.

  17. 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: ...

  18. 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.

  19. 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

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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

  4. Perforant path lesioning induces sprouting of CA3-associated fibre systems in mouse hippocampal formation

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Hegelund, Iørn V; Poulsen, Frantz R

    2002-01-01

    mice. We found that lesioning led to translaminar sprouting of Timm stained regio inferior hippocampus (CA3)-associated fibre systems into the denervated termination zones of the CA3 and dentate gyrus, from the adjacent non-denervated stratum radiatum of CA3. Differences were seen in the Timm staining...... pattern of the two strains of mice, while the response to lesioning appeared similar albeit less pronounced than that observed in the rat. We also observed an intensified acetylcholine esterase staining reflective of cholinergic sprouting in the denervated perforant path termination zones, which...... was particularly prominent in areas with sprouting of Timm stained CA3-associated fibres. Finally, we showed that some of the sprouting fibres within the CA3 were myelinated, due to an increased density of silver impregnated myelinated fibres in this region after lesioning. These results show that the basic...

  5. Observation of microstructure of hydrated Ca3SiO5

    International Nuclear Information System (INIS)

    Mori, Kazuhiro; Sato, Takashi; Fukunaga, Toshiharu; Oishi, Koji; Kimura, Katsuhiko; Iwase, Kenji; Sugiyama, Masaaki; Itoh, Keiji; Shikanai, Fumihito; Wuernisha, Tuerxun; Yonemura, Masao; Sulistyanintyas, Dyah; Tsukushi, Itaru; Takata, Shinich; Otomo, Toshiya; Kamiyma, Takashi; Kawai, Masayoshi

    2006-01-01

    Quasi-elastic neutron scattering experiments were carried out to evaluate the hydration rate of tricalcium silicate (Ca 3 SiO 5 ). Furthermore, in the early hydration period, a variation in surface roughness of Ca 3 SiO 5 was observed in nano-scale by the small-angle neutron scattering. From these results, it was found that the hydration rate of Ca 3 SiO 5 is suppressed when the surface of Ca 3 SiO 5 becomes rough through the creation of hydration products C-S-H gel and Ca(OH) 2 , and this roughness is associated with changes in the Ca 3 SiO 5 hydration rate

  6. The race to learn: spike timing and STDP can coordinate learning and recall in CA3.

    Science.gov (United States)

    Nolan, Christopher R; Wyeth, Gordon; Milford, Michael; Wiles, Janet

    2011-06-01

    The CA3 region of the hippocampus has long been proposed as an autoassociative network performing pattern completion on known inputs. The dentate gyrus (DG) region is often proposed as a network performing the complementary function of pattern separation. Neural models of pattern completion and separation generally designate explicit learning phases to encode new information and assume an ideal fixed threshold at which to stop learning new patterns and begin recalling known patterns. Memory systems are significantly more complex in practice, with the degree of memory recall depending on context-specific goals. Here, we present our spike-timing separation and completion (STSC) model of the entorhinal cortex (EC), DG, and CA3 network, ascribing to each region a role similar to that in existing models but adding a temporal dimension by using a spiking neural network. Simulation results demonstrate that (a) spike-timing dependent plasticity in the EC-CA3 synapses provides a pattern completion ability without recurrent CA3 connections, (b) the race between activation of CA3 cells via EC-CA3 synapses and activation of the same cells via DG-CA3 synapses distinguishes novel from known inputs, and (c) modulation of the EC-CA3 synapses adjusts the learned versus test input similarity required to evoke a direct CA3 response prior to any DG activity, thereby adjusting the pattern completion threshold. These mechanisms suggest that spike timing can arbitrate between learning and recall based on the novelty of each individual input, ensuring control of the learn-recall decision resides in the same subsystem as the learned memories themselves. The proposed modulatory signal does not override this decision but biases the system toward either learning or recall. The model provides an explanation for empirical observations that a reduction in novelty produces a corresponding reduction in the latency of responses in CA3 and CA1. Copyright © 2010 Wiley-Liss, Inc.

  7. How informative are spatial CA3 representations established by the dentate gyrus?

    Directory of Open Access Journals (Sweden)

    Erika Cerasti

    2010-04-01

    Full Text Available In the mammalian hippocampus, the dentate gyrus (DG is characterized by sparse and powerful unidirectional projections to CA3 pyramidal cells, the so-called mossy fibers. Mossy fiber synapses appear to duplicate, in terms of the information they convey, what CA3 cells already receive from entorhinal cortex layer II cells, which project both to the dentate gyrus and to CA3. Computational models of episodic memory have hypothesized that the function of the mossy fibers is to enforce a new, well-separated pattern of activity onto CA3 cells, to represent a new memory, prevailing over the interference produced by the traces of older memories already stored on CA3 recurrent collateral connections. Can this hypothesis apply also to spatial representations, as described by recent neurophysiological recordings in rats? To address this issue quantitatively, we estimate the amount of information DG can impart on a new CA3 pattern of spatial activity, using both mathematical analysis and computer simulations of a simplified model. We confirm that, also in the spatial case, the observed sparse connectivity and level of activity are most appropriate for driving memory storage-and not to initiate retrieval. Surprisingly, the model also indicates that even when DG codes just for space, much of the information it passes on to CA3 acquires a non-spatial and episodic character, akin to that of a random number generator. It is suggested that further hippocampal processing is required to make full spatial use of DG inputs.

  8. Thermodynamic, electronic, and magnetic properties of intrinsic vacancy defects in antiperovskite Ca3SnO

    Science.gov (United States)

    Batool, Javaria; Alay-e-Abbas, Syed Muhammad; Amin, Nasir

    2018-04-01

    The density functional theory based total energy calculations are performed to examine the effect of charge neutral and fully charged intrinsic vacancy defects on the thermodynamic, electronic, and magnetic properties of Ca3SnO antiperovskite. The chemical stability of Ca3SnO is evaluated with respect to binary compounds CaO, CaSn, and Ca2Sn, and the limits of atomic chemical potentials of Ca, Sn, and O atoms for stable synthesis of Ca3SnO are determined within the generalized gradient approximation parametrization scheme. The electronic properties of the pristine and the non-stoichiometric forms of this compound have been explored and the influence of isolated intrinsic vacancy defects (Ca, Sn, and O) on the structural, bonding, and electronic properties of non-stoichiometric Ca3SnO are analyzed. We also predict the possibility of achieving stable ferromagnetism in non-stoichiometric Ca3SnO by means of charge neutral tin vacancies. From the calculated total energies and the valid ranges of atomic chemical potentials, the formation energetics of intrinsic vacancy defects in Ca3SnO are evaluated for various growth conditions. Our results indicate that the fully charged calcium vacancies are thermodynamically stable under the permissible Sn-rich condition of stable synthesis of Ca3SnO, while tin and oxygen vacancies are found to be stable under the extreme Ca-rich condition.

  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. 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.

  11. 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...

  12. 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.

  13. 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.

  14. Dendritic Spines in Depression: What We Learned from Animal Models

    Directory of Open Access Journals (Sweden)

    Hui Qiao

    2016-01-01

    Full Text Available Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS, chronic unpredictable mild stress (CUMS, and chronic social defeat stress (CSDS, have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

  15. A signature of attractor dynamics in the CA3 region of the hippocampus.

    Directory of Open Access Journals (Sweden)

    César Rennó-Costa

    2014-05-01

    Full Text Available The notion of attractor networks is the leading hypothesis for how associative memories are stored and recalled. A defining anatomical feature of such networks is excitatory recurrent connections. These "attract" the firing pattern of the network to a stored pattern, even when the external input is incomplete (pattern completion. The CA3 region of the hippocampus has been postulated to be such an attractor network; however, the experimental evidence has been ambiguous, leading to the suggestion that CA3 is not an attractor network. In order to resolve this controversy and to better understand how CA3 functions, we simulated CA3 and its input structures. In our simulation, we could reproduce critical experimental results and establish the criteria for identifying attractor properties. Notably, under conditions in which there is continuous input, the output should be "attracted" to a stored pattern. However, contrary to previous expectations, as a pattern is gradually "morphed" from one stored pattern to another, a sharp transition between output patterns is not expected. The observed firing patterns of CA3 meet these criteria and can be quantitatively accounted for by our model. Notably, as morphing proceeds, the activity pattern in the dentate gyrus changes; in contrast, the activity pattern in the downstream CA3 network is attracted to a stored pattern and thus undergoes little change. We furthermore show that other aspects of the observed firing patterns can be explained by learning that occurs during behavioral testing. The CA3 thus displays both the learning and recall signatures of an attractor network. These observations, taken together with existing anatomical and behavioral evidence, make the strong case that CA3 constructs associative memories based on attractor dynamics.

  16. Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

    Science.gov (United States)

    Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

    2017-01-01

    The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. SNAP-25 in hippocampal CA3 region is required for long-term memory formation

    International Nuclear Information System (INIS)

    Hou Qiuling; Gao Xiang; Lu Qi; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

    2006-01-01

    SNAP-25 is a synaptosomal protein of 25 kDa, a key component of synaptic vesicle-docking/fusion machinery, and plays a critical role in exocytosis and neurotransmitter release. We previously reported that SNAP-25 in the hippocampal CA1 region is involved in consolidation of contextual fear memory and water-maze spatial memory (Hou et al. European J Neuroscience, 20: 1593-1603, 2004). SNAP-25 is expressed not only in the CA1 region, but also in the CA3 region, and the SNAP-25 mRNA level in the CA3 region is higher than in the CA1 region. Here, we provide evidence that SNAP-25 in the CA3 region is also involved in learning/memory. Intra-CA3 infusion of SNAP-25 antisense oligonucleotide impaired both long-term contextual fear memory and water-maze spatial memory, with short-term memory intact. Furthermore, the SNAP-25 antisense oligonucleotide suppressed the long-term potentiation (LTP) of field excitatory post-synaptic potential (fEPSP) in the mossy-fiber pathway (DG-CA3 pathway), with no effect on paired-pulse facilitation of the fEPSP. These results are consistent with the notion that SNAP-25 in the hippocampal CA3 region is required for long-term memory formation

  18. Recurrent synapses and circuits in the CA3 region of the hippocampus: an associative network.

    Directory of Open Access Journals (Sweden)

    Richard eMiles

    2014-01-01

    Full Text Available In the CA3 region of the hippocampus, pyramidal cells excite other pyramidal cells and interneurons. The axons of CA3 pyramidal cells spread throughout most of the region to form an associative network. These connections were first drawn by Cajal and Lorente de No. Their physiological properties were explored to understand epileptiform discharges generated in the region. Synapses between pairs of pyramidal cells involve one or few release sites and are weaker than connections made by mossy fibres on CA3 pyramidal cells. Synapses with interneurons are rather effective, as needed to control unchecked excitation. We examine contributions of recurrent synapses to epileptiform synchrony, to the genesis of sharp waves in the CA3 region and to population oscillations at theta and gamma frequencies. Recurrent connections in CA3, as other associative cortices, have a lower connectivity spread over a larger area than in primary sensory cortices. This sparse, but wide-ranging connectivity serves the functions of an associative network, including acquisition of neuronal representations as activity in groups of CA3 cells and completion involving the recall from partial cues of these ensemble firing patterns.

  19. 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

  20. 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

  1. 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.

  2. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

    Science.gov (United States)

    Taylor, Caitlin A.; Yan, Jing; Howell, Audrey S.; Dong, Xintong; Shen, Kang

    2015-01-01

    The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1. PMID:26633194

  3. Naloxone injections into CA3 disrupt pattern completion associated with relapse from cocaine seeking

    Science.gov (United States)

    Kirk, Ryan A.; Clark, Jascha K.; Moore, Angela; Keefe, Kristen

    2016-01-01

    The goal of the present research was to assess the degree to which a pattern completion process operates in cue-induced relapse to cocaine-seeking behavior. Using a novel cue-preference version of the place preference task, rats were administered cocaine or saline, which resulted in a preference for the cocaine-paired cues. After 21 days of abstinence and prior to the preference test, for one group, PBS or naloxone was injected into the CA3 subregion of the hippocampus and for a second group, saline or naloxone was injected systemically. The results indicated that infusions of naloxone into CA3 or systemic injections produced a marked disruption for one and two cues, but had minimal disruptive effect for three or four cues, suggesting that naloxone injections disrupt CA3 function and trigger a deficit in a pattern completion process. Thus, it appears that cue-based activation of the dorsal CA3 might be a critical trigger via a pattern completion process. Based on additional analyses it appears that there is a disruption primarily for object touches for one cue naloxone injections into the CA3 or systemic injections, but no effect on time (spatial context). PMID:26815290

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Dendritic cell neoplasms: an overview.

    Science.gov (United States)

    Kairouz, Sebastien; Hashash, Jana; Kabbara, Wadih; McHayleh, Wassim; Tabbara, Imad A

    2007-10-01

    Dendritic cell neoplasms are rare tumors that are being recognized with increasing frequency. They were previously classified as lymphomas, sarcomas, or histiocytic neoplasms. The World Health Organization (WHO) classifies dendritic cell neoplasms into five groups: Langerhans' cell histiocytosis, Langerhans' cell sarcoma, Interdigitating dendritic cell sarcoma/tumor, Follicular dendritic cell sarcoma/tumor, and Dendritic cell sarcoma, not specified otherwise (Jaffe, World Health Organization classification of tumors 2001; 273-289). Recently, Pileri et al. provided a comprehensive immunohistochemical classification of histiocytic and dendritic cell tumors (Pileri et al., Histopathology 2002;59:161-167). In this article, a concise overview regarding the pathological, clinical, and therapeutic aspects of follicular dendritic, interdigitating dendritic, and Langerhans' cell tumors is presented.

  11. Bi4Sr3Ca3Cu4O16 galss and superconducting glass ceramics

    International Nuclear Information System (INIS)

    Zheng, H.; Mackenzie, J.D.

    1988-01-01

    Bi 4 Sr 3 Ca 3 Cu 4 O 16 glass has been successfully fabricated by the melting process. Glass transition temperature, crystallization temperature, and liquid temperature of the glass are 434, 478, and 833 0 C, respectively. After the glass is heat treated at 800 0 C, a glass ceramic is formed. A comparison of the x-ray-diffraction pattern of the superconducting Bi 4 Sr 3 Ca 3 Cu 4 O/sub 16+//sub x/ ceramic to the Bi 4 Sr 3 Ca 3 Cu 4 O 16 glass ceramic revealed preferred orientation in the glass ceramic crystals. The superconducting transition temperatures T/sub c//sub (onset)/ and T/sub c//sub (zero)/ of the glass ceramics are 100 and 45 K, respectively

  12. Thermal conductivity of Ca3Co2O6 single crystals

    Science.gov (United States)

    Che, H. L.; Shi, J.; Wu, J. C.; Rao, X.; Liu, X. G.; Zhao, X.; Sun, X. F.

    2018-05-01

    Ca3Co2O6 is a rare example of one-dimensional Ising spin-chain material with the moments preferentially aligned along the c axis. In this work, we study the c-axis thermal conductivity (κc) of Ca3Co2O6 single crystal at low temperatures down to 0.3 K and in magnetic fields up to 14 T. The zero-field κc(T) shows a large phonon peak and can be well fitted by using the classical Debye model, which indicates that the heat transport is purely phononic. Moreover, the low-T κc(H) isotherms with H || c display a field-independent behavior. These results indicate that there is no contribution of magnetic excitations to the thermal conductivity in Ca3Co2O6, neither carrying heat nor scattering phonons, which can be attributed to the Ising-like spin anisotropy.

  13. Photoluminescence and thermoluminescence characterization of Eu3+- and Dy3+ -activated Ca3(PO4)2 phosphor

    International Nuclear Information System (INIS)

    Nagpure, I.M.; Saha, Subhajit; Dhoble, S.J.

    2009-01-01

    Rare-earth-doped polycrystalline Ca 3 (PO 4 ) 2 :Eu, Ca 3 (PO 4 ) 2 :Dy and Ca 3 (PO 4 ) 2 :Eu,Dy phosphors prepared by a modified solid-state synthesis has been studied for its X-ray diffraction, thermoluminescence (TL) and photoluminescence (PL) characteristics. The PL emission spectra of the phosphor suggest the presence of Eu 3+ ion in Ca 3 (PO 4 ) 2 :Eu and Dy 3+ ion in Ca 3 (PO 4 ) 2 :Dy lattice sites. The TL glow curve of the Ca 3 (PO 4 ) 2 :Eu compounds has a simple structure with a prominent peak at 228 deg. C, while Ca 3 (PO 4 ) 2 :Dy peaking at 146 and 230 deg. C. TL sensitivity of phosphors are compared with CaSO 4 : Dy and found 1.52 and 1.20 times less in Ca 3 (PO 4 ) 2 :Eu and Ca 3 (PO 4 ) 2 :Dy phosphors, respectively. The Ca 3 (PO 4 ) 2 :Eu,Dy phosphors shows switching behavior under two different excitation wavelengths and enhancement in PL intensity of Dy 3+ ions were reported. The paper discusses the photoluminescence and thermoluminescence behavior of Eu 3+ and Dy 3+ ion in Ca 3 (PO 4 ) 2 hosts, it may be applicable to solid-state lighting as well as thermoluminescence dosimetry applications.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Characterization, scaling, and partial representation of diffuse and discrete input junctions to CA3 hippocampus.

    Science.gov (United States)

    Ascarrunz, F G; Kisley, M A; Flach, K A; Hamilton, R W; MacGregor, R J

    1995-07-01

    This paper applies a general mathematical system for characterizing and scaling functional connectivity and information flow across the diffuse (EC) and discrete (DG) input junctions to the CA3 hippocampus. Both gross connectivity and coordinated multiunit informational firing patterns are quantitatively characterized in terms of 32 defining parameters interrelated by 17 equations, and then scaled down according to rules for uniformly proportional scaling and for partial representation. The diffuse EC-CA3 junction is shown to be uniformly scalable with realistic representation of both essential spatiotemporal cooperativity and coordinated firing patterns down to populations of a few hundred neurons. Scaling of the discrete DG-CA3 junction can be effected with a two-step process, which necessarily deviates from uniform proportionality but nonetheless produces a valuable and readily interpretable reduced model, also utilizing a few hundred neurons in the receiving population. Partial representation produces a reduced model of only a portion of the full network where each model neuron corresponds directly to a biological neuron. The mathematical analysis illustrated here shows that although omissions and distortions are inescapable in such an application, satisfactorily complete and accurate models the size of pattern modules are possible. Finally, the mathematical characterization of these junctions generates a theory which sees the DG as a definer of the fine structure of embedded traces in the hippocampus and entire coordinated patterns of sequences of 14-cell links in CA3 as triggered by the firing of sequences of individual neurons in DG.

  19. Electronic Structure and Thermoelectric Properties of Ca3 Co4O9

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The relation among electronic structure, chemical bond and thermoelectric property of Ca3 Co4 O9 was studied using density function and discrete variation method (DFT-DVM).The gap between the highest valence band (HVB) and the lowest conduction band (LCB) shows a semiconducting property.Ca3 Co4 O9 colsists of CoO2 and Ca2 CoO3 two layers.The HVB and LCB near Fermi level are only mainly from O(2) 2p and Co(2) 3d in Ca2 CoO3 layer. Therefore, the semiconducting or thermoelectric property of Ca3 Co4 O9 should be mainly from Ca2 CoO3 layer, but it seems to have no direct relation to the CoO2 layer,which is consistent with that binary oxides hardly have a thermoelectric property, but trinary oxide compounds have quite a good thermoelectric property.The covalent and ionic bonds of Ca2 CoO3 layer are both weaker than those of CoO2 layer.Ca plays the role of connections between CoO2 and Ca2 CoO3 layers in Ca3 Co4 O9, decrease the ionic and covalent bond strength, and improve the thermoelectric property.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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.

  3. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  4. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

    Science.gov (United States)

    Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

    2017-05-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  5. Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission.

    Science.gov (United States)

    Lalic, Tatjana; Pettingill, Philippa; Vincent, Angela; Capogna, Marco

    2011-01-01

    Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well-recognized form of LE is associated with voltage-gated potassium channel complex antibodies (VGKC-Abs) in the patients' sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC-Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy-fiber (MF)-CA3 pyramidal cell synapses. We compared the effects of LE and healthy control IgG by whole-cell patch-clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices. We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF-evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF-CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α-dendrotoxin (120 nm), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG-mediated effects. This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  6. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

  7. 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.

  8. NMDA-dependent phase synchronization between septal and temporal CA3 hippocampal networks.

    Science.gov (United States)

    Gu, Ning; Jackson, Jesse; Goutagny, Romain; Lowe, Germaine; Manseau, Frédéric; Williams, Sylvain

    2013-05-08

    Increasing evidence suggests that synchronization between brain regions is essential for information exchange and memory processes. However, it remains incompletely known which synaptic mechanisms contribute to the process of synchronization. Here, we investigated whether NMDA receptor-mediated synaptic plasticity was an important player in synchronization between septal and temporal CA3 areas of the rat hippocampus. We found that both the septal and temporal CA3 regions intrinsically generate weakly synchronized δ frequency oscillations in the complete hippocampus in vitro. Septal and temporal oscillators differed in frequency, power, and rhythmicity, but both required GABAA and AMPA receptors. NMDA receptor activation, and most particularly the NR2B subunit, contributed considerably more to rhythm generation at the temporal than the septal region. Brief activation of NMDA receptors by application of extracellular calcium dramatically potentiated the septal-temporal coherence for long durations (>40 min), an effect blocked by the NMDA antagonist AP-5. This long-lasting NMDA-receptor-dependent increase in coherence was also associated with an elevated phase locking of spikes locally and across regions. Changes in coherence between oscillators were associated with increases in phase locking between oscillators independent of oscillator amplitude. Finally, although the septal CA3 rhythm preceded the oscillations in temporal regions in control conditions, this was reversed during the NMDA-dependent enhancement in coherence, suggesting that NMDA receptor activation can change the direction of information flow along the septotemporal CA3 axis. These data demonstrate that plastic changes in communication between septal and temporal hippocampal regions can arise from the NMDA-dependent phase locking of neural oscillators.

  9. Hippocampal CA3 transcriptome signature correlates with initial precipitating injury in refractory mesial temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Silvia Y Bando

    Full Text Available BACKGROUND: Prolonged febrile seizures constitute an initial precipitating injury (IPI commonly associated with refractory mesial temporal lobe epilepsy (RMTLE. In order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS or without (NFS febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations. METHODOLOGY/PRINCIPAL FINDINGS: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs. Co-expression network analysis showed that: i CA3 transcriptomic profiles differ according to the IPI; ii FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi. CONCLUSIONS/SIGNIFICANCE: CA3 transcriptional signatures and dentate gyrus morphology fairly

  10. Hydrothermal synthesis of Ca3Bi8O15 rods and their visible light photocatalytic properties

    International Nuclear Information System (INIS)

    Li, Wenjuan; Kong, Desheng; Cui, Xiaoli; Du, Dandan; Yan, Tingjiang; You, Jinmao

    2014-01-01

    Graphical abstract: The novel Ca 3 Bi 8 O 15 rods can utilize the sunlight efficiently with the small band-gap. Using methyl orange (MO) as a model organic pollutant, the photocatalysts exhibited good photocatalytic activity, with the photodegradation conversion ratio of MO being up to 90% after 2 h of visible light (420 nm < λ < 800 nm) irradiation. - Highlights: • Ca 3 Bi 8 O 15 rods were synthesized by a hydrothermal method. • They can utilize the sunlight efficiently with the small band-gap. • They showed good photocatalytic activities in the degradation of MO, RhB and 4-CP. • The conversion ratio of MO was up to 90% after 2 h of visible light irradiation. - Abstract: High efficient visible light Ca 3 Bi 8 O 15 photocatalysts were synthesized by a hydrothermal method. Characterized by X-ray diffractometer, transmission electron microscopy, and the UV–vis diffuse reflectance spectroscopy, the results showed that the novel Ca 3 Bi 8 O 15 rods can utilize the sunlight efficiently with the small band-gap. Using methyl orange (MO) as a model organic pollutant, the photocatalysts exhibited good photocatalytic activity, with the photodegradation conversion ratio of MO being up to 90% after 2 h of visible light (420 nm < λ < 800 nm) irradiation. Furthermore, they also showed good photocatalytic activities in the degradation of rhodamine B and p-chlorophenol. Through the investigation of the degraded mechanism, the main active species played important roles in the degradation process were holes, O 2 · − and ·OH

  11. Transport and NMR characteristics of the skutterudite-related compound Ca3Rh4Sn13

    Science.gov (United States)

    Tseng, C. W.; Kuo, C. N.; Li, B. S.; Wang, L. M.; Gippius, A. A.; Kuo, Y. K.; Lue, C. S.

    2018-02-01

    We report the electronic properties of the Yb3Rh4Sn13-type single crystalline Ca3Rh4Sn13 by means of the electrical resistivity, Hall coefficient, Seebeck coefficient, thermal conductivity, as well as 119Sn nuclear magnetic resonance (NMR) measurements. The negative sign of the Hall coefficient and Seebeck coefficient at low temperatures suggests that the n-type carriers dominate the electrical transport in Ca3Rh4Sn13, in contrast to the observations in Sr3Rh4Sn13 which has a p-type conduction. Such a finding indicates a significant difference in the electronic features between these two stannides. Furthermore, we analyzed the temperature-dependent 119Sn NMR spin-lattice relaxation rate for Ca3Rh4Sn13, (Sr0.7Ca0.3)3Rh4Sn13, and Sr3Rh4Sn13 to examine the change of the electronic Fermi-level density of states (DOS) in (Sr1-xCax)3Rh4Sn13. It indicates that the Sn 5s partial Fermi-level DOS enhances with increasing the Ca content, being consistent with the trend of the superconducting temperature. Since the total Fermi-level DOS usually obeys the same trend of the partial Fermi-level DOS, the NMR analysis provides microscopic evidence for the correlation between the electronic DOS and superconductivity of the (Sr1-xCax)3Rh4Sn13 system.

  12. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Liyuan Zhang

    2017-07-01

    Full Text Available In temporal lobe epilepsy (TLE, the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin–Huxley (HH type neurons and Pinsky–Rinzel (PR type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR, we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  13. Heteroassociative storage of hippocampal pattern sequences in the CA3 subregion

    Directory of Open Access Journals (Sweden)

    Raphael Y. de Camargo

    2018-01-01

    Full Text Available Background Recent research suggests that the CA3 subregion of the hippocampus has properties of both autoassociative network, due to its ability to complete partial cues, tolerate noise, and store associations between memories, and heteroassociative one, due to its ability to store and retrieve sequences of patterns. Although there are several computational models of the CA3 as an autoassociative network, more detailed evaluations of its heteroassociative properties are missing. Methods We developed a model of the CA3 subregion containing 10,000 integrate-and-fire neurons with both recurrent excitatory and inhibitory connections, and which exhibits coupled oscillations in the gamma and theta ranges. We stored thousands of pattern sequences using a heteroassociative learning rule with competitive synaptic scaling. Results We showed that a purely heteroassociative network model can (i retrieve pattern sequences from partial cues with external noise and incomplete connectivity, (ii achieve homeostasis regarding the number of connections per neuron when many patterns are stored when using synaptic scaling, (iii continuously update the set of retrievable patterns, guaranteeing that the last stored patterns can be retrieved and older ones can be forgotten. Discussion Heteroassociative networks with synaptic scaling rules seem sufficient to achieve many desirable features regarding connectivity homeostasis, pattern sequence retrieval, noise tolerance and updating of the set of retrievable patterns.

  14. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy.

    Science.gov (United States)

    Zhang, Liyuan; Fan, Denggui; Wang, Qingyun

    2017-01-01

    In temporal lobe epilepsy (TLE), the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG) region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR), we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  15. The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region☆

    Science.gov (United States)

    Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

    2012-01-01

    In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. PMID:25657670

  16. Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo

    Science.gov (United States)

    Tukker, John J; Klausberger, Thomas; Somogyi, Peter

    2015-01-01

    Hippocampal sharp waves are population discharges initiated by an unknown mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate action potential generation through GABAergic synapses on the axon initial segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving rats stopped firing during sharp waves, when pyramidal cells fire most. AACs fired strongly and rhythmically around the peak of theta oscillations, when pyramidal cells fire at low probability. Distinguishing AACs from other parvalbumin-expressing interneurons by their lack of detectable SATB1 transcription factor immunoreactivity, we discovered a somatic GABAergic input originating from the medial septum that preferentially targets AACs. We recorded septo-hippocampal GABAergic cells that were activated during hippocampal sharp waves and projected to CA3. We hypothesize that inhibition of AACs, and the resulting subcellular redistribution of inhibition from the axon initial segment to other pyramidal cell domains, is a necessary condition for the emergence of sharp waves promoting memory consolidation. PMID:24141313

  17. 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.

  18. 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.

  19. 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.

  20. Ischemic damage in hippocampal CA1 is dependent on glutamate release and intact innervation from CA3

    DEFF Research Database (Denmark)

    Benveniste, H; Jørgensen, M B; Sandberg, M

    1989-01-01

    The removal of glutamatergic afferents to CA1 by destruction of the CA3 region is known to protect CA1 pyramidal cells against 10 min of transient global ischemia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CA...

  1. 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.

  2. 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

  3. Interrelation between domain structures and polarization switching in hybrid improper ferroelectric Ca3(Mn,Ti)2O7

    Science.gov (United States)

    Gao, Bin; Huang, Fei-Ting; Wang, Yazhong; Kim, Jae-Wook; Wang, Lihai; Lim, Seong-Joon; Cheong, Sang-Wook

    2017-05-01

    Ca3Mn2O7 and Ca3Ti2O7 have been proposed as the prototypical hybrid improper ferroelectrics (HIFs), and a significant magnetoelectric (ME) coupling in magnetic Ca3Mn2O7 is, in fact, reported theoretically and experimentally. Although the switchability of polarization is confirmed in Ca3Ti2O7 and other non-magnetic HIFs, there is no report of switchable polarization in the isostructural Ca3Mn2O7. We constructed the phase diagram of Ca3Mn2-xTixO7 through our systematic study of a series of single crystalline Ca3Mn2-xTixO7 (x = 0, 0.1, 1, 1.5, and 2). Using transmission electron microscopy, we have unveiled the unique domain structure of Ca3Mn2O7: the high-density 90° stacking of a- and b-domains along the c-axis due to the phase transition through an intermediate Acca phase and the in-plane irregular wavy ferroelastic twin domains. The interrelation between domain structures and physical properties is unprecedented: the stacking along the c-axis prevents the switching of polarization and causes the irregular in-plane ferroelastic domain pattern. In addition, we have determined the magnetic phase diagram and found complex magnetism of Ca3Mn2O7 with isotropic canted moments. These results lead to negligible observable ME coupling in Ca3Mn2O7 and guide us to explore multiferroics with large ME coupling.

  4. 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.

  5. 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

  6. 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.

  7. High-temperature resistivity and thermoelectric properties of coupled substituted Ca3Co2O6

    Directory of Open Access Journals (Sweden)

    Meenakshisundaram Senthilkumar and Rajagopalan Vijayaraghavan

    2009-01-01

    Full Text Available Polycrystalline samples of Ca3−xNaxCo2−xMnxO6 (x=0.0–0.5 have been prepared by the sol-gel cum combustion method using sucrose in order to investigate the effects of the coupled substitution of Na and Mn on Ca and Co sites on the transport properties of Ca3Co2O6(Co326. The products were characterized by Fourier transform infrared spectroscopy, powder x-ray diffraction (XRD, thermogravimetry (TGA, differential thermal analysis and scanning electron microscopy. XRD patterns reveal the formation of single-phase products up to x=0.5. Coupled substitution increases the solubility of both Na and Mn on Ca and Co sites, respectively, in contrast to the limited solubility of Na and Mn (x=0.2 when separately substituted. TGA confirms the formation of the Ca3Co2O6 phase at temperatures ~720 °C. The grain size of the parent and substituted products is in the range 150–250 nm. Electrical resistivity and Seebeck coefficient were measured in the temperature range 300–800 K. Resistivity shows semiconducting behavior for all the compositions, particularly in the low-temperature regime. The Seebeck coefficient increases with temperature throughout the measured temperature range for all compositions. The maximum Seebeck coefficient (200 μV K−1 is observed for x=0.5 at 825 K, and this composition may be optimal for high-temperature thermoelectric applications.

  8. Regulation of phenylacetic acid uptake is sigma54 dependent in Pseudomonas putida CA-3.

    LENUS (Irish Health Repository)

    O' Leary, Niall D

    2011-10-13

    Abstract Background Styrene is a toxic and potentially carcinogenic alkenylbenzene used extensively in the polymer processing industry. Significant quantities of contaminated liquid waste are generated annually as a consequence. However, styrene is not a true xenobiotic and microbial pathways for its aerobic assimilation, via an intermediate, phenylacetic acid, have been identified in a diverse range of environmental isolates. The potential for microbial bioremediation of styrene waste has received considerable research attention over the last number of years. As a result the structure, organisation and encoded function of the genes responsible for styrene and phenylacetic acid sensing, uptake and catabolism have been elucidated. However, a limited understanding persists in relation to host specific regulatory molecules which may impart additional control over these pathways. In this study the styrene degrader Pseudomonas putida CA-3 was subjected to random mini-Tn5 mutagenesis and mutants screened for altered styrene\\/phenylacetic acid utilisation profiles potentially linked to non-catabolon encoded regulatory influences. Results One mutant, D7, capable of growth on styrene, but not on phenylacetic acid, harboured a Tn5 insertion in the rpoN gene encoding σ54. Complementation of the D7 mutant with the wild type rpoN gene restored the ability of this strain to utilise phenylacetic acid as a sole carbon source. Subsequent RT-PCR analyses revealed that a phenylacetate permease, PaaL, was expressed in wild type P. putida CA-3 cells utilising styrene or phenylacetic acid, but could not be detected in the disrupted D7 mutant. Expression of plasmid borne paaL in mutant D7 was found to fully restore the phenylacetic acid utilisation capacity of the strain to wild type levels. Bioinformatic analysis of the paaL promoter from P. putida CA-3 revealed two σ54 consensus binding sites in a non-archetypal configuration, with the transcriptional start site being resolved by

  9. High-pressure crystal growth and electromagnetic properties of 5d double-perovskite Ca3OsO6

    International Nuclear Information System (INIS)

    Feng, Hai Luke; Shi, Youguo; Guo, Yanfeng; Li, Jun; Sato, Akira; Sun, Ying; Wang, Xia; Yu, Shan; Sathish, Clastin I.; Yamaura, Kazunari

    2013-01-01

    Single crystals of the osmium-containing compound Ca 3 OsO 6 have been successfully grown under high-pressure conditions, for the first time. The crystal structure of Ca 3 OsO 6 were characterized as an ordered double-perovskite structure of space group P2 1 /n with the Ca and Os atoms being fully ordered at the perovskite B-site. The electromagnetic analysis shows that the crystal exhibits a semiconductor-like behavior below 300 K and undergoes an antiferromagnetic transition at 50 K. - Graphical Abstract: Schematic image of crystal structure of Ca 3 OsO 6 as determined by X-ray diffraction, where the gray and black octahedrons are occupied by Ca and Os, respectively. Top inset reveals an optic image of a typical Ca 3 OsO 6 single crystal. Highlights: ► Single crystals of Ca 3 OsO 6 have been successfully grown under high-pressure. ► Ca 3 OsO 6 crystalizes into an ordered double-perovskite structure. ► The Ca 3 OsO 6 undergoes an antiferromagnetic transition at 50 K

  10. Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

    Science.gov (United States)

    Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

    2016-01-01

    Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. Electrolytic lesions of dorsal CA3 impair episodic-like memory in rats.

    Science.gov (United States)

    Li, Jay-Shake; Chao, Yuen-Shin

    2008-02-01

    Episodic memory is the ability to recollect one's past experiences occurring in an unique spatial and temporal context. In non-human animals, it is expressed in the ability to combine "what", "where" and "when" factors to form an integrated memory system. During the search for its neural substrates, the hippocampus has attracted a lot of attentions. Yet, it is not yet possible to induce a pure episodic-like memory deficit in animal studies without being confounded by impairments in the spatial cognition. Here, we present a lesion study evidencing direct links between the hippocampus CA3 region and the episodic-like memory in rats. In a spontaneous object exploration task, lesioned rats showed no interaction between the temporal and spatial elements in their memory associated with the objects. In separate tests carried out subsequently, the same animals still expressed abilities to process spatial, temporal, and object recognition memory. In conclusions, our results support the idea that the hippocampus CA3 has a particular status in the neural mechanism of the episodic-like memory system. It is responsible for combining information from different modules of cognitive processes.

  16. Optimal recall from bounded metaplastic synapses: predicting functional adaptations in hippocampal area CA3.

    Directory of Open Access Journals (Sweden)

    Cristina Savin

    2014-02-01

    Full Text Available A venerable history of classical work on autoassociative memory has significantly shaped our understanding of several features of the hippocampus, and most prominently of its CA3 area, in relation to memory storage and retrieval. However, existing theories of hippocampal memory processing ignore a key biological constraint affecting memory storage in neural circuits: the bounded dynamical range of synapses. Recent treatments based on the notion of metaplasticity provide a powerful model for individual bounded synapses; however, their implications for the ability of the hippocampus to retrieve memories well and the dynamics of neurons associated with that retrieval are both unknown. Here, we develop a theoretical framework for memory storage and recall with bounded synapses. We formulate the recall of a previously stored pattern from a noisy recall cue and limited-capacity (and therefore lossy synapses as a probabilistic inference problem, and derive neural dynamics that implement approximate inference algorithms to solve this problem efficiently. In particular, for binary synapses with metaplastic states, we demonstrate for the first time that memories can be efficiently read out with biologically plausible network dynamics that are completely constrained by the synaptic plasticity rule, and the statistics of the stored patterns and of the recall cue. Our theory organises into a coherent framework a wide range of existing data about the regulation of excitability, feedback inhibition, and network oscillations in area CA3, and makes novel and directly testable predictions that can guide future experiments.

  17. Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

    Directory of Open Access Journals (Sweden)

    Roman A Sandler

    2017-07-01

    Full Text Available Much of the research on cannabinoids (CBs has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC, the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

  18. 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.

  19. Dendrite Injury Triggers DLK-Independent Regeneration

    Directory of Open Access Journals (Sweden)

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  20. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

    Science.gov (United States)

    Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

    2016-10-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition

  1. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory

    Science.gov (United States)

    Hooper, Andrew; Maguire, Jamie

    2016-01-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAAR) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells; whereas, there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAAR δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAAR δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAAR δ subunit-mediated tonic inhibition in

  2. Disruption of hippocampal CA3 network: effects on episodic-like memory processing in C57BL/6J mice.

    Science.gov (United States)

    Daumas, Stéphanie; Halley, Hélène; Lassalle, Jean-Michel

    2004-07-01

    Lesion studies have demonstrated the prominent role of the hippocampus in spatial and contextual learning. To better understand how contextual information is processed in the CA3 region during learning, we focused on the CA3 autoassociative network hypothesis. We took advantage of a particularity of the mossy fibre (MF) synapses, i.e. their high zinc concentration, to reversibly disrupt the afferent MF pathway by microinfusions of an intracellular (DEDTC) or an extracellular (CaEDTA) zinc chelator into the CA3 area of the dorsal hippocampus of mice. Disruption of the CA3 network significantly impaired the acquisition and the consolidation of contextual fear conditioning, whereas contextual retrieval was unaffected. These results also suggest a heterogeneity between the cognitive processes underlying spatial and contextual memory that might be linked to the specific involvement of free zinc in contextual information processing.

  3. 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.

  4. Enhanced electrochemical performance of the solid oxide fuel cell cathode using Ca3Co4O9+δ

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Van Nong, Ngo

    2011-01-01

    This paper reports on the electrochemical performance of an SOFC cathode for potential use in intermediate-temperature solid oxide fuel cells (IT-SOFCs) using the oxygen non-stoichiometric misfit-layered cobaltite Ca3Co4O9+δ or composites of Ca3Co4O9+δ with Ce0.9Gd0.1O1.95 (CGO/Ca3Co4O9+δ......). Electrochemical impedance spectroscopy revealed that symmetric cells with an electrode of pure Ca3Co4O9+δ exhibit a cathode polarization resistance (Rp) of 12.4 Ω cm2, at 600 °C in air. Strikingly, Rp of the composite CGO/Ca3Co4O9+δ with 50 vol.% CGO was reduced by a factor of 19 (i.e. Rp = 0.64 Ω cm2......), the lowest value reported so far for the Ca3Co4O9 family of compounds. These findings together with the reported thermal expansion coefficient, good compatibility with CGO and chemical durability of this material suggest that it is a promising candidate cathode for IT-SOFCs....

  5. Thermoelectric Properties of the Chemically Doped Ca3Co4O9 System: A Structural Perspective

    Science.gov (United States)

    Wu, Tao; Tyson, Trevor; Wang, Hsin; Li, Qiang

    2010-03-01

    Cu doped and Y doped [Ca2CoO3][CoO2]1.61 (referred to as Ca3Co4O9) were prepared by solid state reaction. Temperature dependent thermoelectric properties, resistivity (ρ), Seeback coefficient (S) and thermal conductivity (κ), were measured. As seen before, it is found that doping by Cu and Y significantly enhances the thermoelectric properties. In order to understand the origin of these changes in properties in terms of the atomic structure, synchrotron x-ray diffraction and x-ray absorption spectroscopy were applied to probe the change in the average structure and the location of the dopants. The details of the location and coordination of Co and Y in the host lattice and the effect on the figure of merit are discussed. This work is supported by DOE Grant DE-FG02-07ER46402.

  6. Scintillation characteristics of Tm3+ in Ca3(BO3)2 crystals

    International Nuclear Information System (INIS)

    Fujimoto, Yutaka; Yanagida, Takayuki; Yokota, Yuui; Kawaguchi, Noriaki; Fukuda, Kentaro; Totsuka, Daisuke; Watanabe, Kenichi; Yamazaki, Atsushi; Yoshikawa, Akira

    2011-01-01

    Basic optical properties and radiation responses of undoped, Tm 3+ 1.0% and 2.0% activated Ca 3 (BO 3 ) 2 (CBO) crystalline scintillator prepared by the micro-pulling down (μ-PD) method are reported. Tm 3+ : CBO crystals showed three weak absorption bands around 190, 260 and 350 nm, owing to the Tm 3+ 4f–4f transition. Strong blue luminescence peaks at 360 and 460 nm which are ascribed to the 1 D 2 – 3 H 6 and 1 D 2 – 3 F 4 transitions of Tm 3+ respectively were observed under 241 Am 5.5 MeV α-ray excitation. The scintillation light yield of 2.0% Tm 3+ -doped CBO crystal was evaluated to be about 250 ph/n from the 252 Cf excited pulse height spectrum.

  7. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao; Rose, Marie E. [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States); Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurosurgery, University of Pittsburgh, PA 15216 (United States); Department of Critical Care Medicine, University of Pittsburgh, PA 15216 (United States); Graham, Steven H., E-mail: Steven.Graham@va.gov [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States)

    2016-04-15

    Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

  8. THE QUADRUPLE PRE-MAIN-SEQUENCE SYSTEM LkCa 3: IMPLICATIONS FOR STELLAR EVOLUTION MODELS

    International Nuclear Information System (INIS)

    Torres, Guillermo; Latham, David W.; Ruíz-Rodríguez, Dary; Prato, L.; Wasserman, Lawrence H.; Badenas, Mariona; Schaefer, G. H.; Mathieu, Robert D.

    2013-01-01

    We report the discovery that the pre-main-sequence (PMS) object LkCa 3 in the Taurus-Auriga star-forming region is a hierarchical quadruple system of M stars. It was previously known to be a close (∼0.''5) visual pair, with one component being a moderately eccentric 12.94 day single-lined spectroscopic binary. A re-analysis of archival optical spectra complemented by new near-infrared (NIR) spectroscopy shows both visual components to be double lined; the second one has a period of 4.06 days and a circular orbit. In addition to the orbital elements, we determine optical and NIR flux ratios, effective temperatures, and projected rotational velocities for all four stars. Using existing photometric monitoring observations of the system that had previously revealed the rotational period of the primary in the longer-period binary, we also detect the rotational signal of the primary in the 4.06 day binary, which is synchronized with the orbital motion. With only the assumption of coevality, a comparison of all of these constraints with current stellar evolution models from the Dartmouth series points to an age of 1.4 Myr and a distance of 133 pc, consistent with previous estimates for the region and suggesting that the system is on the near side of the Taurus complex. Similar comparisons of the properties of LkCa 3 and the well-known quadruple PMS system GG Tau with the widely used models from the Lyon series for a mixing length parameter of α ML = 1.0 strongly favor the Dartmouth models

  9. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

    International Nuclear Information System (INIS)

    Liu, Hao; Rose, Marie E.; Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward; Graham, Steven H.

    2016-01-01

    Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

  10. Age-related Changes in Lateral Entorhinal and CA3 Neuron Allocation Predict Poor Performance on Object Discrimination

    Directory of Open Access Journals (Sweden)

    Andrew P. Maurer

    2017-06-01

    Full Text Available Age-related memory deficits correlate with dysfunction in the CA3 subregion of the hippocampus, which includes both hyperactivity and overly rigid activity patterns. While changes in intrinsic membrane currents and interneuron alterations are involved in this process, it is not known whether alterations in afferent input to CA3 also contribute. Neurons in layer II of the lateral entorhinal cortex (LEC project directly to CA3 through the perforant path, but no data are available regarding the effects of advanced age on LEC activity and whether these activity patterns update in response to environmental change. Furthermore, it is not known the extent to which age-related deficits in sensory discrimination relate to the inability of aged CA3 neurons to update in response to new environments. Young and aged rats were pre-characterized on a LEGO© object discrimination task, comparable to behavioral tests in humans in which CA3 hyperactivity has been linked to impairments. The cellular compartment analysis of temporal activity with fluorescence in situ hybridization for the immediate-early gene Arc was then used to identify the principal cell populations that were active during two distinct epochs of random foraging in different environments. This approach enabled the extent to which rats could discriminate two similar objects to be related to the ability of CA3 neurons to update across different environments. In both young and aged rats, there were animals that performed poorly on the LEGO object discrimination task. In the aged rats only, however, the poor performers had a higher percent of CA3 neurons that were active during random foraging in a novel environment, but this is not related to the ability of CA3 neurons to remap when the environment changed. Afferent neurons to CA3 in LEC, as identified with the retrograde tracer choleratoxin B (CTB, also showed a higher percentage of cells that were positive for Arc mRNA in aged poor performing rats

  11. Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

    Science.gov (United States)

    Touyarot, K.; Sandi, C.

    2002-01-01

    Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

  12. 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

  13. [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.

  14. INFLUENCE OF ELECTROACUPUNCTURE ON THE ULTRASTRUCTURE OF CA3 REGION OF THE HIPPOCAMPUS IN VD RATS

    Institute of Scientific and Technical Information of China (English)

    YAN Bing; XU Neng-gui; HE Li-lei; TANG Chun-zhi; SHAO Ying

    2006-01-01

    Objective: To observe the effect of electroacupuncture (EA) on learning and memory abilities and ultrastructure of synapses in CA3 region of the hippocampus in vascular dementia (VD) rats. Methods: A total of 32 SD rats were randomized into control (sham-operation, n = 7), model (n = 7), EA (n = 9) and medication (n=9) groups. VD model was established by occlusion of the bilateral vertebral arteries (electrocoagulation) and bilateral common carotid arteries (occlusion for 5 min and reperfusion for 10 min, repeated the procedure for 3 times to induce global ischemia). EA (150 Hz, 1 mA) was applied to "Baihui"(百会GV 20), "Geshu"(膈俞 BL 17), "Pishu"(脾俞 BL 20) and "Shenshu"(肾俞 BL 23) for 20 min, once daily and continuously for 15 days. In medication group, the rats were fed with Nimotong (12 mg/kg), once daily and continuously for 15 days. Morris water maze method was used to test the animals' learning and memory abilities (latencies to find the hidden platform determined by place navigation trials, and latencies to cross on the location of the removed platform determined by spatial probe trials) after the treatment. Ultrastructural changes (numerical density, NA,surface density, Sv and volume density, Vv) of Gray type 1 synapses in CA3 region of the hippocampus were observed by using transmission electronic microscope and automatic image analysis system. Results: 1 ) Place navigation test showed that in comparison with control group, the average escape latency of VD group was significantly longer (P<0.01), while in comparison with VD group, the latencies of both EA and medication groups decreased significantly ( P<0.01 ). No significant difference was found between EA and medication groups in the escape latency (P>0.05). 2) Spatial probe-test displayed that in comparison with control group, the times which the animals crossed the target platform in VD group decreased significantly (P<0.01), while compared with VD group, those of both EA and

  15. Phase transition and multicolor luminescence of Eu2+/Mn2+-activated Ca3(PO4)2 phosphors

    International Nuclear Information System (INIS)

    Li, Kai; Chen, Daqin; Xu, Ju; Zhang, Rui; Yu, Yunlong; Wang, Yuansheng

    2014-01-01

    Graphical abstract: We have synthesized Eu 2+ doped and Eu 2+ /Mn 2+ co-doped Ca 3 (PO 4 ) 2 phosphors. The emitting color varies from blue to green with increasing of Eu 2+ content for the Eu 2+ -doped phosphor, and the quantum yield of the 0.05Eu 2+ : Ca 2.95 (PO 4 ) 2 sample reaches 56.7%. Interestingly, Mn 2+ co-doping into Eu 2+ : Ca 3 (PO 4 ) 2 leads to its phase transition from orthorhombic to rhombohedral, and subsequently generates tunable multi-color luminescence from green to red via Eu 2+ → Mn 2+ energy transfer. - Highlights: • A series of novel Eu 2+ : Ca 3 (PO 4 ) 2 phosphors were successfully synthesized. • Phase transition of Ca 3 (PO 4 ) 2 from orthorhombic to rhombohedral occurred when Mn 2+ ions were doped. • The phosphors exhibited tunable multi-color luminescence. • The quantum yield of 0.05Eu 2+ : Ca 2.95 (PO 4 ) 2 phosphor can reach 56.7%. • The analyses of phosphors were carried out by many measurements. - Abstract: Intense blue-green-emitting Eu 2+ : Ca 3 (PO 4 ) 2 and tunable multicolor-emitting Eu 2+ /Mn 2+ : Ca 3 (PO 4 ) 2 phosphors are prepared via a solid-state reaction route. Eu 2+ -doped orthorhombic Ca 3 (PO 4 ) 2 phosphor exhibits a broad emission band in the wavelength range of 400–700 nm with a maximum quantum yield of 56.7%, and the emission peak red-shifts gradually from 479 to 520 nm with increase of Eu 2+ doping content. Broad excitation spectrum (250–420 nm) of Eu 2+ : Ca 3 (PO 4 ) 2 matches well with the near-ultraviolet LED chip, indicating its potential applications as tri-color phosphors in white LEDs. Interestingly, Mn 2+ co-doping into Eu 2+ : Ca 3 (PO 4 ) 2 leads to its phase transition from orthorhombic to rhombohedral, and subsequently generates tunable multi-color luminescence from green to red via Eu 2+ → Mn 2+ energy transfer, under 365 nm UV lamp excitation

  16. 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.

  17. 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.

  18. 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.

  19. Diminished Dentate Gyrus Filtering of Cortical Input Leads to Enhanced Area Ca3 Excitability after Mild Traumatic Brain Injury.

    Science.gov (United States)

    Folweiler, Kaitlin A; Samuel, Sandy; Metheny, Hannah E; Cohen, Akiva S

    2018-04-06

    Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to long-lasting episodic memory impairments. The encoding of episodic memories relies on spatial information processing within the hippocampus. As the primary entry point for spatial information into the hippocampus, the dentate gyrus is thought to function as a physiological gate, or filter, of afferent excitation before reaching downstream area Cornu Ammonis (CA3). Although injury has previously been shown to alter dentate gyrus network excitability, it is unknown whether mTBI affects dentate gyrus output to area CA3. In this study, we assessed hippocampal function, specifically the interaction between the dentate gyrus and CA3, using behavioral and electrophysiological techniques in ex vivo brain slices 1 week following mild lateral fluid percussion injury (LFPI). Behaviorally, LFPI mice were found to be impaired in an object-place recognition task, indicating that spatial information processing in the hippocampus is disrupted. Extracellular recordings and voltage-sensitive dye imaging demonstrated that perforant path activation leads to the aberrant spread of excitation from the dentate gyrus into area CA3 along the mossy fiber pathway. These results suggest that after mTBI, the dentate gyrus has a diminished capacity to regulate cortical input into the hippocampus, leading to increased CA3 network excitability. The loss of the dentate filtering efficacy reveals a potential mechanism by which hippocampal-dependent spatial information processing is disrupted, and may contribute to memory dysfunction after mTBI.

  20. Control of CA3 output by feedforward inhibition despite developmental changes in the excitation-inhibition balance.

    Science.gov (United States)

    Torborg, Christine L; Nakashiba, Toshiaki; Tonegawa, Susumu; McBain, Chris J

    2010-11-17

    In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.

  1. A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit.

    Science.gov (United States)

    Świetlik, D; Białowąs, J; Kusiak, A; Cichońska, D

    2018-01-01

    An experimental study of computational model of the CA3 region presents cog-nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = -0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210-220).

  2. Crystal structure and magnetic properties of the solid-solution phase Ca3Co2-v Sc v O6

    International Nuclear Information System (INIS)

    Hervoches, Charles H.; Fredenborg, Vivian Miksch; Kjekshus, Arne; Fjellvag, Helmer; Hauback, Bjorn C.

    2007-01-01

    The two crystallographically non-equivalent Co atoms of the quasi-one-dimensional crystal structure of Ca 3 Co 2 O 6 form chains with alternating, face-sharing polyhedra of Co2O 6 trigonal prisms and Co1O 6 octahedra. This compound forms a substitutional solid-solution phase with Sc, in which the Sc atoms enter the Co2 sublattice exclusively. The homogeneity range of Ca 3 Co 2- v Sc v O 6 (more specifically Ca 3 Co1Co2 1- v Sc v O 6 ) extends up to v∼0.55. The crystal structure belongs to space group R3-barc with lattice parameters (in hexagonal setting): 9.0846(3)≤a≤9.1300(2) A and 10.3885(4)≤c≤10.4677(4) A. The magnetic moment decreases rapidly with increasing amount of the non-magnetic Sc solute in the lattice. - Graphical abstract: The quasi-one-dimensional Ca 3 Co 2 O 6 phase forms a substitutional solid-solution system with Sc, in which the Sc atoms enter the Co2 sublattice exclusively. The homogeneity range of Ca 3 Co 2- v Sc v O 6 extends up to v∼0.55. The magnetic moment decreases rapidly with increasing amount of the non-magnetic Sc solute in the lattice

  3. Coding and decoding with dendrites.

    Science.gov (United States)

    Papoutsi, Athanasia; Kastellakis, George; Psarrou, Maria; Anastasakis, Stelios; Poirazi, Panayiota

    2014-02-01

    Since the discovery of complex, voltage dependent mechanisms in the dendrites of multiple neuron types, great effort has been devoted in search of a direct link between dendritic properties and specific neuronal functions. Over the last few years, new experimental techniques have allowed the visualization and probing of dendritic anatomy, plasticity and integrative schemes with unprecedented detail. This vast amount of information has caused a paradigm shift in the study of memory, one of the most important pursuits in Neuroscience, and calls for the development of novel theories and models that will unify the available data according to some basic principles. Traditional models of memory considered neural cells as the fundamental processing units in the brain. Recent studies however are proposing new theories in which memory is not only formed by modifying the synaptic connections between neurons, but also by modifications of intrinsic and anatomical dendritic properties as well as fine tuning of the wiring diagram. In this review paper we present previous studies along with recent findings from our group that support a key role of dendrites in information processing, including the encoding and decoding of new memories, both at the single cell and the network level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. 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.

  5. 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

  6. Synthesis of Ca_3CO_4O_9 via solid state reaction

    International Nuclear Information System (INIS)

    Melo, K.P.; Dutra, R.P.S.; Marques, K.A.; Junior, S.M.S.; Brasileiro, C.T.; Coutinho, S.V.C.R.; Souza, T.; Chagas, T.F.; Silva, R.M.; Macedo, D.A.

    2016-01-01

    Solid oxide fuel cells (SOFCs) stand out as the most promising today's energy conversion technologies. In the development of cathode materials for SOFC, calcium cobaltate (Ca3Co4O9, C349) appears as a potential alternative to traditional lanthanum manganites. In this work, C349 was prepared via solid state reaction of stoichiometric mixtures containing CaCO3 from mollusk shells, in natura (M1) and heat treated at 550 ° C (M2), and Co3O4 obtained by citrate method. The M1 and M2 mixtures were calcined at 800 (powder) and 900 ° C (tablets) for 12 h. The crystal structure and phase composition of the powder and the reaction products were studied by X-ray diffraction Rietveld refinement of the diffraction data. The results showed the formation of free C349 secondary stages, showing a good alternative to use waste from seafood shells as raw material for obtaining high-value ceramics.(author)

  7. Membrane voltage changes in passive dendritic trees: a tapering equivalent cylinder model.

    Science.gov (United States)

    Poznański, R R

    1988-01-01

    An exponentially tapering equivalent cylinder model is employed in order to approximate the loss of the dendritic trunk parameter observed from anatomical data on apical and basilar dendrites of CA1 and CA3 hippocampal pyramidal neurons. This model allows dendritic trees with a relative paucity of branching to be treated. In particular, terminal branches are not required to end at the same electrotonic distance. The Laplace transform method is used to obtain analytic expressions for the Green's function corresponding to an instantaneous pulse of current injected at a single point along a tapering equivalent cylinder with sealed ends. The time course of the voltage in response to an arbitrary input is computed using the Green's function in a convolution integral. Examples of current input considered are (1) an infinitesimally brief (Dirac delta function) pulse and (2) a step pulse. It is demonstrated that inputs located on a tapering equivalent cylinder are more effective at the soma than identically placed inputs on a nontapering equivalent cylinder. Asymptotic solutions are derived to enable the voltage response behaviour over both relatively short and long time periods to be analysed. Semilogarithmic plots of these solutions provide a basis for estimating the membrane time constant tau m from experimental transients. Transient voltage decrement from a clamped soma reveals that tapering tends to reduce the error associated with inadequate voltage clamping of the dendritic membrane. A formula is derived which shows that tapering tends to increase the estimate of the electrotonic length parameter L.

  8. Divergent Effects of Dendritic Cells on Pancreatitis

    Science.gov (United States)

    2015-09-01

    role of dendritic cells in pancreatitis. Dendritic cells are professional antigen presenting cells which initiate innate and adaptive immune... Lymphoid -tissue-specific homing of bone- marrow-derived dendritic cells . Blood. 113:6638–6647. http://dx.doi .org/10.1182/blood-2009-02-204321 Dapito...Award Number: W81XWH-12-1-0313 TITLE: Divergent Effects of Dendritic Cells on Pancreatitis PRINCIPAL INVESTIGATOR: Dr. George Miller

  9. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1.

    Science.gov (United States)

    Park, Kellie A; Ribic, Adema; Laage Gaupp, Fabian M; Coman, Daniel; Huang, Yuegao; Dulla, Chris G; Hyder, Fahmeed; Biederer, Thomas

    2016-07-13

    Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly

  10. Effects of Synthesis and Spark Plasma Sintering Conditions on the Thermoelectric Properties of Ca3Co4O9+δ

    DEFF Research Database (Denmark)

    Wu, NingYu; Holgate, Tim; Van Nong, Ngo

    2013-01-01

    Ca3Co4O9+δ samples were synthesized by solid-state (SS) and sol–gel (SG) reactions, followed by spark plasma sintering under different processing conditions. The synthesis process was optimized and the resulting materials characterized with respect to their microstructure, bulk density, and therm......Ca3Co4O9+δ samples were synthesized by solid-state (SS) and sol–gel (SG) reactions, followed by spark plasma sintering under different processing conditions. The synthesis process was optimized and the resulting materials characterized with respect to their microstructure, bulk density...

  11. High-pressure crystal growth and electromagnetic properties of 5d double-perovskite Ca3OsO6

    Science.gov (United States)

    Feng, Hai Luke; Shi, Youguo; Guo, Yanfeng; Li, Jun; Sato, Akira; Sun, Ying; Wang, Xia; Yu, Shan; Sathish, Clastin I.; Yamaura, Kazunari

    2013-05-01

    Single crystals of the osmium-containing compound Ca3OsO6 have been successfully grown under high-pressure conditions, for the first time. The crystal structure of Ca3OsO6 were characterized as an ordered double-perovskite structure of space group P21/n with the Ca and Os atoms being fully ordered at the perovskite B-site. The electromagnetic analysis shows that the crystal exhibits a semiconductor-like behavior below 300 K and undergoes an antiferromagnetic transition at 50 K.

  12. An inverse approach for elucidating dendritic function

    Directory of Open Access Journals (Sweden)

    Benjamin Torben-Nielsen

    2010-09-01

    Full Text Available We outline an inverse approach for investigating dendritic function-structure relationships by optimizing dendritic trees for a-priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a `hypothesis generator' in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a `function confirmation' by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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...

  19. 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...

  20. 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

  1. 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.)

  2. 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.)

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Neutrophils, dendritic cells and Toxoplasma.

    Science.gov (United States)

    Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

    2004-03-09

    Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

  9. Advanced dendritic web growth development

    Science.gov (United States)

    Hopkins, R. H.

    1985-01-01

    A program to develop the technology of the silicon dendritic web ribbon growth process is examined. The effort is being concentrated on the area rate and quality requirements necessary to meet the JPL/DOE goals for terrestrial PV applications. Closed loop web growth system development and stress reduction for high area rate growth is considered.

  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. Encoding, Consolidation, and Retrieval of Contextual Memory: Differential Involvement of Dorsal CA3 and CA1 Hippocampal Subregions

    Science.gov (United States)

    Daumas, Stephanie; Halley, Helene; Frances, Bernard; Lassalle, Jean-Michel

    2005-01-01

    Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting…

  13. Evidence of the Current Collector Effect: Study of the SOFC Cathode Material Ca3Co4O9+d

    NARCIS (Netherlands)

    Rolle, A.; Thoréton, V.; Rozier, P.; Capoen, E.; Mentré, O.; Boukamp, Bernard A.; Daviero-Minaud, S.

    2012-01-01

    In the study of the performance of solid oxide fuel cell (SOFC) electrodes, the possible influence of the applied current collector is often not mentioned or recognized. In this article, as part of an optimization study of the potentially attractive Ca3Co4O9+δ cathode material (Ca349), special

  14. Mechanical and thermal-expansion characteristics of Ca10(PO46(OH2-Ca3(PO42 composites

    Directory of Open Access Journals (Sweden)

    Ruseska G.

    2006-01-01

    Full Text Available Three types of composites consisting of Ca10(PO46(OH2 and Ca3(PO42 with composition: 75% (wt Ca10(PO46(OH2: 25%(wt Ca3(PO42; 50%(wt Ca10(PO46(OH2: 50%(wtCa3(PO42 and 25 %(wt Ca10(PO46(OH2: 75%(wt Ca3(PO42 were the subject of our investigation. Sintered compacts were in thermal equilibrium, which was proved by the absence of hysteresis effect of the dependence ΔL/L=f(T during heating /cooling in the temperature interval 20-1000-200C. Sintered compacts with the previously mentioned composition possess 26-50% higher values of the E-modulus, G-modulus and K-modulus indicating the presence of a synergism effect. Several proposed model equations for predicting the thermal expansion coefficient in dependence of the thermal and elastic properties of the constitutive phases and their volume fractions, given by: Turner, Kerner, Tummala and Friedberg, Thomas and Taya, were used for making correlations between mechanical and thermal-expansion characteristics of the Ca10(PO46(OH2 - Ca3(PO42 composites. Application of the previously mentioned model equations to all kinds of composites leads to the conclusion that the experimentally obtained results for the thermal expansion coefficient are in an excellent agreement with the theoretical calculated values on account of the volume fraction of each constitutive phase and with all applied model equations, with a coefficient of correlation from 98.16-99.86 %.

  15. A Change in Igneous Activity of the Jack Hills Zircon Sources ca. 3.9 Ga

    Science.gov (United States)

    Bell, E. A.; Harrison, T. M.

    2010-12-01

    New Ti-in-zircon crystallization temperature (Txlln) data for Jack Hills zircons reveal that the tight clustering of Hadean grains around a Txlln of 680°C, possibly indicative of felsic-to-intermediate minimum melting conditions, continues to ~3.92 Ga. Between 3.92-3.82 Ga the 680°C clustering ceases and most concordant grains cluster around an apparent Txlln of 610°C. A small group of zircons with higher Txlln (~750°C), present during the Hadean, is also observed during this period. After 3.82 Ga a Hadean-like distribution resumes for ~100 Ma. This large, concordant, low-Ti group at ~3.9 Ga is statistically distinct from the Hadean distribution and appears to be unique in the Jack Hills zircon record. The existence of coeval high- and low-Ti groups suggests that two distinct zircon-forming processes are distinguishable ~3.9 Ga, unlike during the Hadean. The significant numbers of zircons with apparent Txlln below 600°C may be suggestive of subsolidus formation, since igneous units with solidii below 600°C are relatively rare. The higher-Ti group is more consistent with an intermediate to mafic igneous origin but metamorphic overprinting or subsolidus formation at granulite grade cannot be ruled out by Txlln alone. A substantial proportion of the high-Ti group display oscillatory and disrupted oscillatory zoning in cathodoluminescence images, usually indicative of igneous origins and later metamorphism, respectively; most low-Ti grains are homogeneous. Several of each group display patchy zonation indicative of metamorphic overprinting. Although several grains with apparent Txlln >600°C display oscillatory zonation, the majority of the low-Ti group do not show textural evidence for igneous origins. We interpret these results to indicate the transition from a mechanism(s) that produced dominantly 680°C apparent zircon temperatures at ca. 3.9 Ga to include a new zircon-forming process in the sediment source(s), likely a protracted period of metamorphism

  16. Chronic Stress Reduces Nectin-1 mRNA Levels and Disrupts Dendritic Spine Plasticity in the Adult Mouse Perirhinal Cortex

    Directory of Open Access Journals (Sweden)

    Qian Gong

    2018-03-01

    Full Text Available In adulthood, chronic exposure to stressful experiences disrupts synaptic plasticity and cognitive function. Previous studies have shown that perirhinal cortex-dependent object recognition memory is impaired by chronic stress. However, the stress effects on molecular expression and structural plasticity in the perirhinal cortex remain unclear. In this study, we applied the chronic social defeat stress (CSDS paradigm and measured the mRNA levels of nectin-1, nectin-3 and neurexin-1, three synaptic cell adhesion molecules (CAMs implicated in the adverse stress effects, in the perirhinal cortex of wild-type (WT and conditional forebrain corticotropin-releasing hormone receptor 1 conditional knockout (CRHR1-CKO mice. Chronic stress reduced perirhinal nectin-1 mRNA levels in WT but not CRHR1-CKO mice. In conditional forebrain corticotropin-releasing hormone conditional overexpression (CRH-COE mice, perirhinal nectin-1 mRNA levels were also reduced, indicating that chronic stress modulates nectin-1 expression through the CRH-CRHR1 system. Moreover, chronic stress altered dendritic spine morphology in the main apical dendrites and reduced spine density in the oblique apical dendrites of perirhinal layer V pyramidal neurons. Our data suggest that chronic stress disrupts cell adhesion and dendritic spine plasticity in perirhinal neurons, which may contribute to stress-induced impairments of perirhinal cortex-dependent memory.

  17. Microtubule nucleation and organization in dendrites

    Science.gov (United States)

    Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

    2016-01-01

    ABSTRACT Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

  18. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. Spin texture of the surface state of three-dimensional Dirac material Ca3PbO

    Science.gov (United States)

    Kariyado, Toshikaze

    2015-04-01

    The bulk and surface electronic structures of a candidate three-dimensional Dirac material Ca3PbO and its family are discussed especially focusing on the spin texture on the surface states. We first explain the basic features of the bulk band structure of Ca3PbO, such as emergence of Dirac fermions near the Fermi energy, and compare it with the other known three-dimensional Dirac semimetals. Then, the surface bands and spin-texture on them are investigated in detail. It is shown that the surface bands exhibit strong momentum-spin locking, which may be useful in some application for spin manipulation, induced by a combination of the inversion symmetry breaking at the surface and the strong spin-orbit coupling of Pb atoms. The surface band structure and the spin-textures are sensitive to the surface types.

  6. Spin texture of the surface state of three-dimensional Dirac material Ca3PbO

    International Nuclear Information System (INIS)

    Kariyado, Toshikaze

    2015-01-01

    The bulk and surface electronic structures of a candidate three-dimensional Dirac material Ca 3 PbO and its family are discussed especially focusing on the spin texture on the surface states. We first explain the basic features of the bulk band structure of Ca 3 PbO, such as emergence of Dirac fermions near the Fermi energy, and compare it with the other known three-dimensional Dirac semimetals. Then, the surface bands and spin-texture on them are investigated in detail. It is shown that the surface bands exhibit strong momentum-spin locking, which may be useful in some application for spin manipulation, induced by a combination of the inversion symmetry breaking at the surface and the strong spin-orbit coupling of Pb atoms. The surface band structure and the spin-textures are sensitive to the surface types. (paper)

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. Thermosolutal convection during dendritic solidification

    Science.gov (United States)

    Heinrich, J. C.; Nandapurkar, P.; Poirier, D. R.; Felicelli, S.

    1989-01-01

    This paper presents a mathematical model for directional solidification of a binary alloy including a dendritic region underlying an all-liquid region. It is assumed initially that there exists a nonconvecting state with planar isotherms and isoconcentrates solidifying at a constant velocity. The stability of this system has been analyzed and nonlinear calculations are performed that show the effect of convection in the solidification process when the system is unstable. Results of calculations for various cases defined by the initial temperature gradient at the dendrite tips and varying strength of the gravitational field are presented for systems involving lead-tin alloys. The results show that the systems are stable for a gravitational constant of 0.0001 g(0) and that convection can be suppressed by appropriate choice of the container's size for higher values of the gravitational constant. It is also concluded that for the lead-tin systems considered, convection in the mushy zone is not significant below the upper 20 percent of the dendritic zone, if al all.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood.

    Science.gov (United States)

    Daugherty, Ana M; Flinn, Robert; Ofen, Noa

    2017-06-01

    Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution images in a sample of healthy participants (age 8-25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Human neuroimaging studies on the hippocampal CA3 region – integrating evidence for pattern separation and completion

    Directory of Open Access Journals (Sweden)

    Lorena eDeuker

    2014-03-01

    Full Text Available Human functional magnetic imaging (fMRI studies have long investigated the hippocampus without differentiating between its subfields, even though theoretical models and rodent studies suggest that subfields support different and potentially even opposite functions. The CA3 region of the hippocampus has been ascribed a pivotal role both in initially forming associations during encoding and in reconstructing a memory representation based on partial cues during retrieval. These functions have been related to pattern separation and pattern completion, respectively. In recent years, studies using high-resolution fMRI in humans have begun to separate different hippocampal subregions and identify the role of the CA3 subregion relative to the other subregions. However, some of these findings have been inconsistent with theoretical models and findings from electrophysiology. In this review, we describe selected recent studies and highlight how their results might help to define different processes and functions that are presumably carried out by the CA3 region, in particular regarding the seemingly opposing functions of pattern separation and pattern completion. We also describe how these subfield-specific processes are related to behavioral, functional and structural alterations in patients with mild cognitive impairment and Alzheimer’s disease. We conclude with discussing limitations of functional imaging and briefly outline possible future developments of the field.

  10. Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood

    Science.gov (United States)

    Daugherty, Ana M.; Flinn, Robert; Ofen, Noa

    2017-01-01

    Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution proton density-weighted images in a sample of healthy participants (age 8–25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. PMID:28342999

  11. Behavior-Dependent Activity and Synaptic Organization of Septo-hippocampal GABAergic Neurons Selectively Targeting the Hippocampal CA3 Area.

    Science.gov (United States)

    Joshi, Abhilasha; Salib, Minas; Viney, Tim James; Dupret, David; Somogyi, Peter

    2017-12-20

    Rhythmic medial septal (MS) GABAergic input coordinates cortical theta oscillations. However, the rules of innervation of cortical cells and regions by diverse septal neurons are unknown. We report a specialized population of septal GABAergic neurons, the Teevra cells, selectively innervating the hippocampal CA3 area bypassing CA1, CA2, and the dentate gyrus. Parvalbumin-immunopositive Teevra cells show the highest rhythmicity among MS neurons and fire with short burst duration (median, 38 ms) preferentially at the trough of both CA1 theta and slow irregular oscillations, coincident with highest hippocampal excitability. Teevra cells synaptically target GABAergic axo-axonic and some CCK interneurons in restricted septo-temporal CA3 segments. The rhythmicity of their firing decreases from septal to temporal termination of individual axons. We hypothesize that Teevra neurons coordinate oscillatory activity across the septo-temporal axis, phasing the firing of specific CA3 interneurons, thereby contributing to the selection of pyramidal cell assemblies at the theta trough via disinhibition. VIDEO ABSTRACT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Orientations of dendritic growth during solidification

    Science.gov (United States)

    Lee, Dong Nyung

    2017-03-01

    Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

  13. 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

  14. Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

    Directory of Open Access Journals (Sweden)

    Ballesteros KA

    2012-11-01

    Full Text Available Kristen A Ballesteros,1 Angela Sikorski,2 James E Orfila,3 Joe L Martinez Jr41Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA; 2Texas A&M University Texarkana, Texarkana, TX, USA; 3University of Colorado in Denver, Denver, CO, USA; 4University of Illinois in Chicago, Chicago, IL, USAAbstract: Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3. We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3 to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA, or 3-[(R-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP. Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals

  15. 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.

  16. Recrystallization phenomena of solution grown paraffin dendrites

    NARCIS (Netherlands)

    Hollander, F.F.A.; Hollander, F.; Stasse, O.; van Suchtelen, J.; van Enckevort, W.J.P.

    2001-01-01

    Paraffin crystals were grown from decane solutions using a micro-Bridgman set up for in-situ observation of the morphology at the growth front. It is shown that for large imposed velocities, dendrites are obtained. After dendritic growth, aging or recrystallization processes set in rather quickly,

  17. Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice.

    Science.gov (United States)

    Iñiguez, Sergio D; Aubry, Antonio; Riggs, Lace M; Alipio, Jason B; Zanca, Roseanna M; Flores-Ramirez, Francisco J; Hernandez, Mirella A; Nieto, Steven J; Musheyev, David; Serrano, Peter A

    2016-12-01

    Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days. Twenty-four h later, separate groups of mice were tested on the social interaction and tail suspension tests. Hippocampi were then dissected and Western blots were conducted to quantify protein levels for various markers important for synaptic plasticity including protein kinase M zeta (PKMζ), protein kinase C zeta (PKCζ), the dopamine-1 (D1) receptor, tyrosine hydroxylase (TH), and the dopamine transporter (DAT). Furthermore, we examined the presence of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor subunit GluA2 as well as colocalization with the post-synaptic density 95 (PSD95) protein, within different spine subtypes (filopodia, stubby, long-thin, mushroom) using an immunohistochemistry and Golgi-Cox staining technique. The results revealed that social defeat induced a depression-like behavioral profile, as inferred from decreased social interaction levels, increased immobility on the tail suspension test, and decreases in body weight. Whole hippocampal immunoblots revealed decreases in GluA2, with a concomitant increase in DAT and TH levels in the stressed group. Spine morphology analyses further showed that defeated mice displayed a significant decrease in stubby spines, and an increase in long-thin spines within the CA1 stratum radiatum. Further evaluation of GluA2/PSD95 containing-spines demonstrated a decrease of these markers within long-thin and mushroom spine types. Together, these results indicate that juvenile

  18. Repeating Spatial-Temporal Motifs of CA3 Activity Dependent on Engineered Inputs from Dentate Gyrus Neurons in Live Hippocampal Networks.

    Science.gov (United States)

    Bhattacharya, Aparajita; Desai, Harsh; DeMarse, Thomas B; Wheeler, Bruce C; Brewer, Gregory J

    2016-01-01

    Anatomical and behavioral studies, and in vivo and slice electrophysiology of the hippocampus suggest specific functions of the dentate gyrus (DG) and the CA3 subregions, but the underlying activity dynamics and repeatability of information processing remains poorly understood. To approach this problem, we engineered separate living networks of the DG and CA3 neurons that develop connections through 51 tunnels for axonal communication. Growing these networks on top of an electrode array enabled us to determine whether the subregion dynamics were separable and repeatable. We found spontaneous development of polarized propagation of 80% of the activity in the native direction from DG to CA3 and different spike and burst dynamics for these subregions. Spatial-temporal differences emerged when the relationships of target CA3 activity were categorized with to the number and timing of inputs from the apposing network. Compared to times of CA3 activity when there was no recorded tunnel input, DG input led to CA3 activity bursts that were 7× more frequent, increased in amplitude and extended in temporal envelope. Logistic regression indicated that a high number of tunnel inputs predict CA3 activity with 90% sensitivity and 70% specificity. Compared to no tunnel input, patterns of >80% tunnel inputs from DG specified different patterns of first-to-fire neurons in the CA3 target well. Clustering dendrograms revealed repeating motifs of three or more patterns at up to 17 sites in CA3 that were importantly associated with specific spatial-temporal patterns of tunnel activity. The number of these motifs recorded in 3 min was significantly higher than shuffled spike activity and not seen above chance in control networks in which CA3 was apposed to CA3 or DG to DG. Together, these results demonstrate spontaneous input-dependent repeatable coding of distributed activity in CA3 networks driven by engineered inputs from DG networks. These functional configurations at measured times

  19. Vertical solidification of dendritic binary alloys

    Science.gov (United States)

    Heinrich, J. C.; Felicelli, S.; Poirier, D. R.

    1991-01-01

    Three numerical techniques are employed to analyze the influence of thermosolutal convection on defect formation in directionally solidified (DS) alloys. The finite-element models are based on the Boussinesq approximation and include the plane-front model and two plane-front models incorporating special dendritic regions. In the second model the dendritic region has a time-independent volume fraction of liquid, and in the last model the dendritic region evolves as local conditions dictate. The finite-element models permit the description of nonlinear thermosolutal convection by treating the dendritic regions as porous media with variable porosities. The models are applied to lead-tin alloys including DS alloys, and severe segregation phenomena such as freckles and channels are found to develop in the DS alloys. The present calculations and the permeability functions selected are shown to predict behavior in the dendritic regions that qualitatively matches that observed experimentally.

  20. The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

    Directory of Open Access Journals (Sweden)

    Rossner Moritz

    2007-10-01

    Full Text Available Abstract Background The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD, RNA amplification, and array hybridization. Results Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. Conclusion The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel

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

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    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.

  2. 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.

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

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    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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

    Science.gov (United States)

    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

    2018-03-07

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Luminescent properties of Mg3Ca3(PO4)4: Eu2+ blue-emitting phosphor for white light emitting diodes

    International Nuclear Information System (INIS)

    Li Yinqun; Deng Degang; Wang Qian; Li Gaofeng; Hua Youjie; Jia Guohua; Huang Lihui; Zhao Shilong; Wang Huanping; Li Chenxia; Xu Shiqing

    2012-01-01

    A blue-emitting phosphor, Eu 2+ -activated Mg 3 Ca 3 (PO 4 ) 4 phosphor was synthesized by conventional solid-state reaction. X-ray powder diffraction (XRD) analysis confirmed the phase formation. Photoluminescence (PL) results showed that Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ could be efficiently excited by UV–visible light from 250 to 430 nm, which matched well with the emission wavelengths of near-UV and UV LED chips. The effects of the doped-Eu 2+ concentration in Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ on the PL were also investigated. The result reveals that Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ is a potential blue-emitting phosphor for white LEDs. - Graphical Abstract: The excitation spectra show a broad peak from 250 to 430 nm, which means Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ phosphor can be suitable for application in white LEDs excited by the near-UV and UV LEDs. The emission spectrum peaked at 456 nm with the full-width half-maximum (FWHM) of 102 nm is attributed to the 4f 6 5d 1 –4f 7 transition of the Eu 2+ ion. The asymmetric emission spectra show that Eu 2+ has more one emission center in Mg 3 Ca 3 (PO 4 ) 4 , which can be deconvoluted into at least four Gaussian components peaked at 423, 446, 483 and 510 nm. Highlights: ► Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ phosphor could be effectively excited by UV chips (360–430 nm). ► Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ phosphor is a potential blue-emitting phosphor for white LEDs. ► Mg 3 Ca 3 (PO 4 ) 4 : Eu 2+ phosphor shows a broadband emission.

  17. 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.

  18. Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats.

    Science.gov (United States)

    Mucio-Ramírez, Samuel; Makeyev, Oleksandr

    2017-01-01

    Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats ( n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals ( p  = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses ( p  = 0.71) nor due to the delay after the last stimulation dose ( p  = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200  μ s, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

  19. Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats

    Directory of Open Access Journals (Sweden)

    Samuel Mucio-Ramírez

    2017-01-01

    Full Text Available Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats (n=36 due to the single dose or five doses (given every 24 hours of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals (p = 0.71. Moreover, it showed no statistically significant differences due to the number of stimulation doses (p = 0.71 nor due to the delay after the last stimulation dose (p = 0.96. Obtained results suggest that stimulation at current parameters (50 mA, 200 μs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

  20. Effects of Synthesis and Processing on the Thermoelectric Properties of Ca3Co4O9+δ

    DEFF Research Database (Denmark)

    Wu, NingYu; Holgate, Tim; Van Nong, Ngo

    In the present study, Ca3Co4O9+δ was synthesized by solid-state and sol-gel reactions followed by spark plasma sintering (SPS) under different conditions such as sintering temperatures, applied pressures and ramping rates. The materials were then characterized with respect to their microstructure......, phase purity and thermoelectric properties. With the identical optimal SPS process, the power factor of about 400 µW/m•K2 and 465 µW/m•K2 (at 800 °C) is measured from samples produced by solid-state and sol-gel reactions respectively, both of these values are higher than the value reported so far....... The thermoelectric performance improvement observed for the solid-state and sol-gel reactions suggests that the particle sizes may be a predominant key parameter of the Ca3Co4O9+δ thermoelectric properties. Smaller particle size (500 nm) as produced in this study by sol-gel synthesis method with optimal SPS process...

  1. Identification of Potentially Neuroprotective Genes Upregulated by Neurotrophin Treatment of CA3 Neurons in the Injured Brain

    Science.gov (United States)

    Malik, Saafan Z.; Motamedi, Shahab; Royo, Nicolas C.; LeBold, David

    2011-01-01

    Abstract Specific neurotrophic factors mediate histological and/or functional improvement in animal models of traumatic brain injury (TBI). In previous work, several lines of evidence indicated that the mammalian neurotrophin NT-4/5 is neuroprotective for hippocampal CA3 pyramidal neurons after experimental TBI. We hypothesized that NT-4/5 neuroprotection is mediated by changes in the expression of specific sets of genes, and that NT-4/5-regulated genes are potential therapeutic targets for blocking delayed neuronal death after TBI. In this study, we performed transcription profiling analysis of CA3 neurons to identify genes regulated by lateral fluid percussion injury, or by treatment with the trkB ligands NT-4/5 or brain-derived neurotrophic factor (BDNF). The results indicate extensive overlap between genes upregulated by neurotrophins and genes upregulated by injury, suggesting that the mechanism behind neurotrophin neuroprotection may mimic the brain's endogenous protective response. A subset of genes selected for further study in vitro exhibited neuroprotection against glutamate excitotoxicity. The neuroprotective genes identified in this study were upregulated at 30 h post-injury, and are thus expected to act during a clinically useful time frame of hours to days after injury. Modulation of these factors and pathways by genetic manipulation or small molecules may confer hippocampal neuroprotection in vivo in preclinical models of TBI. PMID:21083427

  2. Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites : implications for stress-related cortical pathology?

    NARCIS (Netherlands)

    Trentani, A; Kuipers, SD; Ter Horst, GJ; Den Boer, JA

    Stress has been shown to affect brain structural plasticity, promote long-term changes in multiple neurotransmitter systems and cause neuronal atrophy. However, the mechanisms involved in these stress-related neural alterations are still poorly understood. Mitogen-activated protein kinase (MAPK)

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.)

  9. 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

  10. 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

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

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    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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations

    Directory of Open Access Journals (Sweden)

    Anja Konietzny

    2017-05-01

    Full Text Available Actin is a versatile and ubiquitous cytoskeletal protein that plays a major role in both the establishment and the maintenance of neuronal polarity. For a long time, the most prominent roles that were attributed to actin in neurons were the movement of growth cones, polarized cargo sorting at the axon initial segment, and the dynamic plasticity of dendritic spines, since those compartments contain large accumulations of actin filaments (F-actin that can be readily visualized using electron- and fluorescence microscopy. With the development of super-resolution microscopy in the past few years, previously unknown structures of the actin cytoskeleton have been uncovered: a periodic lattice consisting of actin and spectrin seems to pervade not only the whole axon, but also dendrites and even the necks of dendritic spines. Apart from that striking feature, patches of F-actin and deep actin filament bundles have been described along the lengths of neurites. So far, research has been focused on the specific roles of actin in the axon, while it is becoming more and more apparent that in the dendrite, actin is not only confined to dendritic spines, but serves many additional and important functions. In this review, we focus on recent developments regarding the role of actin in dendrite morphology, the regulation of actin dynamics by internal and external factors, and the role of F-actin in dendritic protein trafficking.

  6. 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.

  7. 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.

  8. 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.

  9. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation

    DEFF Research Database (Denmark)

    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano

    2018-01-01

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report...... pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling...... the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation....

  10. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

    Directory of Open Access Journals (Sweden)

    Catherine A Smith

    Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  11. Regulation of dendrite growth and maintenance by exocytosis

    OpenAIRE

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential req...

  12. Size and receptor density of glutamatergic synapses: a viewpoint from left-right asymmetry of CA3-CA1 connections

    Directory of Open Access Journals (Sweden)

    Yoshiaki Shinohara

    2009-07-01

    Full Text Available Synaptic plasticity is considered to be the main mechanism for learning and memory. Excitatory synapses in the cerebral cortex and hippocampus undergo plastic changes during development and in response to electric stimulation. It is widely accepted that this process is mediated by insertion and elimination of various glutamate receptors. In a series of recent investigations on left-right asymmetry of hippocampal CA3-CA1 synapses, glutamate receptor subunits have been found to have distinctive expression patterns that depend on the postsynaptic density (PSD area. Particularly notable are the GluR1 AMPA receptor subunit and NR2B NMDA receptor subunit, where receptor density has either a supra-linear (GluR1 AMPA or inverse (NR2B NMDAR relationship to the PSD area. We review current understanding of structural and physiological synaptic plasticity and propose a scheme to classify receptor subtypes by their expression pattern with respect to PSD area.

  13. X-ray spectra and electronic structure of the Ca3Ga2Ge3О12 compound

    Science.gov (United States)

    Shcherba, I. D.; Kostyk, L. V.; Noga, H.; Bekenov, L. V.; Uskokovich, D.; Jatsyk, B. M.

    2017-09-01

    The band structure of Ca3Ga2Ge3О12 with the garnet structure has been determined for the first time by X-ray emission and photoelectron spectroscopy. It has been established that the bottom of the valence band is formed by Ge d states, which are not dominant in the chemical bonding. Strong hybridization of oxygen 2s states with 4p states of Ga and Ge revealed by the presence of an extra structure in the X-ray emission spectra has been found. The middle of the valence band has been demonstrated to be occupied by d states of Ga, while Ga and Ge 4рstates with a considerable admixture of oxygen 2p states form the top of the valence band.

  14. Ih tunes theta/gamma oscillations and cross-frequency coupling in an in silico CA3 model.

    Directory of Open Access Journals (Sweden)

    Samuel A Neymotin

    Full Text Available Ih channels are uniquely positioned to act as neuromodulatory control points for tuning hippocampal theta (4-12 Hz and gamma (25 Hz oscillations, oscillations which are thought to have importance for organization of information flow. contributes to neuronal membrane resonance and resting membrane potential, and is modulated by second messengers. We investigated oscillatory control using a multiscale computer model of hippocampal CA3, where each cell class (pyramidal, basket, and oriens-lacunosum moleculare cells, contained type-appropriate isoforms of . Our model demonstrated that modulation of pyramidal and basket allows tuning theta and gamma oscillation frequency and amplitude. Pyramidal also controlled cross-frequency coupling (CFC and allowed shifting gamma generation towards particular phases of the theta cycle, effected via 's ability to set pyramidal excitability. Our model predicts that in vivo neuromodulatory control of allows flexibly controlling CFC and the timing of gamma discharges at particular theta phases.

  15. 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

  16. 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

  17. 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

  18. Dendritic ion channelopathy in acquired epilepsy

    Science.gov (United States)

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  19. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    . It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron......Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  20. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.

    Science.gov (United States)

    Noble, Emily E; Mavanji, Vijayakumar; Little, Morgan R; Billington, Charles J; Kotz, Catherine M; Wang, ChuanFeng

    2014-10-01

    Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7 weeks of exercise intervention. Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (pdiet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. Published by Elsevier Inc.

  1. Microarray profile of seizure damage-refractory hippocampal CA3 in a mouse model of epileptic preconditioning.

    Science.gov (United States)

    Hatazaki, S; Bellver-Estelles, C; Jimenez-Mateos, E M; Meller, R; Bonner, C; Murphy, N; Matsushima, S; Taki, W; Prehn, J H M; Simon, R P; Henshall, D C

    2007-12-05

    A neuroprotected state can be acquired by preconditioning brain with a stimulus that is subthreshold for damage (tolerance). Acquisition of tolerance involves coordinate, bi-directional changes to gene expression levels and the re-programmed phenotype is determined by the preconditioning stimulus. While best studied in ischemic brain there is evidence brief seizures can confer tolerance against prolonged seizures (status epilepticus). Presently, we developed a model of epileptic preconditioning in mice and used microarrays to gain insight into the transcriptional phenotype within the target hippocampus at the time tolerance had been acquired. Epileptic tolerance was induced by an episode of non-damaging seizures in adult C57Bl/6 mice using a systemic injection of kainic acid. Neuron and DNA damage-positive cell counts 24 h after status epilepticus induced by intraamygdala microinjection of kainic acid revealed preconditioning given 24 h prior reduced CA3 neuronal death by approximately 45% compared with non-tolerant seizure mice. Microarray analysis of over 39,000 transcripts (Affymetrix 430 2.0 chip) from microdissected CA3 subfields was undertaken at the point at which tolerance was acquired. Results revealed a unique profile of small numbers of equivalently up- and down-regulated genes with biological functions that included transport and localization, ubiquitin metabolism, apoptosis and cell cycle control. Select microarray findings were validated post hoc by real-time polymerase chain reaction and Western blotting. The present study defines a paradigm for inducing epileptic preconditioning in mice and first insight into the global transcriptome of the seizure-damage refractory brain.

  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. Con-nectin axons and dendrites.

    Science.gov (United States)

    Beaudoin, Gerard M J

    2006-07-03

    Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

  5. Dendritic growth forms of borax crystals

    International Nuclear Information System (INIS)

    Takoo, R.K.; Patel, B.R.; Joshi, M.S.

    1983-01-01

    A variety of dendritic forms of borax grown from solutions by the film formation method is given. The changing growth morphology is followed as a function of concentration and temperature. The initial, intermediate and final growth morphologies are described and discussed. Influence of evaporation rate and supersaturation on the mechanism of growth is assessed. It is suggested that under all crystallization conditions, borax crystals have dendritic form in the initial stages of growth. (author)

  6. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

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

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    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Effect of acetylcholine receptors on the pain-related electrical activities in the hippocampal CA3 region of morphine-addicted rats

    Directory of Open Access Journals (Sweden)

    Guan Zeng Li

    2015-07-01

    Full Text Available Objective(s:To determine the effect of acetylcholine (ACh, pilocarpine, and atropine on pain evoked responses of pain excited neurons (PEN and pain inhibited neurons (PIN in hippocampal CA3 region of morphine addicted rats. Materials and Methods:Female Wistar rats, weighing between 230-260 g were used in this study. Morphine addicted rats were generated by subcutaneous injection of increasing concentrations of morphine hydrochloride for six days. Trains of electrical impulses applied to the sciatic nerve were used as noxious stimulation and the evoked electrical activities of PEN or PIN in hippocampal CA3 area were recorded using extracellular electrophysiological recording techniques in hippocampal slices. The effect of acetylcholine receptor stimulation byACh, the muscarinic agonist pilocarpine, and the muscarinic antagonist atropine on the pain evoked responses of pain related electrical activities was analyzed in hippocampal CA3 area of morphine addicted rats. Results:Intra-CA3 microinjection of ACh (2 μg/1 μl or pilocarpine (2 μg/1 μl decreased the discharge frequency and prolonged the firing latency of PEN, but increased the discharge frequency and shortened the firing inhibitory duration (ID of PIN. The intra-CA3 administration of atropine (0.5 μg/1 μl produced opposite effect. The peak activity of cholinergic modulators was 2 to 4 min later in morphine addicted rats compared to peak activity previously observed in normal rats. Conclusion: ACh dependent modulation of noxious stimulation exists in hippocampal CA3 area of morphine addicted rats. Morphine treatment may shift the sensitivity of pain related neurons towards a delayed response to muscarinergic neurotransmission in hippocampal CA3 region.

  13. Effect of acetylcholine receptors on the pain-related electrical activities in the hippocampal CA3 region of morphine-addicted rats.

    Science.gov (United States)

    Li, Guan Zeng; Liu, Zhe Hui; Wei, XinYa; Zhao, Pan; Yang, Chun Xiao; Xu, Man Ying

    2015-07-01

    To determine the effect of acetylcholine (ACh), pilocarpine, and atropine on pain evoked responses of pain excited neurons (PEN) and pain inhibited neurons (PIN) in hippocampal CA3 region of morphine addicted rats. Female Wistar rats, weighing between 230-260 g were used in this study. Morphine addicted rats were generated by subcutaneous injection of increasing concentrations of morphine hydrochloride for six days. Trains of electrical impulses applied to the sciatic nerve were used as noxious stimulation and the evoked electrical activities of PEN or PIN in hippocampal CA3 area were recorded using extracellular electrophysiological recording techniques in hippocampal slices. The effect of acetylcholine receptor stimulation by ACh, the muscarinic agonist pilocarpine, and the muscarinic antagonist atropine on the pain evoked responses of pain related electrical activities was analyzed in hippocampal CA3 area of morphine addicted rats. Intra-CA3 microinjection of ACh (2 μg/1 μl) or pilocarpine (2 μg/1 μl) decreased the discharge frequency and prolonged the firing latency of PEN, but increased the discharge frequency and shortened the firing inhibitory duration (ID) of PIN. The intra-CA3 administration of atropine (0.5 μg/1 μl) produced opposite effect. The peak activity of cholinergic modulators was 2 to 4 min later in morphine addicted rats compared to peak activity previously observed in normal rats. ACh dependent modulation of noxious stimulation exists in hippocampal CA3 area of morphine addicted rats. Morphine treatment may shift the sensitivity of pain related neurons towards a delayed response to muscarinergic neurotransmission in hippocampal CA3 region.

  14. Dendritic cell-based immunotherapy.

    Science.gov (United States)

    Osada, Takuya; Clay, Timothy M; Woo, Christopher Y; Morse, Michael A; Lyerly, H Kim

    2006-01-01

    Dendritic cells (DCs) play a crucial role in the induction of antigen-specific T-cell responses, and therefore their use for the active immunotherapy of malignancies has been studied with considerable interest. More than a decade has passed since the publication of the first clinical data of DC-based vaccines, and through this and subsequent studies, a number of important developmental insights have been gleaned. These include the ideal source and type of DCs, the discovery of novel antigens and methods of loading DCs, the role of DC maturation, and the most efficient route of immunization. The generation of immune responses against tumor antigens after DC immunization has been demonstrated, and favorable clinical responses have been reported in some patients; however, it is difficult to pool the results as a whole, and thus the body of data remains inconclusive, in part because of varying DC preparation and vaccination protocols, the use of different forms of antigens, and, most importantly, a lack of rigorous criteria for defining clinical responses. As such, the standardization of clinical and immunologic criteria utilized, as well as DC preparations employed, will allow for the comparison of results across multiple clinical studies and is required in order for future trials to measure the true value and role of this treatment modality. In addition, issues regarding the optimal dose and clinical setting for the application of DC vaccines remain to be resolved, and recent clinical studies have been designed to begin to address these questions.

  15. Evaluation of Ca3(Co,M2O6 (M=Co, Fe, Mn, Ni as new cathode materials for solid-oxide fuel cells

    Directory of Open Access Journals (Sweden)

    Fushao Li

    2015-10-01

    Full Text Available Series compounds Ca3(Co0.9M0.12O6 (M=Co, Fe, Mn, Ni with hexagonal crystal structure were prepared by sol–gel route as the cathode materials for solid oxide fuel cells (SOFCs. Effects of the varied atomic compositions on the structure, electrical conductivity, thermal expansion and electrochemical performance were systematically evaluated. Experimental results showed that the lattice parameters of Ca3(Co0.9Fe0.12O6 and Ca3(Co0.9Mn0.12O6 were both expanded to certain degree. Electron-doping and hole-doping effects were expected in Ca3(Co0.9Mn0.12O6 and Ca3(Co0.9Ni0.12O6 respectively according to the chemical states of constituent elements and thermal-activated behavior of electrical conductivity. Thermal expansion coefficients (TEC of Ca3(Co0.9M0.12O6 were measured to be distributed around 16×10−6 K−1, and compositional elements of Fe, Mn, and Ni were especially beneficial for alleviation of the thermal expansion problem of cathode materials. By using Ca3(Co0.9M0.12O6 as the cathodes operated at 800 °C, the interfacial area-specific resistance varied in the order of M=CoCa3(Co0.9Fe0.12O6 showed the best electrochemical performance and the power density as high as ca. 500 mW cm−2 at 800 °C achieved in the single cell with La0.8Sr0.2Ga0.83Mg0.17O2.815 as electrolyte and Ni–Ce0.8Sm0.2O1.9 as anode. Ca3(Co0.9M0.12O6 (M=Co, Fe, Mn, Ni can be used as the cost-effective cathode materials for SOFCs.

  16. Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

    Science.gov (United States)

    Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

    2016-03-01

    Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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...

  19. 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...

  20. 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

  1. 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

  2. The Complete Reconfiguration of Dendritic Gold

    Science.gov (United States)

    Paneru, Govind; Flanders, Bret

    2014-03-01

    Reconfigurability-by-design is an important strategy in modern materials science, as materials with this capability could potentially be used to confer hydrophobic, lipophobic, or anti-corrosive character to substrates in a regenerative manner. The present work extends the directed electrochemical nanowire assembly (DENA) methodology, which is a technique that employs alternating voltages to grow single crystalline metallic nanowires and nano-dendrites from simple salt solutions, to enable the complete dissolution of macroscopic arrays of metallic dendrites following their growth. Our main finding is that structural reconfiguration of dendritic gold is induced by changes in the MHz-level frequencies of voltages that are applied to the dendrites. Cyclic voltammetry and micro-Raman spectroscopy have been used to show that dendritic gold grows and dissolves by the same chemical mechanisms as bulk gold. Hence, the redox chemistry that occurs at the crystal-solution interface is no different than the established electrochemistry of gold. What differs in this process and allows for reconfiguration to occur is the diffusive behavior of the gold chloride molecules in the solution adjacent to the interface. We will present a simple model that captures the physics of this behavior.

  3. 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

  4. 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

  5. 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.

  6. Growth and characterization of Nd-doped disordered Ca3Gd2(BO3)4 crystal

    Science.gov (United States)

    Pan, Z. B.; Zhang, H. J.; Yu, H. H.; Xu, M.; Zhang, Y. Y.; Sun, S. Q.; Wang, J. Y.; Wang, Q.; Wei, Z. Y.; Zhang, Z. G.

    2012-01-01

    A high-quality disordered Nd3+:Ca3Gd2(BO3)4 (Nd3+:CGB) laser crystal was grown by the Czochralski method. The space group and effective segregation coefficient of Nd3+ were determined to be Pnma and 1.06, respectively. The thermal properties, including the average linear thermal expansion coefficient, thermal diffusivity, specific heat, and thermal conductivity were systematically measured for the first time. It was found that the thermal conductivity increases with increasing temperature, indicating glasslike behavior. The polarized spectral properties of the crystal were investigated, including the polarized absorption spectra, polarized fluorescence spectra, and fluorescence decay. The spectroscopic parameters of Nd3+ ions in Nd3+:CGB crystal have been obtained based on Judd-Ofelt theory. The anisotropy of the spectral properties for different polarized directions was discussed. Additionally, the continuous-wave (CW) laser performance at 1.06 μm was demonstrated for the first time. The maximum output power of 603 mW was achieved with corresponding optical conversion efficiency of 8.33% and slope efficiency of 9.95%.

  7. HERC 1 ubiquitin ligase mutation affects neocortical, CA3 hippocampal and spinal cord projection neurons. An ultrastructural study

    Directory of Open Access Journals (Sweden)

    Rocío eRuiz

    2016-04-01

    Full Text Available The spontaneous mutation tambaleante is caused by the Gly483Glu substitution in the highly conserved N terminal RCC1-like domain of the HERC1 protein, which leads to the increase of mutated protein levels responsible for cerebellar Purkinje cell death by autophagy. Until now, Purkinje cells have been the only central nervous neurons reported as being targeted by the mutation, and their degeneration elicits an ataxic syndrome in adult mutant mice. However, the ultrastructural analysis performed here demonstrates that signs of autophagy, such as autophagosomes, lysosomes, and altered mitochondria, are present in neocortical pyramidal, CA3 hippocampal pyramidal, and spinal cord motor neurons. The main difference is that the reduction in the number of neurons affected in the tambaleante mutation in the neocortex, the hippocampus, and the spinal cord is not so evident as the dramatic loss of cerebellar Purkinje cells. Interestingly, signs of autophagy are absent in both interneurons and neuroglia cells. Affected neurons have in common that they are projection neurons which receive strong and varied synaptic inputs, and possess the highest degree of neuronal activity. Therefore, because the integrity of the ubiquitin-proteasome system is essential for protein degradation and, hence, for normal protein turnover, it could be hypothesized that the deleterious effects of the misrouting of these pathways would depend directly on the neuronal activity.

  8. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

    Science.gov (United States)

    Huang, Yang Z; Pan, Enhui; Xiong, Zhi-Qi; McNamara, James O

    2008-02-28

    The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.

  9. Polarized spectra calculation and continuous wave laser operation of Yb-doped disordered Ca3La2(BO3)4 crystal

    Science.gov (United States)

    Wang, Yeqing; Chen, Aixi; You, Zhenyu; Tu, Chaoyang

    2015-12-01

    A notable disorder crystal Yb:Ca3La2(BO3)4 crystal with Yb3+ ion doping concentration of 10 at.% was grown by the Czochralski method. The polarized absorption, polarized emission, and polarized gain cross sections were systematically calculated. The laser operations were investigated with Yb:Ca3La2(BO3)4 crystals cut along the a, b, and c crystallographic axes. The highest output power of 3.88 W was obtained by using the b-cut Yb:Ca3La2(BO3)4 crystal, with a slope efficiency of 62%. Additionally, it was confirmed that the output laser spectra were largely dependent on the output coupler.

  10. Polarized spectra calculation and continuous wave laser operation of Yb-doped disordered Ca3La2(BO3)4 crystal

    International Nuclear Information System (INIS)

    Wang, Yeqing; Chen, Aixi; You, Zhenyu; Tu, Chaoyang

    2015-01-01

    A notable disorder crystal Yb:Ca 3 La 2 (BO 3 ) 4 crystal with Yb 3+ ion doping concentration of 10 at.% was grown by the Czochralski method. The polarized absorption, polarized emission, and polarized gain cross sections were systematically calculated. The laser operations were investigated with Yb:Ca 3 La 2 (BO 3 ) 4 crystals cut along the a, b, and c crystallographic axes. The highest output power of 3.88 W was obtained by using the b-cut Yb:Ca 3 La 2 (BO 3 ) 4 crystal, with a slope efficiency of 62%. Additionally, it was confirmed that the output laser spectra were largely dependent on the output coupler. (paper)

  11. 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

  12. 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

  13. 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

  14. Structure determinations for Ca3Ti2O7, Ca4Ti3O10, Ca3.6Sr0.4Ti3O10 and a refinement of Sr3Ti2O7

    International Nuclear Information System (INIS)

    Elcombe, M.M.; Kisi, E.H.; Hawkins, K.D.; White, T.J.; Goodman, P.; Matheson, S.

    1991-01-01

    The structures of the orthorhombic Ruddlesden-Popper (A n+1 B n X 3n+1 ) phases Ca 3 Ti 2 O 7 (n=2) refined from neutron powder diffraction data at λ=1.893 A. They consist of coherent intergrowths of perovskite (CaTiO 3 ) blocks, n TiO 6 octahedra thick, with single layers of CaO having a distorted NaCl configuration. TiO 6 octahedra are tilted and distorted in a very similar fashion to those in CaTiO 3 (n=∞). This fact was used to determine the space groups of the layered structures. Convergent-beam electron diffraction patterns are best matched by calculations in the above space groups which are thus confirmed. Octahedral tilt angles increase slightly in the sequence n=2, 3, ∞. Strontium addition reduces the octahedral tilt angles because of preferential substitution of Sr on the Ca sites within the perovskite blocks of Ca 4 Ti 3 O 10 . The algorithm used to produce starting models for structure refinements is thought to be generally applicable to Ruddlesden-Popper and possibly other layered perovskite structures. It furnishes the predictions: (a) all n-even compounds in the Ca n+1 Ti n O 3n+1 series will have space group Ccm2 1 , (b) all n-odd compounds in this series will have space group Pcab, (c) all A n+1 B n X 3n+1 series for which the n=∞ end member (ABX 3 ) is isostructural with CaTiO 3 will be isostructural with the compounds reported above (e.g. Ca n+1 Zr n O 3n+1 ). (orig./WL)

  15. Stress-driven lithium dendrite growth mechanism and dendrite mitigation by electroplating on soft substrates

    Science.gov (United States)

    Wang, Xu; Zeng, Wei; Hong, Liang; Xu, Wenwen; Yang, Haokai; Wang, Fan; Duan, Huigao; Tang, Ming; Jiang, Hanqing

    2018-03-01

    Problems related to dendrite growth on lithium-metal anodes such as capacity loss and short circuit present major barriers to next-generation high-energy-density batteries. The development of successful lithium dendrite mitigation strategies is impeded by an incomplete understanding of the Li dendrite growth mechanisms, and in particular, Li-plating-induced internal stress in Li metal and its effect on Li growth morphology are not well addressed. Here, we reveal the enabling role of plating residual stress in dendrite formation through depositing Li on soft substrates and a stress-driven dendrite growth model. We show that dendrite growth is mitigated on such soft substrates through surface-wrinkling-induced stress relaxation in the deposited Li film. We demonstrate that this dendrite mitigation mechanism can be utilized synergistically with other existing approaches in the form of three-dimensional soft scaffolds for Li plating, which achieves higher coulombic efficiency and better capacity retention than that for conventional copper substrates.

  16. Ternary phosphates in Ca3(PO4)2-Na3Ln(PO4)2 (Ln-Nd, Eu, Er) systems

    International Nuclear Information System (INIS)

    Lazoryak, B.I.; Ivanov, L.N.; Strunenkova, T.V.; Golubev, V.N.; Viting, B.N.

    1990-01-01

    Ternary phosphates, formed in Ca 3 (PO 4 ) 2 -Na 3 Ln(PO 4 ) 2 (Ln-Nd, Eu, Er) systems were investigated by the methods of X-ray phase, luminescent analyses and IR spectroscopy. 5 regions of homogeneity were found. Two of them (I and II) were distinguished for all systems. Samples in the region of up to 14.285 mol.% Na 3 Ln(PO 4 ) 2 crystallize on the basis of β-Ca 3 (PO 4 ) 2 structure, and in other homogeneity regions - on the basis of β-K 2 SO 4 structure

  17. Improvement of the mechanical properties and corrosion resistance of biodegradable β-Ca3(PO4)2/Mg-Zn composites prepared by powder metallurgy: the adding β-Ca3(PO4)2, hot extrusion and aging treatment.

    Science.gov (United States)

    Yan, Yang; Kang, Yijun; Li, Ding; Yu, Kun; Xiao, Tao; Deng, Youwen; Dai, Han; Dai, Yilong; Xiong, Hanqing; Fang, Hongjie

    2017-05-01

    In this study, 10%β-Ca 3 (PO 4 ) 2 /Mg-6%Zn (wt.%) composites with Mg-6%Zn alloy as control were prepared by powder metallurgy. After hot extrusion, the as-extruded composites were aged for 72h at 150°C. The effects of the adding β-Ca 3 (PO 4 ) 2 , hot extrusion and aging treatment on their microstructure, mechanical properties and corrosion resistance were investigated. The XRD results identified α-Mg, MgZn phase and β-Ca 3 (PO 4 ) 2 phase in these composites. After hot extrusion, grains were significantly refined, and the larger-sized β-Ca 3 (PO 4 ) 2 particles and coarse MgZn phases were broken into linear-distributed β-Ca 3 (PO 4 ) 2 and MgZn phases along the extrusion direction. After aging treatment, the elements of Zn, Ca, P and O presented a more homogeneous distribution. The compressive strengths of the β-Ca 3 (PO 4 ) 2 /Mg-Zn composites were approximately double those of natural bone, and their densities and elastic moduli matched those of natural bone. The immersion tests and electrochemical tests revealed that the adding β-Ca 3 (PO 4 ) 2 , hot extrusion and aging treatment could promote the formation of protective corrosion product layer on the sample surface in Ringer's solution, which improved corrosion resistance of the β-Ca 3 (PO 4 ) 2 /Mg-Zn composites. The XRD results indicated that the corrosion product layer contained Mg(OH) 2 , β-Ca 3 (PO 4 ) 2 and hydroxyapatite (HA). The cytotoxicity assessments showed the as-extruded β-Ca 3 (PO 4 ) 2 /Mg-Zn composite aged for 72h was harmless to L-929 cells. These results suggested that the β-Ca 3 (PO 4 ) 2 /Mg-Zn composites prepared by powder metallurgy were promising to be used for bone tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Apparatus for growing a dendritic web

    International Nuclear Information System (INIS)

    Duncan, C.S.; Mchugh, J.P.; Piotrowski, P.A.; Skutch, M.E.

    1983-01-01

    A melt system including a susceptor-crucible assembly having improved gradient control when melt replenishment is used during dendritic web growth. The improvement lies in the formation of a thermal barrier in the base of the receptor which is in the form of a vertical slot in the region of the susceptor underlying the crucible at the location of a compartmental separator dividing the crucible into a growth compartment and a melt replenishment compartment. The result achieved is a step change in temperature gradient in the melt thereby providing a more uniform temperature in the growth compartment from which the dendritic web is drawn

  19. Dendrite tungsten liquation in molybdenum alloys

    International Nuclear Information System (INIS)

    Kantor, M.M.; Ageeva, E.N.; Kolotinskij, V.N.

    1992-01-01

    A study was made on primary crystallization structure of ingots of Mo-W-B system alloys with electron microscopy were used to establish, that cells and cellular dendrites were the main elements of primary crystallization structure. Method of local X-ray spectral analysis enabled to establish, that intracrystallite liquation at cellular growth developed more intensively, as compared to the case of cellular dendrite formation. Change of boron content in alloys didn't practically affect the degree of development of intracrystallite W liquation in Mo

  20. 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.)

  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

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

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    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.

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

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    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Regulation of dendrite growth and maintenance by exocytosis

    Science.gov (United States)

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382

  9. Transient potentials in dendritic systems of arbitrary geometry.

    Science.gov (United States)

    Butz, E G; Cowan, J D

    1974-09-01

    A simple graphical calculus is developed that generates analytic solutions for membrane potential transforms at any point on the dendritic tree of neurons with arbitrary dendritic geometries, in response to synaptic "current" inputs. Such solutions permit the computation of transients in neurons with arbitrary geometry and may facilitate analysis of the role of dendrites in such cells.

  10. Traumatic brain injury causes an FK506-sensitive loss and an overgrowth of dendritic spines in rat forebrain.

    Science.gov (United States)

    Campbell, John N; Register, David; Churn, Severn B

    2012-01-20

    Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24 h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24 h after TBI, however, spine density had decreased in ipsilateral neocortex in layer II and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results, together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.

  11. Anisomycin Injection in Area CA3 of the Hippocampus Impairs Both Short-Term and Long-Term Memories of Contextual Fear

    Science.gov (United States)

    Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel

    2014-01-01

    Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal…

  12. Pharmacological Intervention of Hippocampal CA3 NMDA Receptors Impairs Acquisition and Long-Term Memory Retrieval of Spatial Pattern Completion Task

    Science.gov (United States)

    Fellini, Laetitia; Florian, Cedrick; Courtey, Julie; Roullet, Pascal

    2009-01-01

    Pattern completion is the ability to retrieve complete information on the basis of incomplete retrieval cues. Although it has been demonstrated that this cognitive capacity depends on the NMDA receptors (NMDA-Rs) of the hippocampal CA3 region, the role played by these glutamatergic receptors in the pattern completion process has not yet been…

  13. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats.

    Science.gov (United States)

    Li, Ying; Ji, Yong-juan; Jiang, Hong; Liu, De-xiang; Zhang, Qian; Fan, Shu-jian; Pan, Fang

    2009-07-05

    Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Age and stress had different effects on the behavior of different aged animals (age: F = 6.173, P BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P BDNF (F = 9.408, P BDNF expression compared to the young stressed group at every testing time point. Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.

  14. Photoluminescence Properties of Red-Emitting Ca3Sr3-x(PO4)4:xEu3+ Phosphors for White Light-Emitting Diodes.

    Science.gov (United States)

    Hakeem, D A; Park, K

    2015-07-01

    The photoluminescent properties of the Eu(3+)-activated Ca3Sr3(PO4)4 phosphors prepared by a solution combustion method were investigated. The excitation spectra of Ca3Sr3-x(PO4)4:xEu3+ (0.05 ≤ x ≤ 0.6) phosphors under 614 nm wavelength showed a broad band centered at 266 nm along with other peaks at 320, 362, 381, 394, 414, 464, and 534 nm. The emission spectra observed in the range of 450 to 750 nm under excitation at 394 nm were ascribed to the 5D0-7F1-4 transitions of Eu3+ ions. The Ca3Sr3-x(PO4)4:xEu3+ phosphors showed the strongest red emission at 614 nm due to the electric dipole 5DO -->7F2 transition of Eu3+. The strongest emission intensity was obtained for the Eu3+ ions of x = 0.5. The prepared Ca3Sr3-x(PO4)4:xEu3+ can be used as an efficient red phosphor for UV-based white LEDs.

  15. Peptides and proteins in dendritic assemblies

    NARCIS (Netherlands)

    Baal, van I.

    2007-01-01

    Multiple, simultaneous interactions are often used in biology to enhance the affinity and specificity of binding, an effect referred to as multivalency. This multivalency can be mimicked by anchoring multiple peptides and proteins onto synthetic dendritic scaffolds. The aim of this research was to

  16. Targeting nanoparticles to dendritic cells for immunotherapy.

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Rueda, F.; Domingo, J.C.; Albericio, F.; Figdor, C.G.

    2012-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in

  17. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  18. Dendritic cells: biology of the skin

    NARCIS (Netherlands)

    Toebak, M.J.; Gibbs, S.; Bruynzeel, D.P.; Scheper, R.J.; Rustemeyer, T.

    2009-01-01

    Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo

  19. Thermosolutal convection and macrosegregation in dendritic alloys

    Science.gov (United States)

    Poirier, David R.; Heinrich, J. C.

    1993-01-01

    A mathematical model of solidification, that simulates the formation of channel segregates or freckles, is presented. The model simulates the entire solidification process, starting with the initial melt to the solidified cast, and the resulting segregation is predicted. Emphasis is given to the initial transient, when the dendritic zone begins to develop and the conditions for the possible nucleation of channels are established. The mechanisms that lead to the creation and eventual growth or termination of channels are explained in detail and illustrated by several numerical examples. A finite element model is used for the simulations. It uses a single system of equations to deal with the all-liquid region, the dendritic region, and the all-solid region. The dendritic region is treated as an anisotropic porous medium. The algorithm uses the bilinear isoparametric element, with a penalty function approximation and a Petrov-Galerkin formulation. The major task was to develop the solidification model. In addition, other tasks that were performed in conjunction with the modeling of dendritic solidification are briefly described.

  20. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

  1. Dendritic cells modified by vitamin D

    DEFF Research Database (Denmark)

    Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

    2011-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell ...

  2. Randomly oriented twin domains in electrodeposited silver dendrites

    Directory of Open Access Journals (Sweden)

    Ivanović Evica R.

    2015-01-01

    Full Text Available Silver dendrites were prepared by electrochemical deposition. The structures of Ag dendrites, the type of twins and their distribution were investigated by scanning electron microscopy (SEM, Z-contrast high angle annular dark field transmission electron microscopy (HAADF, and crystallografically sensitive orientation imaging microscopy (OIM. The results revealed that silver dendrites are characterized by the presence of randomly distributed 180° rotational twin domains. The broad surface of dendrites was of the {111} type. Growth directions of the main dendrite stem and all branches were of type. [Projekat Ministarstva nauke Republike Srbije, br. 172054

  3. 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...

  4. 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.)

  5. Activity-dependent trafficking of lysosomes in dendrites and dendritic spines.

    Science.gov (United States)

    Goo, Marisa S; Sancho, Laura; Slepak, Natalia; Boassa, Daniela; Deerinck, Thomas J; Ellisman, Mark H; Bloodgood, Brenda L; Patrick, Gentry N

    2017-08-07

    In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins. © 2017 Goo et al.

  6. Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus.

    Science.gov (United States)

    Hájos, N; Papp, E C; Acsády, L; Levey, A I; Freund, T F

    1998-01-01

    In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the

  7. Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task.

    Science.gov (United States)

    Martig, Adria K; Mizumori, Sheri J Y

    2011-02-01

    Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

  8. Prenatal nicotine and maternal deprivation stress de-regulate the development of CA1, CA3, and dentate gyrus neurons in hippocampus of infant rats.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC, postnatal maternal deprivation (MD or the combination of the two (NIC+MD to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14 pups, MD increased pyramidal neurons, however, in dentate gyrus (DG, decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

  9. Tricolor emission Ca3Si2O7:Ln (Ln=Ce, Tb, Eu) phosphors for near-UV white light-emitting-diode

    International Nuclear Information System (INIS)

    Mao, Zhi-yong; Zhu, Ying-chun; Gan, Lin; Zeng, Yi; Xu, Fang-fang; Wang, Yang; Tian, Hua; Li, Jian; Wang, Da-jian

    2013-01-01

    Tricolor emission in a same Ca 3 Si 2 O 7 host with independent Ln (Ln=Ce 3+ , Eu 2+ , Tb 3+ ) dopants is demonstrated to construct a near-UV white light emitting diode (LED). The luminescence properties and thermal quenching properties, as well as the applications in near-UV white LED are investigated. These phosphors show typical blue, red, and green, three-basal-color, luminescence in the CIE chromaticity diagram for Ce 3+ , Eu 2+ and Tb 3+ dopants, respectively. Thermal quenching properties show that the luminescence thermal stability strongly depends on the different dopant types; better thermal quenching property of Ce 3+ and Tb 3+ is recorded in comparison with that of Eu 2+ . The white LED prototype fabricated with near-UV chip and as-prepared tricolor phosphors exhibits acceptable CIE chromaticity coordinates (0.32, 0.30) with a CCT of 6000 K and a CRI of 87, indicating the potential application of Ca 3 Si 2 O 7 :Ln phosphors in near-UV white LED. - Highlights: ► Tricolor Ca 3 Si 2 O 7 : Ln phosphors were demonstrated to construct near-UV white LED. ► Eu 2+ doped Ca 3 Si 2 O 7 red-emitting phosphor was confirmed by this work once again. ► Thermal quenching properties for Ca 3 Si 2 O 7 :Ln phosphors were reported for the first time. ► Performances of fabricated white LED indicated the potential application of phosphors.

  10. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Oscar eHerreras

    2012-10-01

    Full Text Available Long term potentiation (LTP is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes difficult estimating the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. These indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  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. 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.

  7. 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.

  8. 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.

  9. 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)

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Shan Meltzer

    2017-10-01

    Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

  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. Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals-relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats

    DEFF Research Database (Denmark)

    Aalling, Nadia; Hageman, Ida; Miskowiak, Kamilla Woznica

    2018-01-01

    . Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor α, and heat shock protein 72, EPO increased expression of hypoxia-inducible factor-2α...... and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus....

  1. Dendritic excitability modulates dendritic information processing in a purkinje cell model.

    Science.gov (United States)

    Coop, Allan D; Cornelis, Hugo; Santamaria, Fidel

    2010-01-01

    Using an electrophysiological compartmental model of a Purkinje cell we quantified the contribution of individual active dendritic currents to processing of synaptic activity from granule cells. We used mutual information as a measure to quantify the information from the total excitatory input current (I(Glu)) encoded in each dendritic current. In this context, each active current was considered an information channel. Our analyses showed that most of the information was encoded by the calcium (I(CaP)) and calcium activated potassium (I(Kc)) currents. Mutual information between I(Glu) and I(CaP) and I(Kc) was sensitive to different levels of excitatory and inhibitory synaptic activity that, at the same time, resulted in the same firing rate at the soma. Since dendritic excitability could be a mechanism to regulate information processing in neurons we quantified the changes in mutual information between I(Glu) and all Purkinje cell currents as a function of the density of dendritic Ca (g(CaP)) and Kca (g(Kc)) conductances. We extended our analysis to determine the window of temporal integration of I(Glu) by I(CaP) and I(Kc) as a function of channel density and synaptic activity. The window of information integration has a stronger dependence on increasing values of g(Kc) than on g(CaP), but at high levels of synaptic stimulation information integration is reduced to a few milliseconds. Overall, our results show that different dendritic conductances differentially encode synaptic activity and that dendritic excitability and the level of synaptic activity regulate the flow of information in dendrites.

  2. 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.

  3. Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

    Science.gov (United States)

    Ayuob, Nasra Naeim; Firgany, Alaa El-Din L; El-Mansy, Ahmed A; Ali, Soad

    2017-10-01

    Depression is one of the important world-wide health problems. This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies. Copyright © 2017. Published by Elsevier Inc.

  4. RAB-10-Dependent Membrane Transport Is Required for Dendrite Arborization

    Science.gov (United States)

    Zou, Wei; Yadav, Smita; DeVault, Laura; Jan, Yuh Nung; Sherwood, David R.

    2015-01-01

    Formation of elaborately branched dendrites is necessary for the proper input and connectivity of many sensory neurons. Previous studies have revealed that dendritic growth relies heavily on ER-to-Golgi transport, Golgi outposts and endocytic recycling. How new membrane and associated cargo is delivered from the secretory and endosomal compartments to sites of active dendritic growth, however, remains unknown. Using a candidate-based genetic screen in C. elegans, we have identified the small GTPase RAB-10 as a key regulator of membrane trafficking during dendrite morphogenesis. Loss of rab-10 severely reduced proximal dendritic arborization in the multi-dendritic PVD neuron. RAB-10 acts cell-autonomously in the PVD neuron and localizes to the Golgi and early endosomes. Loss of function mutations of the exocyst complex components exoc-8 and sec-8, which regulate tethering, docking and fusion of transport vesicles at the plasma membrane, also caused proximal dendritic arborization defects and led to the accumulation of intracellular RAB-10 vesicles. In rab-10 and exoc-8 mutants, the trans-membrane proteins DMA-1 and HPO-30, which promote PVD dendrite stabilization and branching, no longer localized strongly to the proximal dendritic membranes and instead were sequestered within intracellular vesicles. Together these results suggest a crucial role for the Rab10 GTPase and the exocyst complex in controlling membrane transport from the secretory and/or endosomal compartments that is required for dendritic growth. PMID:26394140

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Sleeping dendrites: fiber-optic measurements of dendritic calcium activity in freely moving and sleeping animals

    Directory of Open Access Journals (Sweden)

    Julie Seibt

    2014-03-01

    Full Text Available Dendrites are the post-synaptic sites of most excitatory and inhibitory synapses in the brain, making them the main location of cortical information processing and synaptic plasticity. Although current hypotheses suggest a central role for sleep in proper cognitive function and brain plasticity, virtually nothing is known about changes in dendritic activity across the sleep-wake cycle and how waking experience modifies this activity. To start addressing these questions, we developed a method that allows long-term recordings of EEGs/EMG combined with in vivo cortical calcium (Ca2+ activity in freely moving and sleeping rats. We measured Ca2+ activity from populations of dendrites of layer (L 5 pyramidal neurons (n = 13 rats that we compared with Ca2+ activity from populations of neurons in L2/3 (n = 11 rats. L5 and L2/3 neurons were labelled using bolus injection of OGB1-AM or GCaMP6 (1. Ca2+ signals were detected using a fiber-optic system (cannula diameter = 400µm, transmitting the changes in fluorescence to a photodiode. Ca2+ fluctuations could then be correlated with ongoing changes in brain oscillatory activity during 5 major brain states: active wake [AW], quiet wake [QW], NREM, REM and NREM-REM transition (or intermediate state, [IS]. Our Ca2+ recordings show large transients in L5 dendrites and L2/3 neurons that oscillate predominantly at frequencies In summary, we show that this technique is successful in monitoring fluctuations in ongoing dendritic Ca2+ activity during natural brain states and allows, in principle, to combine behavioral measurement with imaging from various brain regions (e.g. deep structures in freely behaving animals. Using this method, we show that Ca2+ transients from populations of L2/3 neurons and L5 dendrites are deferentially regulated across the sleep/wake cycle, with dendritic activity being the highest during the IS sleep. Our correlation analysis suggests that specific sleep EEG activity during NREM and IS

  11. 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...

  12. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Directory of Open Access Journals (Sweden)

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  13. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    Science.gov (United States)

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  14. Synaptic Remodeling in the Dentate Gyrus, CA3, CA1, Subiculum, and Entorhinal Cortex of Mice: Effects of Deprived Rearing and Voluntary Running

    Directory of Open Access Journals (Sweden)

    Andrea T. U. Schaefers

    2010-01-01

    Full Text Available Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils (Meriones unguiculatus. We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice (Mus musculus. We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils.

  15. Characterization of the interface between an Fe–Cr alloy and the p-type thermoelectric oxide Ca3Co4O9

    DEFF Research Database (Denmark)

    Holgate, Tim; Han, Li; Wu, NingYu

    2014-01-01

    A customized Fe–Cr alloy that has been optimized for high temperature applications in oxidizing atmospheres has been interfaced via spark plasma sintering (SPS) with a p-type thermoelectric oxide material: calcium cobaltate (Ca3Co4O9). The properties of the al