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Sample records for stress increased amygdala

  1. Increased amygdala reactivity following early life stress: a potential resilience enhancer role.

    Science.gov (United States)

    Yamamoto, Tetsuya; Toki, Shigeru; Siegle, Greg J; Takamura, Masahiro; Takaishi, Yoshiyuki; Yoshimura, Shinpei; Okada, Go; Matsumoto, Tomoya; Nakao, Takashi; Muranaka, Hiroyuki; Kaseda, Yumiko; Murakami, Tsuneji; Okamoto, Yasumasa; Yamawaki, Shigeto

    2017-01-18

    Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Antonio Aubry

    2016-10-01

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

  4. Glucocorticoid receptor number predicts increase in amygdala activity after severe stress

    NARCIS (Netherlands)

    Geuze, Elbert; van Wingen, Guido A.; van Zuiden, Mirjam; Rademaker, Arthur R.; Vermetten, Eric; Kavelaars, Annemieke; Fernández, Guillén; Heijnen, Cobi J.

    2012-01-01

    Introduction: Individuals who are exposed to a traumatic event are at increased risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD). Studies have shown that increased amygdala activity is frequently found in patients with PTSD. In addition, pre-trauma glucocorticoid

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

    OpenAIRE

    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 w...

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

    OpenAIRE

    Antonio Aubry; Antonio Aubry; Peter Serrano; Peter Serrano; Nesha Burghardt; Nesha Burghardt

    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...

  7. Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons.

    Science.gov (United States)

    Maroun, Mouna; Ioannides, Pericles J; Bergman, Krista L; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L

    2013-08-01

    Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  8. Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons

    Science.gov (United States)

    Maroun, Mouna; Ioannides, Pericles J.; Bergman, Krista L.; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L.

    2013-01-01

    Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. PMID:23714419

  9. Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala.

    Science.gov (United States)

    Di, Shi; Itoga, Christy A; Fisher, Marc O; Solomonow, Jonathan; Roltsch, Emily A; Gilpin, Nicholas W; Tasker, Jeffrey G

    2016-08-10

    Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids in the basolateral amygdala (BLA). Cannabinoid receptors in the BLA contribute to anxiogenesis and fear-memory formation. We tested for rapid glucocorticoid-induced endocannabinoid regulation of synaptic inhibition in the rat BLA. Glucocorticoid application to amygdala slices elicited a rapid, nonreversible suppression of spontaneous, but not evoked, GABAergic synaptic currents in BLA principal neurons; the effect was also seen with a membrane-impermeant glucocorticoid, but not with intracellular glucocorticoid application, implicating a membrane-associated glucocorticoid receptor. The glucocorticoid suppression of GABA currents was not blocked by antagonists of nuclear corticosteroid receptors, or by inhibitors of gene transcription or protein synthesis, but was blocked by inhibiting postsynaptic G-protein activity, suggesting a postsynaptic nongenomic steroid signaling mechanism that stimulates the release of a retrograde messenger. The rapid glucocorticoid-induced suppression of inhibition was prevented by blocking CB1 receptors and 2-arachidonoylglycerol (2-AG) synthesis, and it was mimicked and occluded by CB1 receptor agonists, indicating it was mediated by the retrograde release of the endocannabinoid 2-AG. The rapid glucocorticoid effect in BLA neurons in vitro was occluded by prior in vivo acute stress-induced, or prior in vitro glucocorticoid-induced, release of endocannabinoid. Acute stress also caused an increase in anxiety-like behavior that was attenuated by blocking CB1 receptor activation and inhibiting 2-AG synthesis in the BLA. Together, these findings suggest that acute stress causes a long-lasting suppression of synaptic inhibition in BLA neurons via a membrane glucocorticoid receptor-induced release of 2-AG at GABA synapses, which contributes to stress-induced anxiogenesis. We provide a cellular mechanism in the basolateral amygdala (BLA) for the rapid stress

  10. Stress, memory and the amygdala.

    Science.gov (United States)

    Roozendaal, Benno; McEwen, Bruce S; Chattarji, Sumantra

    2009-06-01

    Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the efficient encoding of emotional memories can become maladaptive - severe stress often turns them into a source of chronic anxiety. Here, we review studies that have identified neural correlates of stress-induced modulation of amygdala structure and function - from cellular mechanisms to their behavioural consequences. The unique features of stress-induced plasticity in the amygdala, in association with changes in other brain regions, could have long-term consequences for cognitive performance and pathological anxiety exhibited in people with affective disorders.

  11. Increased in vivo release of neuropeptide S in the amygdala of freely moving rats after local depolarisation and emotional stress.

    Science.gov (United States)

    Ebner, Karl; Rjabokon, Alesja; Pape, Hans-Christian; Singewald, Nicolas

    2011-10-01

    Intracerebral microdialysis in conjunction with a highly sensitive radioimmunoassay was used to study the in vivo release of neuropeptide S (NPS) within the amygdala of freely moving rats. NPS was consistently detected in basolateral amygdala dialysates and the release considerably enhanced in response to local depolarisation as well as exposure to forced swim stress. Thus, our data demonstrate for the first time emotional stress-induced release of NPS in the amygdala supporting a functional role of endogenous NPS in stress/anxiety-related phenomena.

  12. Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons

    OpenAIRE

    Maroun, Mouna; Ioannides, Pericles J.; Bergman, Krista L.; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L.

    2013-01-01

    Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retrac...

  13. Stress, memory and the amygdala

    NARCIS (Netherlands)

    Roozendaal, Benno; McEwen, Bruce S.; Chattarji, Sumantra

    Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the efficient encoding of emotional memories can become maladaptive - severe stress often turns them into a source of chronic anxiety. Here, we review studies that have identified

  14. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    Science.gov (United States)

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  15. Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation.

    Science.gov (United States)

    Hoffman, Ann N; Parga, Alejandro; Paode, Pooja R; Watterson, Lucas R; Nikulina, Ella M; Hammer, Ronald P; Conrad, Cheryl D

    2015-04-01

    The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6h/d/21d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

    DEFF Research Database (Denmark)

    Maigaard, Katrine; Pedersen, Ida Hageman; Jørgensen, Anders

    2012-01-01

    Although affective disorders have high prevalence, morbidity and mortality, we do not fully understand disease etiopathology, nor have we determined the exact mechanisms by which treatment works. Recent research indicates that intracellular calcium ion dysfunction might be involved. Here we use...... the chronic restraint stress model of affective disorder (6 h restraint per day for 21 days) in combination with electroconvulsive stimulations to examine the effects of stress and an effective antidepressive treatment modality on L-type voltage gated calcium channel subunit mRNA expression patterns...... in the brain. We find that stress tended to upregulate Ca(v)1.2 and Ca(v)1.3 channels in a brain region specific manner, while ECS tended to normalise this effect. This was more pronounced for Ca(v)1.2 channels, where stress clearly increased expression in both the basolateral amygdala, dentate gyrus and CA3...

  17. Central amygdala, stress and adaption

    NARCIS (Netherlands)

    Roozendaal, Benno

    1992-01-01

    In this thesis the results were presented of studies that were designed to provide more insight in the role of the central nucleus of the amygdala (CEA) in the adaptation to environmental demands. The experiments were performed in several situations, in which rats react either directly to aversive

  18. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression

    DEFF Research Database (Denmark)

    Márquez, C; Poirier, G L; Cordero, M I

    2013-01-01

    Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress ...

  19. Association between neuroticism and amygdala responsivity emerges under stressful conditions

    NARCIS (Netherlands)

    Everaerd, Daphne; Klumpers, Floris; van Wingen, Guido; Tendolkar, Indira; Fernández, Guillén

    2015-01-01

    Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas

  20. Oxytocin increases amygdala reactivity to threatening scenes in females.

    Science.gov (United States)

    Lischke, Alexander; Gamer, Matthias; Berger, Christoph; Grossmann, Annette; Hauenstein, Karlheinz; Heinrichs, Markus; Herpertz, Sabine C; Domes, Gregor

    2012-09-01

    The neuropeptide oxytocin (OT) is well known for its profound effects on social behavior, which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli. In humans, OT decreases amygdala reactivity to threatening faces in males, but enhances amygdala reactivity to similar faces in females, suggesting sex-specific differences in OT-dependent threat-processing. To further explore whether OT generally enhances amygdala-dependent threat-processing in females, we used functional magnetic resonance imaging (fMRI) in a randomized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo. Participants' eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features. Although OT had no effect on participants' gazing behavior, it increased amygdala reactivity to scenes depicting social and non-social threat. In females, OT may, thus, enhance the detection of threatening stimuli in the environment, potentially by interacting with gonadal steroids, such as progesterone and estrogen. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. A neuroplasticity hypothesis of chronic stress in the basolateral amygdala.

    Science.gov (United States)

    Boyle, Lara M

    2013-06-01

    Chronic stress plays a role in the etiology of several affective and anxiety-related disorders. Despite this, its mechanistic effects on the brain are still unclear. Of particular interest is the effect of chronic stress on the amygdala, which plays a key role in the regulation of emotional responses and memory consolidation. This review proposes a neuroplasticity model for the effects of chronic stress in this region, emphasizing the roles of glutamate and BDNF signaling. This model provides a review of recent discoveries of the effects of chronic stress in the amygdala and reveals pathways for future research.

  2. Intrinsic functional connectivity between amygdala and hippocampus during rest predicts enhanced memory under stress.

    Science.gov (United States)

    de Voogd, Lycia D; Klumpers, Floris; Fernández, Guillén; Hermans, Erno J

    2017-01-01

    Declarative memories of stressful events are less prone to forgetting than mundane events. Animal research has demonstrated that such stress effects on consolidation of hippocampal-dependent memories require the amygdala. In humans, it has been shown that during learning, increased amygdala-hippocampal interactions are related to more efficient memory encoding. Animal models predict that following learning, amygdala-hippocampal interactions are instrumental to strengthening the consolidation of such declarative memories. Whether this is the case in humans is unknown and remains to be empirically verified. To test this, we analyzed data from a sample of 120 healthy male participants who performed an incidental encoding task and subsequently underwent resting-state functional MRI in a stressful and a neutral context. Stress was assessed by measures of salivary cortisol, blood pressure, heart rate, and subjective ratings. Memory was tested afterwards outside of the scanner. Our data show that memory was stronger in the stress context compared to the neutral context and that stress-induced cortisol responses were associated with this memory enhancement. Interestingly, amygdala-hippocampal connectivity during post-encoding awake rest regardless of context (stress or neutral) was associated with the enhanced memory performance under stress. Thus, our findings are in line with a role for intrinsic functional connectivity during rest between the amygdala and the hippocampus in the state effects of stress on strengthening memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial.

    Science.gov (United States)

    Taren, Adrienne A; Gianaros, Peter J; Greco, Carol M; Lindsay, Emily K; Fairgrieve, April; Brown, Kirk Warren; Rosen, Rhonda K; Ferris, Jennifer L; Julson, Erica; Marsland, Anna L; Bursley, James K; Ramsburg, Jared; Creswell, J David

    2015-12-01

    Recent studies indicate that mindfulness meditation training interventions reduce stress and improve stress-related health outcomes, but the neural pathways for these effects are unknown. The present research evaluates whether mindfulness meditation training alters resting state functional connectivity (rsFC) of the amygdala, a region known to coordinate stress processing and physiological stress responses. We show in an initial discovery study that higher perceived stress over the past month is associated with greater bilateral amygdala-subgenual anterior cingulate cortex (sgACC) rsFC in a sample of community adults (n = 130). A follow-up, single-blind randomized controlled trial shows that a 3-day intensive mindfulness meditation training intervention (relative to a well-matched 3-day relaxation training intervention without a mindfulness component) reduced right amygdala-sgACC rsFC in a sample of stressed unemployed community adults (n = 35). Although stress may increase amygdala-sgACC rsFC, brief training in mindfulness meditation could reverse these effects. This work provides an initial indication that mindfulness meditation training promotes functional neuroplastic changes, suggesting an amygdala-sgACC pathway for stress reduction effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. Blunted amygdala functional connectivity during a stress task in alcohol dependent individuals: A pilot study

    Directory of Open Access Journals (Sweden)

    Natasha E. Wade, M.S.

    2017-12-01

    Full Text Available Background: Scant research has been conducted on neural mechanisms underlying stress processing in individuals with alcohol dependence (AD. We examined neural substrates of stress in AD individuals compared with controls using an fMRI task previously shown to induce stress, assessing amygdala functional connectivity to medial prefrontal cortex (mPFC. Materials and methods: For this novel pilot study, 10 abstinent AD individuals and 11 controls completed a modified Trier stress task while undergoing fMRI acquisition. The amygdala was used as a seed region for whole-brain seed-based functional connectivity analysis. Results: After controlling for family-wise error (p = 0.05, there was significantly decreased left and right amygdala connectivity with frontal (specifically mPFC, temporal, parietal, and cerebellar regions. Subjective stress, but not craving, increased from pre-to post-task. Conclusions: This study demonstrated decreased connectivity between the amygdala and regions important for stress and emotional processing in long-term abstinent individuals with AD. These results suggest aberrant stress processing in individuals with AD even after lengthy periods of abstinence. Keywords: Alcohol dependence, fMRI, Stress task, Functional connectivity, Amygdala

  5. Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala.

    Science.gov (United States)

    Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian

    2012-06-01

    Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety-like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to pre-conditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction.

  6. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

    2015-11-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

  7. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

    2015-01-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

  8. Intrinsic functional connectivity between amygdala and hippocampus during rest predicts enhanced memory under stress

    NARCIS (Netherlands)

    Voogd, L.D. de; Klumpers, F.; Fernandez, G.; Hermans, E.

    2017-01-01

    Declarative memories of stressful events are less prone to forgetting than mundane events. Animal research has demonstrated that such stress effects on consolidation of hippocampal-dependent memories require the amygdala. In humans, it has been shown that during learning, increased

  9. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  10. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    Science.gov (United States)

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Blunted amygdala functional connectivity during a stress task in alcohol dependent individuals: A pilot study.

    Science.gov (United States)

    Wade, Natasha E; Padula, Claudia B; Anthenelli, Robert M; Nelson, Erik; Eliassen, James; Lisdahl, Krista M

    2017-12-01

    Scant research has been conducted on neural mechanisms underlying stress processing in individuals with alcohol dependence (AD). We examined neural substrates of stress in AD individuals compared with controls using an fMRI task previously shown to induce stress, assessing amygdala functional connectivity to medial prefrontal cortex (mPFC). For this novel pilot study, 10 abstinent AD individuals and 11 controls completed a modified Trier stress task while undergoing fMRI acquisition. The amygdala was used as a seed region for whole-brain seed-based functional connectivity analysis. After controlling for family-wise error (p = 0.05), there was significantly decreased left and right amygdala connectivity with frontal (specifically mPFC), temporal, parietal, and cerebellar regions. Subjective stress, but not craving, increased from pre-to post-task. This study demonstrated decreased connectivity between the amygdala and regions important for stress and emotional processing in long-term abstinent individuals with AD. These results suggest aberrant stress processing in individuals with AD even after lengthy periods of abstinence.

  12. Evidence for smaller right amygdala volumes in posttraumatic stress disorder following childhood trauma

    NARCIS (Netherlands)

    Veer, I.M.; Oei, N.Y.L.; van Buchem, M.A.; Spinhoven, Ph.; Elzinga, B.M.; Rombouts, S.A.R.B.

    2015-01-01

    Hippocampus and amygdala volumes in posttraumatic stress disorder (PTSD) related to childhood trauma are relatively understudied, albeit the potential importance to the disorder. Whereas some studies reported smaller hippocampal volumes, little evidence was found for abnormal amygdala volumes. Here

  13. ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

    Science.gov (United States)

    Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

    2015-02-01

    Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

  14. Effects of early life stress on amygdala and striatal development.

    Science.gov (United States)

    Fareri, Dominic S; Tottenham, Nim

    2016-06-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one's social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Effects of early life stress on amygdala and striatal development

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri

    2016-06-01

    Full Text Available Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS in the form of the absence of species expected caregiving (i.e., caregiver deprivation, can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction.

  16. Effects of early life stress on amygdala and striatal development

    Science.gov (United States)

    Fareri, Dominic S.; Tottenham, Nim

    2016-01-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. PMID:27174149

  17. Increased amygdala response to shame in remitted major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Erdem Pulcu

    Full Text Available Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD, and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8. This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15. Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

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

    OpenAIRE

    Sharp, B M

    2017-01-01

    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 neuro...

  19. Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala.

    Science.gov (United States)

    Zhang, Wei; Rosenkranz, J Amiel

    2016-08-01

    The adolescent age is associated with lability of mood and emotion. The onset of depression and anxiety disorders peaks during adolescence and there are differences in symptomology during adolescence. This points to differences in the adolescent neural circuitry that underlies mood and emotion, such as the amygdala. The human adolescent amygdala is more responsive to evocative stimuli, hinting to less local inhibitory regulation of the amygdala, but this has not been explored in adolescents. The amygdala, including the lateral nucleus (LAT) of the basolateral amygdala complex, is sensitive to stress. The amygdala undergoes maturational processes during adolescence, and therefore may be more vulnerable to harmful effects of stress during this time period. However, little is known about the effects of stress on the LAT during adolescence. GABAergic inhibition is a key regulator of LAT activity. Therefore, the purpose of this study was to test whether there are differences in the local GABAergic regulation of the rat adolescent LAT, and differences in its sensitivity to repeated stress. We found that LAT projection neurons are subjected to weaker GABAergic inhibition during adolescence. Repeated stress reduced in vivo endogenous and exogenous GABAergic inhibition of LAT projection neurons in adolescent rats. Furthermore, repeated stress decreased measures of presynaptic GABA function and interneuron activity in adolescent rats. In contrast, repeated stress enhanced glutamatergic drive of LAT projection neurons in adult rats. These results demonstrate age differences in GABAergic regulation of the LAT, and age differences in the mechanism for the effects of repeated stress on LAT neuron activity. These findings provide a substrate for increased mood lability in adolescents, and provide a substrate by which adolescent repeated stress can induce distinct behavioral outcomes and psychiatric symptoms.

  20. Prevention of Stress-Impaired Fear Extinction Through Neuropeptide S Action in the Lateral Amygdala

    OpenAIRE

    Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian

    2012-01-01

    Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fe...

  1. Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma.

    Science.gov (United States)

    Stevens, Jennifer S; Kim, Ye Ji; Galatzer-Levy, Isaac R; Reddy, Renuka; Ely, Timothy D; Nemeroff, Charles B; Hudak, Lauren A; Jovanovic, Tanja; Rothbaum, Barbara O; Ressler, Kerry J

    2017-06-15

    Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for posttraumatic stress disorder (PTSD); however, our understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospective study of PTSD. Participants were recruited from the emergency department of a large level I trauma center within 24 hours of trauma. PTSD symptoms were assessed at baseline and approximately 1, 3, 6, and 12 months after trauma. Growth curve modeling was used to estimate symptom recovery trajectories. Thirty-one individuals participated in functional magnetic resonance imaging around the 1-month assessment, passively viewing fearful and neutral face stimuli. Reactivity (fearful > neutral) and habituation to fearful faces was examined. Amygdala reactivity, but not habituation, 5 to 12 weeks after trauma was positively associated with the PTSD symptom intercept and predicted symptoms at 12 months after trauma. Habituation in the ventral anterior cingulate cortex was positively associated with the slope of PTSD symptoms, such that decreases in ventral anterior cingulate cortex activation over repeated presentations of fearful stimuli predicted increasing symptoms. Findings point to neural signatures of risk for maintaining PTSD symptoms after trauma exposure. Specifically, chronic symptoms were predicted by amygdala hyperreactivity, and poor recovery was predicted by a failure to maintain ventral anterior cingulate cortex activation in response to fearful stimuli. The importance of identifying patients at risk after trauma exposure is discussed. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli.

    Science.gov (United States)

    Redlich, Ronny; Stacey, David; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Kugel, Harald; Heindel, Walter; Arolt, Volker; Baune, Bernhard T; Dannlowski, Udo

    2015-12-01

    Since numerous studies have found that exposure to early life stress leads to increased peripheral inflammation and psychiatric disease, it is thought that peripheral immune activation precedes and possibly mediates the onset of stress-associated psychiatric disease. Despite early studies, IFNγ has received little attention relative to other inflammatory cytokines in the context of the pathophysiology of affective disorders. Neuroimaging endophenotypes have emerged recently as a promising means of elucidating these types of complex relationships including the modeling of the interaction between environmental factors and genetic predisposition. Here we investigate the GxE relationship between early-life stress and genetic variants of IFNγ on emotion processing. To investigate the impact of the relationship between genetic variants of IFNγ (rs1861494, rs2069718, rs2430561) and early life stress on emotion processing, a sample of healthy adults (n=409) undergoing an emotional faces paradigm in an fMRI study were genotyped and analysed. Information on early life stress was obtained via Childhood Trauma Questionnaire (CTQ). A positive association between early life stress and amygdala reactivity was found. Specifically, the main effect of genotype of rs1861494 on amygdala reactivity indicates a higher neural response in C allele carriers compared to T homozygotes, while we did not find main effects of rs2069718 and rs2430561. Importantly, interaction analyses revealed a specific interaction between IFNγ genotype (rs1861494) and early life stress affecting amygdala reactivity to emotional faces, resulting from a positive association between CTQ scores and amygdala reactivity in C allele carriers while this association was absent in T homozygotes. Our findings indicate that firstly the genetic variant of IFNγ (rs1861494) is involved with the regulation of amygdala reactivity to emotional stimuli and secondly, that this genetic variant moderates effects of early life

  3. Posttraumatic stress and alcohol use among veterans: Amygdala and anterior cingulate activation to emotional cues.

    Science.gov (United States)

    Simons, Raluca M; Simons, Jeffrey S; Olson, Dawne; Baugh, Lee; Magnotta, Vincent; Forster, Gina

    2016-11-01

    This fMRI study tested a model of combat trauma, posttraumatic stress symptoms (PTSS), alcohol use, and behavioral and neural responses to emotional cues in 100 OIF/OEF/OND veterans. Multilevel structural equation models were tested for left and right dorsal ACC (dACC), rostral ACC (rACC), and amygdala blood-oxygen- level dependent responses during the emotional counting Stroop test and masked faces task. In the Stroop task, combat exposure moderated the effect of combat stimuli resulting in hyperactivation in the rACC and dACC. Activation in the left amygdala also increased in response to combat stimuli, but effects did not vary as a function of combat severity. In the masked faces task, activation patterns did not vary as a function of stimulus. However, at the between-person level, amygdala activation during the masked faces task was inversely associated with PTSS. In respect to behavioral outcomes, higher PTSS were associated with a stronger Stroop effect, suggesting greater interference associated with combat words. Results are consistent with the premise that combat trauma results in hyperactivation in the ACC in response to combat stimuli, and, via its effect on PTSS, is associated with deficits in cognitive performance in the presence of combat stimuli. Across tasks, predeployment drinking was inversely associated with activation in the dACC but not the rACC or amygdala. Drinking may be a buffering factor, or negatively reinforcing in part because of its effects on normalizing brain response following trauma exposure. Alternatively, drinking may undermine adaptive functioning of the dACC when responding to traumatic stress cues. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  4. High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults.

    Science.gov (United States)

    Clark, Uraina S; Sweet, Lawrence H; Morgello, Susan; Philip, Noah S; Cohen, Ronald A

    2017-06-01

    Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); HIV+ High-ELS (N = 13); HC Low-ELS (N = 16); and HC High-ELS (N = 9). Participants completed a battery of neuropsychiatric measures. BOLD fMRI assessed amygdala reactivity during explicit observation of fearful/angry faces. High-ELS participants demonstrated reduced levels of amygdala reactivity relative to Low-ELS participants. HIV+ High-ELS participants reported higher levels of neuropsychiatric symptoms than all other groups. In the HIV+ group, lower amygdala responses were associated with higher neuropsychiatric symptoms, particularly depression, anxiety, and alexithymia. Collectively, these results suggest that high ELS exposure is a significant risk factor for neuropsychiatric symptoms in HIV+ adults. Furthermore, our results implicate ELS-related abnormalities in amygdala activity in the etiology of neuropsychiatric symptoms in HIV+ adults.

  5. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

    Science.gov (United States)

    Ehrlich, David E.; Neigh, Gretchen N.; Bourke, Chase H.; Nemeth, Christina L.; Hazra, Rimi; Ryan, Steven J.; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney; Rainnie, Donald G.; Stowe, Zachary N.; Owens, Michael J.

    2015-01-01

    Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436

  6. Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping

    Directory of Open Access Journals (Sweden)

    Vito Salvador Hernandez

    2016-11-01

    Full Text Available The arginine-vasopressin (AVP-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs are known for their role in hydro-electrolytic balance control via their projections to neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula, and other brain regions, in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA. The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS, consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN and supraoptic (SON nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptors mRNA were not detected, using the same method. Water-deprivation for 24 hrs, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze test, and this effect was mimicked by bilateral microinfusion of VP into the CeA. Anxious behavior induced by either water deprivation or VP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of central amygdala inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

  7. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

    Directory of Open Access Journals (Sweden)

    Harini Lakshminarasimhan

    Full Text Available Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day causes growth of dendrites and spines in the basolateral amygdala (BLA, but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  8. Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.

    Science.gov (United States)

    Nicholson, Andrew A; Sapru, Iman; Densmore, Maria; Frewen, Paul A; Neufeld, Richard W J; Théberge, Jean; McKinnon, Margaret C; Lanius, Ruth A

    2016-04-30

    The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD-DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.

    Science.gov (United States)

    Aghajani, Moji; Veer, Ilya M; van Hoof, Marie-José; Rombouts, Serge A R B; van der Wee, Nic J; Vermeiren, Robert R J M

    2016-03-01

    Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets. © 2016 Wiley Periodicals, Inc.

  10. Impact of sleep quality on amygdala reactivity, negative affect, and perceived stress.

    Science.gov (United States)

    Prather, Aric A; Bogdan, Ryan; Hariri, Ahmad R

    2013-05-01

    Research demonstrates a negative impact of sleep disturbance on mood and affect; however, the biological mechanisms mediating these links are poorly understood. Amygdala reactivity to negative stimuli has emerged as one potential pathway. Here, we investigate the influence of self-reported sleep quality on associations between threat-related amygdala reactivity and measures of negative affect and perceived stress. Analyses on data from 299 participants (125 men, 50.5% white, mean [standard deviation] age = 19.6 [1.3] years) who completed the Duke Neurogenetics Study were conducted. Participants completed several self-report measures of negative affect and perceived stress. Threat-related (i.e., angry and fearful facial expressions) amygdala reactivity was assayed using blood oxygen level-dependent functional magnetic resonance imaging. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Amygdala reactivity to fearful facial expressions predicted greater depressive symptoms and higher perceived stress in poor (β values = 0.18-1.86, p values .05). In sex-specific analyses, men reporting poorer global sleep quality showed a significant association between amygdala reactivity and levels of depression and perceived stress (β values = 0.29-0.44, p values sleep quality or in women, irrespective of sleep quality. This study provides novel evidence that self-reported sleep quality moderates the relationships between amygdala reactivity, negative affect, and perceived stress, particularly among men.

  11. Post-traumatic stress and age variation in amygdala volumes among youth exposed to trauma.

    Science.gov (United States)

    Weems, Carl F; Klabunde, Megan; Russell, Justin D; Reiss, Allan L; Carrión, Victor G

    2015-12-01

    Theoretically, normal developmental variation in amygdala volumes may be altered under conditions of severe stress. The purpose of this article was to examine whether posttraumatic stress moderates the association between age and amygdala volumes in youth exposed to traumatic events who are experiencing symptoms of post-traumatic stress disorder (PTSD). Volumetric imaging was conducted on two groups of youth aged 9-17 years: 28 with exposure to trauma and PTSD symptoms (boys = 15, girls = 13) and 26 matched (age, IQ) comparison youth (Controls; boys = 12, girls = 14). There was a significant group by age interaction in predicting right amygdala volumes. A positive association between age and right amygdala volumes was observed, but only in PTSD youth. These associations with age remained when controlling for IQ, total brain volumes and sex. Moreover, older youth with PTSD symptoms had relatively larger right amygdala volumes than controls. Findings provide evidence that severe stress may influence age-related variation in amygdala volumes. Results further highlight the importance of utilizing age as an interactive variable in pediatric neuroimaging research, in so far as age may act as an important moderator of group differences. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Occlusal Disharmony Transiently Impairs Learning and Memory in the Mouse by Increasing Dynorphin A Levels in the Amygdala.

    Science.gov (United States)

    Yamada, Kentaro; Ono, Yumie; Kubo, Kin-Ya; Yamamoto, Toshiharu; Onozuka, Minoru

    2013-05-01

    Occlusal disharmony sometimes causes not only stiffness of neck but also psychiatric depression, suggesting that the condition of oral cavity may affect the central nervous system. Dynorphin A is an endogenous opioid peptide that specifically binds the κ-opioid receptor and has a protective role against stress. Dynorphinergic nervous system is intensely distributed in the amygdala and hippocampus that are coping areas with stress. As a model of malocclusion, we placed dental resin on the molars to increase the occlusal vertical dimension (bite-raise). After various survival times, we analyzed the amygdala and hippocampus by immunohistochemistry and immunosorbent assay (ELISA). Furthermore, the effects on learning and memory were assessed by Morris water maze test. In the amygdala, the levels of dynorphin A were increased on the 1st day after increasing the vertical dimension as indicated by immunohistochemical and ELISA assessments. The levels of dynorphin A returned to control levels on the 5th day. In the hippocampus, there were no noticeable changes in dynorphin A levels. The water maze test indicated that increasing the vertical dimension caused longer escape latency times on the 3rd day compared to those of sham-operated group. However, the bite-raised mice treated with a dynorphin antagonist, nor-binaltorphimine, showed similar escape latency times to the times of sham-operated group, even on the 3rd day. These results suggest that occlusal disharmony causes stress resulting in a transient increase of dynorphin A levels at least in the amygdala and that the increased dynorphin A levels transiently impair learning and memory.

  13. Neuroimaging study of the human amygdala. Toward an understanding of emotional and stress responses

    International Nuclear Information System (INIS)

    Iidaka, Tetsuya

    2007-01-01

    The amygdala plays a critical role in the neural system involved in emotional responses and conditioned fear. The dysfunction of this system is thought to be a cause of several neuropsychiatric disorders. A neuroimaging study provides a unique opportunity for noninvasive investigation of the human amygdala. We studied the activity of this structure in normal subjects and patients with schizophrenia by using the face recognition task. Our results showed that the amygdala was activated by presentation of face stimuli, and negative face activated the amygdala to a greater extent than a neutral face. Under the happy face condition, the activation of the amygdala was higher in the schizophrenic patients than in control subjects. A single nucleotide polymorphism in the regulatory region of the serotonin type 3 receptor gene had modulatory effects on the amygdaloid activity. The emotion regulation had a significant impact on neural interaction between the amygdala and prefrontal cortices. Thus, studies on the human amygdala would greatly contribute to the elucidation of the neural system that determines emotional and stress responses. To clarify the relevance of the neural dysfunction and neuropsychiatric disorders, further studies using physiological, genetic, and hormonal approaches are essential. (author)

  14. Neuroimaging Study of the Human Amygdala - Toward an Understanding of Emotional and Stress Responses -

    Science.gov (United States)

    Iidaka, Tetsuya

    The amygdala plays a critical role in the neural system involved in emotional responses and conditioned fear. The dysfunction of this system is thought to be a cause of several neuropsychiatric disorders. A neuroimaging study provides a unique opportunity for noninvasive investigation of the human amygdala. We studied the activity of this structure in normal subjects and patients with schizophrenia by using the face recognition task. Our results showed that the amygdala was activated by presentation of face stimuli, and negative face activated the amygdala to a greater extent than a neutral face. Under the happy face condition, the activation of the amygdala was higher in the schizophrenic patients than in control subjects. A single nucleotide polymorphism in the regulatory region of the serotonin type 3 receptor gene had modulatory effects on the amygdaloid activity. The emotion regulation had a significant impact on neural interaction between the amygdala and prefrontal cortices. Thus, studies on the human amygdala would greatly contribute to the elucidation of the neural system that determines emotional and stress responses. To clarify the relevance of the neural dysfunction and neuropsychiatric disorders, further studies using physiological, genetic, and hormonal approaches are essential.

  15. Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

    Science.gov (United States)

    Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

    2016-07-01

    Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.

    Science.gov (United States)

    Sarro, E C; Sullivan, R M; Barr, G

    2014-01-31

    Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

    Science.gov (United States)

    Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

    2017-06-01

    Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences.

    Science.gov (United States)

    Roozendaal, Benno; Barsegyan, Areg; Lee, Sangkwan

    2008-01-01

    Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine or glucocorticoids administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences. Our findings indicate that adrenal stress hormones influence memory consolidation via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala. In turn, the amygdala regulates memory consolidation via its efferent projections to many other brain regions. In contrast to the enhancing effects on consolidation, high circulating levels of stress hormones impair memory retrieval and working memory. Such effects also require noradrenergic activation of the amygdala and interactions with other brain regions.

  19. NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

    2018-05-26

    Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

  20. 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.

  1. Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala.

    Science.gov (United States)

    Koenigs, Michael; Grafman, Jordan

    2009-10-01

    Posttraumatic stress disorder (PTSD) is characterized by recurrent distressing memories of an emotionally traumatic event. In this review, the authors present neuroscientific data highlighting the function of two brain areas--the amygdala and ventromedial prefrontal cortex (vmPFC)--in PTSD and related emotional processes. A convergent body of human and nonhuman studies suggests that the amygdala mediates the acquisition and expression of conditioned fear and the enhancement of emotional memory, whereas the vmPFC mediates the extinction of conditioned fear and the volitional regulation of negative emotion. It has been theorized that the vmPFC exerts inhibition on the amygdala, and that a defect in this inhibition could account for the symptoms of PTSD. This theory is supported by functional imaging studies of PTSD patients, who exhibit hypoactivity in the vmPFC but hyperactivity in the amygdala. A recent study of brain-injured and trauma-exposed combat veterans confirms that amygdala damage reduces the likelihood of developing PTSD. But contrary to the prediction of the top-down inhibition model, vmPFC damage also reduces the likelihood of developing PTSD. The putative roles of the amygdala and the vmPFC in the pathophysiology of PTSD, as well as implications for potential treatments, are discussed in light of these results.

  2. Impairment of fear memory consolidation in maternally stressed male mouse offspring: evidence for nongenomic glucocorticoid action on the amygdala.

    Science.gov (United States)

    Lee, Eun Jeong; Son, Gi Hoon; Chung, Sooyoung; Lee, Sukwon; Kim, Jeongyeon; Choi, Sukwoo; Kim, Kyungjin

    2011-05-11

    The environment in early life elicits profound effects on fetal brain development that can extend into adulthood. However, the long-lasting impact of maternal stress on emotional learning remains largely unknown. Here, we focus on amygdala-related learning processes in maternally stressed mice. In these mice, fear memory consolidation and certain related signaling cascades were significantly impaired, though innate fear, fear memory acquisition, and synaptic NMDA receptor expression in the amygdala were unaltered. In accordance with these findings, maintenance of long-term potentiation (LTP) at amygdala synapses, but not its induction, was significantly impaired in the maternally stressed animals. Interestingly, amygdala glucocorticoid receptor expression was reduced in the maternally stressed mice, and administration of glucocorticoids (GCs) immediately after fear conditioning and LTP induction restored memory consolidation and LTP maintenance, respectively, suggesting that a weakening of GC signaling was responsible for the observed impairment. Furthermore, microinfusion of a membrane-impermeable form of GC (BSA-conjugated GC) into the amygdala mimicked the restorative effects of GC, indicating that a nongenomic activity of GC mediates the restorative effect. Together, these findings suggest that prenatal stress induces long-term dysregulation of nongenomic GC action in the amygdala of adult offspring, resulting in the impairment of fear memory consolidation. Since modulation of amygdala activity is known to alter the consolidation of emotionally influenced memories allocated in other brain regions, the nongenomic action of GC on the amygdala shown herein may also participate in the amygdala-dependent modulation of memory consolidation.

  3. 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.

  4. Impact of Sleep Quality on Amygdala Reactivity, Negative Affect, and Perceived Stress

    Science.gov (United States)

    Prather, Aric A.; Bogdan, Ryan; Ahmad R. Hariri, PhD

    2013-01-01

    Objective Research demonstrates a negative impact of sleep disturbance on mood and affect; however, the biological mechanisms mediating these links are poorly understood. Amygdala reactivity to negative stimuli has emerged as one potential pathway. Here, we investigate the influence of self-reported sleep quality on associations between threat-related amygdala reactivity and measures of negative affect and perceived stress. Methods Analyses on data from 299 participants (125 men, 50.5% white, mean [standard deviation] age = 19.6 [1.3] years) who completed the Duke Neurogenetics Study were conducted. Participants completed several self-report measures of negative affect and perceived stress. Threat-related (i.e., angry and fearful facial expressions) amygdala reactivity was assayed using blood oxygen level–dependent functional magnetic resonance imaging. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results Amygdala reactivity to fearful facial expressions predicted greater depressive symptoms and higher perceived stress in poor (β values = 0.18–1.86, p values .05). In sex-specific analyses, men reporting poorer global sleep quality showed a significant association between amygdala reactivity and levels of depression and perceived stress (β values = 0.29–0.44, p values < .05). In contrast, no significant associations were observed in men reporting good global sleep quality or in women, irrespective of sleep quality. Conclusions This study provides novel evidence that self-reported sleep quality moderates the relationships between amygdala reactivity, negative affect, and perceived stress, particularly among men. PMID:23592753

  5. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Roseman, Leor; Demetriou, Lysia; Wall, Matthew B; Nutt, David J; Carhart-Harris, Robin L

    2017-12-27

    Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. ISRCTN, number ISRCTN14426797. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. 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

  7. Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

    Directory of Open Access Journals (Sweden)

    Ewan eMcNay

    2015-11-01

    Full Text Available Recurrent hypoglycemia (RH is a common and debilitating side effect of therapy in patients with both type 1 and, increasingly, type 2 diabetes. Previous studies in rats have shown marked effects of RH on subsequent hippocampal behavioral, metabolic, and synaptic processes. In addition to impaired memory, patients experiencing RH report alterations in cognitive processes that include mood and anxiety, suggesting that RH may also affect amygdala function. We tested the impact of RH on amygdala function using an elevated plus-maze test of anxiety together with in vivo amygdala microdialysis for norepinephrine (NEp, a widely used marker of basolateral amygdala cognitive processes. In contrast to findings in the hippocampus and pre-frontal cortex, neither RH nor acute hypoglycemia alone significantly affected plus-maze performance or NEp release. However, animals tested when hypoglycemic who had previously experienced RH had elevated amygdala NEp during plus-maze testing, accompanied by increased anxiety (i.e. less time spent in the open arms of the plus-maze. The results show that RH has widespread effects on subsequent brain function, which vary by neural system.

  8. Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation

    NARCIS (Netherlands)

    Atsak, P.; Hauer, D.; Campolongo, P.; Schelling, G.; Fornari, R.V.; Roozendaal, B.

    2015-01-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory

  9. Neonatal Amygdala Lesions and Stress Responsivity in Rats : Relevance to schizophrenia

    NARCIS (Netherlands)

    Terpstra, Jeroen

    2004-01-01

    "Stress responsiveness in an animal model with relevance to schizophrenia” Rats bearing lesions of the amygdala made on postnatal day 7 (D7 AMX) model aspects of neurodevelopmental psychopathologies, such as schizophrenia. Adult D7 AMX rats display impaired pre-pulse inhibition, impaired

  10. Activation of ERK2 in basolateral amygdala underlies the promoting influence of stress on fear memory and anxiety: influence of midazolam pretreatment.

    Science.gov (United States)

    Maldonado, N M; Espejo, P J; Martijena, I D; Molina, V A

    2014-02-01

    Exposure to emotionally arousing experiences elicits a robust and persistent memory and enhances anxiety. The amygdala complex plays a key role in stress-induced emotional processing and in the fear memory formation. It is well known that ERK activation in the amygdala is a prerequisite for fear memory consolidation. Moreover, stress elevates p-ERK2 levels in several areas of the brain stress circuitry. Therefore, given that the ERK1/2 cascade is activated following stress and that the role of this cascade is critical in the formation of fear memory, the present study investigated the potential involvement of p-ERK2 in amygdala subnuclei in the promoting influence of stress on fear memory formation and on anxiety-like behavior. A robust and persistent ERK2 activation was noted in the Basolateral amygdala (BLA), which was evident at 5min after restraint and lasted at least one day after the stressful experience. Midazolam, a short-acting benzodiazepine ligand, administered prior to stress prevented the increase in the p-ERK2 level in the BLA. Pretreatment with intra-BLA infusion of U0126 (MEK inhibitor), but not into the adjacent central nucleus of the amygdala, attenuated the stress-induced promoting influence on fear memory formation. Finally, U0126 intra-BLA infusion prevented the enhancement of anxiety-like behavior in stressed animals. These findings suggest that the selective ERK2 activation in BLA following stress exposure is an important mechanism for the occurrence of the promoting influence of stress on fear memory and on anxiety-like behavior. © 2013 Published by Elsevier B.V. and ECNP.

  11. Anxiolytic-Like Effects of Increased Ghrelin Receptor Signaling in the Amygdala

    DEFF Research Database (Denmark)

    Jensen, Morten; Ratner, Cecilia; Rudenko, Olga

    2016-01-01

    BACKGROUND: Besides the well-known effects of ghrelin on adiposity and food intake regulation, the ghrelin system has been shown to regulate aspects of behavior including anxiety and stress. However, the effect of virus-mediated overexpression of the ghrelin receptor in the amygdala has...... not previously been addressed directly. METHOD: First, we examined the acute effect of peripheral ghrelin administration on anxiety- and depression-like behavior using the open field, elevated plus maze, forced swim and tail suspension tests. Next, we examined the effect of peripheral ghrelin administration...... and ghrelin receptor deficiency on stress in a familiar and social environment using the Intellicage system. Importantly, we also used a novel approach to study ghrelin receptor signaling in the brain by overexpressing the ghrelin receptor in the amygdala. We examined the effect of ghrelin receptor...

  12. 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.

  13. Repeated homotypic stress elevates 2-arachidonoylglycerol levels and enhances short-term endocannabinoid signaling at inhibitory synapses in basolateral amygdala.

    Science.gov (United States)

    Patel, Sachin; Kingsley, Philip J; Mackie, Ken; Marnett, Lawrence J; Winder, Danny G

    2009-12-01

    Psychosocial stress is a risk factor for development and exacerbation of neuropsychiatric illness. Repeated stress causes biochemical adaptations in endocannabinoid (eCB) signaling that contribute to stress-response habituation, however, the synaptic correlates of these adaptations have not been examined. Here, we show that the synthetic enzyme for the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol (DAG) lipase alpha, is heterogeneously expressed in the amygdala, and that levels of 2-AG and precursor DAGs are increased in the basolateral amygdala (BLA) after 10 days, but not 1 day, of restraint stress. In contrast, arachidonic acid was decreased after both 1 and 10 days of restraint stress. To examine the synaptic correlates of these alterations in 2-AG metabolism, we used whole-cell electrophysiology to determine the effects of restraint stress on depolarization-induced suppression of inhibition (DSI) in the BLA. A single restraint stress exposure did not alter DSI compared with control mice. However, after 10 days of restraint stress, DSI duration, but not magnitude, was significantly prolonged. Inhibition of 2-AG degradation with MAFP also prolonged DSI duration; the effects of repeated restraint stress and MAFP were mutually occlusive. These data indicate that exposure to repeated, but not acute, stress produces neuroadaptations that confer BLA neurons with an enhanced capacity to elevate 2-AG content and engage in 2-AG-mediated short-term retrograde synaptic signaling. We suggest stress-induced enhancement of eCB-mediated suppression of inhibitory transmission in the BLA could contribute to affective dysregulation associated with chronic stress.

  14. The effect of basolateral amygdala nucleus lesion on memory under acute,mid and chronic stress in male rats.

    Science.gov (United States)

    Ranjbar, Hoda; Radahmadi, Maryam; Alaei, Hojjatallah; Reisi, Parham; Karimi, Sara

    2016-12-20

    The basolateral amygdala (BLA) modulates memory for emotional events and is involved in both stress and memory. This study investigated different durations of stress and the role of BLA on serum corticosterone level and spatial and cognitive memory. Different durations of stress (acute, mid, and chronic stress), with and without BLA lesion were induced in rats by 6 h/day restraint stress for 1, 7, and 21 days. Memory functions were evaluated by novel object recognition (NOR) and object location test (OLT). The OLT findings showed locomotor activity and spatial memory slightly decreased with different durations of stress. The NOR findings significantly showed locomotor activity impairment in different durations of stress. Cognitive memory deficit was observed in mid stress. The corticosterone level significantly increased in the mid and chronic stress groups. Moreover, the mid stress was the strongest stress condition. There is a possibility that different stress durations act by different mechanisms. The recognition of a novel location decreased in all lesion groups. It was more severe in the NOR. The BLA lesion significantly decreased corticosterone level in the mid and chronic stress groups compared to similar groups without lesion. The BLA lesion caused more damage to cognitive than spatial memory in stressed groups.

  15. Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

    Science.gov (United States)

    Weir, R K; Bauman, M D; Jacobs, B; Schumann, C M

    2018-02-01

    The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD. © 2017 Wiley Periodicals, Inc.

  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. Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress.

    Science.gov (United States)

    Klein, Rebecca C; Acheson, Shawn K; Qadri, Laura H; Dawson, Alina A; Rodriguiz, Ramona M; Wetsel, William C; Moore, Scott D; Laskowitz, Daniel T; Dawson, Hana N

    2016-06-01

    Traumatic brain injury (TBI) is a leading cause of death and disability among young adults and is highly prevalent among recently deployed military personnel. Survivors of TBI often experience cognitive and emotional deficits, suggesting that long-term effects of injury may disrupt neuronal function in critical brain regions, including the amygdala, which is involved in emotion and fear memory. Amygdala hyperexcitability has been reported in both TBI and posttraumatic stress disorder patients, yet little is known regarding the effects of combined stress and TBI on amygdala structure and function at the neuronal level. The present study seeks to determine how the long-term effects of preinjury foot-shock stress and TBI interact to influence synaptic plasticity in the lateral amygdala (LA) of adult male C57BL/6J mice by using whole-cell patch clamp electrophysiology 2-3 months postinjury. In the absence of stress, TBI resulted in a significant increase in membrane excitability and spontaneous excitatory postsynaptic currents (sEPSCs) in LA pyramidal-like neurons. Foot-shock stress in the absence of TBI also resulted in increased sEPSC activity. In contrast, when preinjury stress and TBI occurred in combination, sEPSC activity was significantly decreased compared with either condition alone. There were no significant differences in inhibitory activity or total dendritic length among any of the treatment groups. These results demonstrate that stress and TBI may be contributing to amygdala hyperexcitability via different mechanisms and that these pathways may counterbalance each other with respect to long-term pathophysiology in the LA. © 2015 Wiley Periodicals, Inc.

  18. Decreased expression of extracellular matrix proteins and trophic factors in the amygdala complex of depressed mice after chronic immobilization stress

    Directory of Open Access Journals (Sweden)

    Jung Soonwoong

    2012-06-01

    Full Text Available Abstract Background The amygdala plays an essential role in controlling emotional behaviors and has numerous connections to other brain regions. The functional role of the amygdala has been highlighted by various studies of stress-induced behavioral changes. Here we investigated gene expression changes in the amygdala in the chronic immobilization stress (CIS-induced depression model. Results Eight genes were decreased in the amygdala of CIS mice, including genes for neurotrophic factors and extracellular matrix proteins. Among these, osteoglycin, fibromodulin, insulin-like growth factor 2 (Igf2, and insulin-like growth factor binding protein 2 (Igfbp2 were further analyzed for histological expression changes. The expression of osteoglycin and fibromodulin simultaneously decreased in the medial, basolateral, and central amygdala regions. However, Igf2 and Igfbp2 decreased specifically in the central nucleus of the amygdala. Interestingly, this decrease was found only in the amygdala of mice showing higher immobility, but not in mice displaying lower immobility, although the CIS regimen was the same for both groups. Conclusions These results suggest that the responsiveness of the amygdala may play a role in the sensitivity of CIS-induced behavioral changes in mice.

  19. Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala.

    Science.gov (United States)

    Wu, Zhong-Min; Ni, Gui-Lian; Shao, Ai-Min; Cui, Rong

    2017-09-01

    Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder, characterized by intense fear, and increased arousal and avoidance of traumatic events. The current available treatments for PTSD have limited therapeutic value. Genistein, a natural isoflavone, modulates a variety of cell functions. In this study, we tested anti-anxiety activity and underlying mechanisms of genistein in a PTSD rat model. The rats were trained to associate a tone with foot shock delivery on day 0, then fear conditioning was performed on day 7, 14 and 21. Genistein (2-8mg/kg) was injected intraperitoneally daily for 7 days. The anti-anxiety effects of genistein were measured by contextual freezing behavior and elevated plus maze. By the end of the experiments, the amygdala was extracted and subject to neurochemistry analysis. Genistein alleviated contextual freezing behavior and improved performance in elevated plus maze dose-dependently in PTSD rats. Furthermore, in these rats, genistein enhanced serotonergic transmission in the amygdala, including upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB, as well. Genistein exerts anti-anxiety effects on a PTSD model probably through enhancing serotonergic system and CaMKII/CREB signaling pathway in the amygdala. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

    NARCIS (Netherlands)

    Koch, Saskia B. J.; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

    2016-01-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single

  1. Increases in extracellular zinc in the amygdala in acquisition and recall of fear experience and their roles in response to fear.

    Science.gov (United States)

    Takeda, A; Tamano, H; Imano, S; Oku, N

    2010-07-14

    The amygdala is enriched with histochemically reactive zinc, which is dynamically coupled with neuronal activity and co-released with glutamate. The dynamics of the zinc in the amygdala was analyzed in rats, which were subjected to inescapable stress, to understand the role of the zinc in emotional behavior. In the communication box, two rats were subjected to foot shock stress and anxiety stress experiencing emotional responses of foot-shocked rat under amygdalar perfusion. Extracellular zinc was increased by foot shock stress, while decreased by anxiety stress, suggesting that the differential changes in extracellular zinc are associated with emotional behavior. In rats conditioned with foot shock, furthermore, extracellular zinc was increased again in the recall of fear (foot shock) in the same box without foot shock. When this recall was performed under perfusion with CaEDTA, a membrane-impermeable zinc chelator, to examine the role of the increase in extracellular zinc, the time of freezing behavior was more increased, suggesting that zinc released in the lateral amygdala during the recall of fear participates in freezing behavior. To examine the role of the increase in extracellular zinc during fear conditioning, fear conditioning was also performed under perfusion with CaEDTA. The time of freezing behavior was more increased in the contextual recall, suggesting that zinc released in the lateral nucleus during fear conditioning also participates in freezing behavior in the recall. In brain slice experiment, CaEDTA enhanced presynaptic activity (exocytosis) in the lateral nucleus after activation of the entorhinal cortex. The present paper demonstrates that zinc released in the lateral amygdala may participate in emotional behavior in response to fear. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    Science.gov (United States)

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  4. Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants.

    Science.gov (United States)

    Goldstein-Piekarski, Andrea N; Korgaonkar, Mayuresh S; Green, Erin; Suppes, Trisha; Schatzberg, Alan F; Hastie, Trevor; Nemeroff, Charles B; Williams, Leanne M

    2016-10-18

    Amygdala circuitry and early life stress (ELS) are both strongly and independently implicated in the neurobiology of depression. Importantly, animal models have revealed that the contribution of ELS to the development and maintenance of depression is likely a consequence of structural and physiological changes in amygdala circuitry in response to stress hormones. Despite these mechanistic foundations, amygdala engagement and ELS have not been investigated as biobehavioral targets for predicting functional remission in translational human studies of depression. Addressing this question, we integrated human neuroimaging and measurement of ELS within a controlled trial of antidepressant outcomes. Here we demonstrate that the interaction between amygdala activation engaged by emotional stimuli and ELS predicts functional remission on antidepressants with a greater than 80% cross-validated accuracy. Our model suggests that in depressed people with high ELS, the likelihood of remission is highest with greater amygdala reactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, remission is associated with lower amygdala reactivity to both rewarding and threat-related stimuli. This full model predicted functional remission over and above the contribution of demographics, symptom severity, ELS, and amygdala reactivity alone. These findings identify a human target for elucidating the mechanisms of antidepressant functional remission and offer a target for developing novel therapeutics. The results also offer a proof-of-concept for using neuroimaging as a target for guiding neuroscience-informed intervention decisions at the level of the individual person.

  5. Neurobiological Programming of Early Life Stress: Functional Development of Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related Psychopathology.

    Science.gov (United States)

    VanTieghem, Michelle R; Tottenham, Nim

    2017-04-25

    Early adverse experiences are associated with heighted vulnerability for stress-related psychopathology across the lifespan. While extensive work has investigated the effects of early adversity on neurobiology in adulthood, developmental approaches can provide further insight on the neurobiological mechanisms that link early experiences and long-term mental health outcomes. In the current review, we discuss the role of emotion regulation circuitry implicated in stress-related psychopathology from a developmental and transdiagnostic perspective. We highlight converging evidence suggesting that multiple forms of early adverse experiences impact the functional development of amygdala-prefrontal circuitry. Next, we discuss how adversity-induced alterations in amygdala-prefrontal development are associated with symptoms of emotion dysregulation and psychopathology. Additionally, we discuss potential mechanisms through which protective factors may buffer the effects of early adversity on amygdala-prefrontal development to confer more adaptive long-term outcomes. Finally, we consider limitations of the existing literature and make suggestions for future longitudinal and translational research that can better elucidate the mechanisms linking early adversity, neurobiology, and emotional phenotypes. Together, these findings may provide further insight into the neuro-developmental mechanisms underlying the emergence of adversity-related emotional disorders and facilitate the development of targeted interventions that can ameliorate risk for psychopathology in youth exposed to early life stress.

  6. Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder.

    Science.gov (United States)

    Patel, Ronak; Girard, Todd A; Pukay-Martin, Nicole; Monson, Candice

    2016-04-01

    The vast majority of functional neuroimaging studies in posttraumatic stress disorder (PTSD) have examined the amygdala as a unitary structure. However, an emerging body of studies indicates that separable functions are subserved by discrete amygdala subregions. The basolateral subdivision (BLA), as compared with the centromedial amygdala (CMA), plays a unique role in learning and memory-based processes for threatening events, and alterations to the BLA have been implicated in the pathogenesis of PTSD. We assessed whether PTSD is associated with differential involvement of the BLA versus the CMA during successful encoding of emotionally charged events. Participants with PTSD (n=11) and a trauma-exposed comparison (TEC) group (n=11) viewed a series of photos that varied in valence (negative versus positive) and arousal (high versus low) while undergoing functional magnetic resonance imaging (fMRI). Subsequently, participants completed an old/new recognition memory test. Using analytic methods based on probabilistic cytoarchitectonic mapping, PTSD was associated with greater activation of the BLA, as compared to the CMA, during successful encoding of negative scenes, a finding which was not observed in the TEC group. Moreover, this memory-related activity in the BLA independently predicted PTSD status. Contrary to hypotheses, there was no evidence of altered BLA activity during memory encoding of high arousing relative to low arousing scenes. Task-related brain activation in PTSD does not appear to be consistent across the entire amygdala. Importantly, memory-related processing of negative information in PTSD is associated with preferential recruitment of the BLA. Copyright © 2016. Published by Elsevier Inc.

  7. Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

    Science.gov (United States)

    Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

    2018-01-04

    Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  8. Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

    Science.gov (United States)

    Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

    2017-10-01

    Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

  9. Stress impairs reconsolidation of drug memory via glucocorticoid receptors in the basolateral amygdala.

    Science.gov (United States)

    Wang, Xiao-Yi; Zhao, Mei; Ghitza, Udi E; Li, Yan-Qin; Lu, Lin

    2008-05-21

    Relapse to drug taking induced by exposure to cues associated with drugs of abuse is a major challenge to the treatment of drug addiction. Previous studies indicate that drug seeking can be inhibited by disrupting the reconsolidation of a drug-related memory. Stress plays an important role in modulating different stages of memory including reconsolidation, but its role in the reconsolidation of a drug-related memory has not been investigated. Here, we examined the effects of stress and corticosterone on reconsolidation of a drug-related memory using a conditioned place preference (CPP) procedure. We also determined the role of glucocorticoid receptors (GRs) in the basolateral amygdala (BLA) in modulating the effects of stress on reconsolidation of this memory. We found that rats acquired morphine CPP after conditioning, and that this CPP was inhibited by stress given immediately after re-exposure to a previously morphine-paired chamber (a reconsolidation procedure). The disruptive effect of stress on reconsolidation of morphine related memory was prevented by inhibition of corticosterone synthesis with metyrapone or BLA, but not central amygdala (CeA), injections of the glucocorticoid (GR) antagonist RU38486 [(11,17)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one]. Finally, the effect of stress on drug related memory reconsolidation was mimicked by systemic injections of corticosterone or injections of RU28362 [11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one] (a GR agonist) into BLA, but not the CeA. These results show that stress blocks reconsolidation of a drug-related memory, and this effect is mediated by activation of GRs in the BLA.

  10. Prefrontal cortex or basolateral amygdala lesions blocked the stress-induced inversion of serial memory retrieval pattern in mice.

    Science.gov (United States)

    Chauveau, F; Piérard, C; Coutan, M; Drouet, I; Liscia, P; Béracochéa, D

    2008-09-01

    Previous data from our team have shown that pre-test stress in mice reversed the pattern of memory retrieval in a contextual serial spatial task (CSD; Celerier, A., Pierard, C., Rachbauer, D., Sarrieau, A., & Beracochea, D. (2004). Contextual and serial discriminations: A new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice. Learning and Memory, 11, 196-204). The present study is aimed at determining brain areas which might be critically involved in mediating the stress effect on memory retrieval in the CSD task. For that purpose, we studied hereby the effects of ibotenic acid lesions of either the prefrontal cortex (PFC) or the basolateral amygdala (BLA) in Stressed or Non-Stressed Balb/c mice on memory retrieval in the CSD task. In that task, mice learned two successive spatial discriminations (D1 and D2) within two different internal contexts in a four-hole board. The stressor (electric footshocks) was delivered 5 min before test, occurring 24 h after acquisition. During test, mice were relocated either on the floor of the first or of the second discrimination. Results showed that (i) spatial memory was substantial and remained unaffected both by lesions and stress; (ii) Non-Stressed controls as well as Non-Stressed or Stressed PFC and BLA-lesioned mice remembered accurately D1 but not D2; and (iii) in contrast, Stressed controls accurately remembered D2 but not D1. In parallel to behavioral experiments, we also showed that PFC and BLA lesions did not affect the stress-induced increase of plasma corticosterone levels. All together, PFC and BLA integrity are not necessary for retrieval processes per se; in contrast, the PFC and BLA are critically involved in the mediation of the deleterious stress effects on serial order memory retrieval.

  11. Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA (A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.

    Science.gov (United States)

    Wu, Guofeng; Wang, Likun; Hong, Zhen; Ren, Siying; Zhou, Feng

    2017-08-01

    The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats). A stimulation electrode was implanted into the hippocampus of all of the rats. Hip-LFS was administered twice per day in the PRS group for two weeks. Simultaneously, amygdala stimulus-induced seizures and afterdischarge were recorded. After the hippocampal stimulation was terminated, the brain tissues were obtained to determine the GABA (A) receptors by a method of immumohistochemistry and a real-time polymerase chain reaction. The stages and duration of the amygdala stimulus-induced epileptic seizures were decreased in the PRS group. The afterdischarge threshold was increased and the duration as well as the afterdischarge frequency was decreased. Simultaneously, the GABA (A) expression was significantly increased in the PRS group. Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects of hippocampal stimulation may be partly achieved by increasing the GABA (A) receptor.

  12. Repeated social stress leads to contrasting patterns of structural plasticity in the amygdala and hippocampus.

    Science.gov (United States)

    Patel, D; Anilkumar, S; Chattarji, S; Buwalda, B

    2018-03-23

    Previous studies have demonstrated that repeated immobilization and restraint stress cause contrasting patterns of dendritic reorganization as well as alterations in spine density in amygdalar and hippocampal neurons. Whether social and ethologically relevant stressors can induce similar patterns of morphological plasticity remains largely unexplored. Hence, we assessed the effects of repeated social defeat stress on neuronal morphology in basolateral amygdala (BLA), hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats experienced social defeat stress on 5 consecutive days during confrontation in the resident-intruder paradigm with larger and aggressive Wild-type Groningen rats. This resulted in clear social avoidance behavior one day after the last confrontation. To assess the morphological consequences of repeated social defeat, 2 weeks after the last defeat, animals were sacrificed and brains were stained using a Golgi-Cox procedure. Morphometric analyses revealed that, compared to controls, defeated Wistar rats showed apical dendritic decrease in spine density on CA1 but not BLA. Sholl analysis demonstrated a significant dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in defeated animals. Social stress failed to induce lasting structural changes in mPFC neurons. Our findings demonstrate for the first time that social defeat stress elicits divergent patterns of structural plasticity in the hippocampus versus amygdala, similar to what has previously been reported with repeated physical stressors. Therefore, brain region specific variations may be a universal feature of stress-induced plasticity that is shared by both physical and social stressors. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Impaired fear extinction in serotonin transporter knockout rats is associated with increased 5-hydroxymethylcytosine in the amygdala

    NARCIS (Netherlands)

    Shan, L.; Guo, Hang-Yuan; van den Heuvel, Corina N A M; van Heerikhuize, J.J.; Homberg, Judith R

    2018-01-01

    AIMS: One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA

  14. Dysfunctional or hyperfunctional? The amygdala in posttraumatic stress disorder is the bull in the evolutionary China shop.

    Science.gov (United States)

    Diamond, David M; Zoladz, Phillip R

    2016-06-01

    Our motivation in writing this Review arose not only from the great value in contributing to this special issue of the Journal of Neuroscience Research but also from the desire to express our opinion that the description of the amygdala as "dysfunctional" in posttraumatic stress disorder (PTSD) might not be appropriate. We acknowledge that excessive activation of the amygdala contributes to the cluster of PTSD symptoms, including hypervigilance, intrusive memories, and impaired sleep, that underlies the devastating mental and physical outcomes in trauma victims. The issue that we address is whether the symptoms of PTSD represent an impaired (dysfunctional) or sensitized (hyperfunctional) amygdala status. We propose that the amygdala in PTSD is hyperfunctional rather than dysfunctional in recognition of the fact that the individual has already survived one life-threatening attack and that another may be forthcoming. We therefore consider PTSD to be a state in which the amygdala is functioning optimally if the goal is to ensure a person's survival. The misery caused by a hyperfunctional amygdala in PTSD is the cost of inheriting an evolutionarily primitive mechanism that considers survival more important than the quality of one's life. © 2015 Wiley Periodicals, Inc.

  15. Smaller amygdala volume and reduced anterior cingulate gray matter density associated with history of post-traumatic stress disorder.

    Science.gov (United States)

    Rogers, Mark A; Yamasue, Hidenori; Abe, Osamu; Yamada, Haruyasu; Ohtani, Toshiyuki; Iwanami, Akira; Aoki, Shigeki; Kato, Nobumasa; Kasai, Kiyoto

    2009-12-30

    Although post-traumatic stress disorder (PTSD) may be seen to represent a failure to extinguish learned fear, significant aspects of the pathophysiology relevant to this hypothesis remain unknown. Both the amygdala and hippocampus are necessary for fear extinction occur, and thus both regions may be abnormal in PTSD. Twenty-five people who experienced the Tokyo subway sarin attack in 1995, nine who later developed PTSD and 16 who did not, underwent magnetic resonance imaging (MRI) with manual tracing to determine bilateral amygdala and hippocampus volumes. At the time of scanning, one had PTSD and eight had a history of PTSD. Results indicated that the group with a history of PTSD had significantly smaller mean bilateral amygdala volume than did the group that did not develop PTSD. Furthermore, left amygdala volume showed a significant negative correlation with severity of PTSD symptomatology as well as reduced gray matter density in the left anterior cingulate cortex. To our knowledge, this is the first observation of an association between PTSD and amygdala volume. Furthermore the apparent interplay between amygdala and anterior cingulate cortex represents support at the level of gross brain morphology for the theory of PTSD as a failure of fear extinction.

  16. Stress-induced resistance to the fear memory labilization/reconsolidation process. Involvement of the basolateral amygdala complex.

    Science.gov (United States)

    Espejo, Pablo Javier; Ortiz, Vanesa; Martijena, Irene Delia; Molina, Victor Alejandro

    2016-10-01

    Consolidated memories can enter into a labile state after reactivation followed by a restabilization process defined as reconsolidation. This process can be interfered with Midazolam (MDZ), a positive allosteric modulator of the GABA-A receptor. The present study has evaluated the influence of prior stress on MDZ's interfering effect. We also assessed the influence of both systemic and intra-basolateral amygdala (BLA) infusion of d-cycloserine (DCS), a partial agonist of the NMDA receptors, on the MDZ effect in previously stressed rats. Furthermore, we analyzed the effect of stress on the expression of Zif-268 and the GluN2B sites, two molecular markers of the labilization/reconsolidation process, following reactivation. The results revealed that prior stress resulted into a memory trace that was insensitive to the MDZ impairing effect. Both systemic and intra-BLA DCS administration previous to reactivation restored MDZ's disruptive effect on memory reconsolidation in stressed animals. Further, reactivation enhanced Zif-268 expression in the BLA in control unstressed rats, whereas no elevation was observed in stressed animals. In agreement with the behavioral findings, DCS restored the increased level of Zif-268 expression in the BLA in stressed animals. Moreover, memory reactivation in unstressed animals elevated GluN2B expression in the BLA, thus suggesting that this effect is involved in memory destabilization, whereas stressed animals did not reveal any changes. These findings are consistent with resistance to the MDZ effect in these rats, indicating that stress exposure prevents the onset of destabilization following reactivation. In summary, prior stress limited both the occurrence of the reactivation-induced destabilization and restabilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway.

    Science.gov (United States)

    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G; Mungenast, Alison E; Deisseroth, Karl; Tsai, Li-Huei

    2015-06-09

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.

  18. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

    Science.gov (United States)

    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G.; Mungenast, Alison E.; Deisseroth, Karl; Tsai, Li-Huei

    2015-01-01

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation. PMID:25995364

  19. Neuropeptide S and BDNF gene expression in the amygdala are influenced by social decision-making under stress

    Directory of Open Access Journals (Sweden)

    Justin P. Smith

    2014-04-01

    Full Text Available In a newly developed conceptual model of stressful social decision making, the Stress-Alternatives Model (SAM; used for the 1st time in mice elicits two types of response: escape or remain submissively. Daily (4d aggressive social interaction in a neutral arena between a C57BL6/N test mouse and a larger, novel aggressive CD1 mouse, begin after an audible tone (conditioned stimulus; CS. Although escape holes (only large enough for smaller test animals are available, and the aggressor is unremittingly antagonistic, only half of the mice tested utilize the possibility of escape. During training, for mice that choose to leave the arena and social interaction, latency to escape dramatically decreases over time; this is also true for control C57BL6/N mice which experienced no aggression. Therefore, the open field of the SAM apparatus is intrinsically anxiogenic. It also means that submission to the aggressor is chosen despite this anxiety and the high intensity of the aggressive attacks and defeat. While both groups that received aggression displayed stress responsiveness, corticosterone levels were significantly higher in animals that chose submissive coexistence. Although both escaping and non-escaping groups of animals experienced aggression and defeat, submissive animals also exhibited classic fear conditioning, freezing in response to the CS alone, while escaping animals did not. In the basolateral amygdala, gene expression of BDNF was diminished, but NPS expression was significantly elevated, but only in submissive animals. This increase in submission-evoked NPS mRNA expression was greatest in the central amygdala, which coincided with decreased BDNF expression. Reduced expression of BDNF is only in submissive animals that also exhibit elevated NPS expression, despite elevated corticosterone in all socially interacting animals. The results suggest an interwoven relationship, linked by social context, between amygdalar BDNF, NPS and plasma

  20. Avoidant Responses to Interpersonal Provocation Are Associated with Increased Amygdala and Decreased Mentalizing Network Activity

    Science.gov (United States)

    Krämer, Ulrike M.

    2017-01-01

    When intentionally pushed or insulted, one can either flee from the provoker or retaliate. The implementation of such fight-or-flight decisions is a central aspect in the genesis and evolution of aggression episodes, yet it is usually investigated only indirectly or in nonsocial situations. In the present fMRI study, we aimed to distinguish brain regions associated with aggressive and avoidant responses to interpersonal provocation in humans. Participants (thirty-six healthy young women) could either avoid or face a highly (HP) and a lowly (LP) provoking opponent in a competitive reaction time task: the fight-or-escape (FOE) paradigm. Subjects avoided the HP more often, but retaliated when facing her. Moreover, they chose to fight the HP more quickly, and showed increased heart rate (HR) right before confronting her. Orbitofrontal cortex (OFC) and sensorimotor cortex were more active when participants decided to fight, whereas the mentalizing network was engaged when deciding to avoid. Importantly, avoiding the HP relative to the LP was associated with both higher activation in the right basolateral amygdala and lower relative activity in several mentalizing regions [e.g., medial and inferior frontal gyrus (IFG), temporal-parietal junction (TPJ)]. These results suggest that avoidant responses to provocation might result from heightened threat anticipation and are associated with reduced perspective taking. Furthermore, our study helps to reconcile conflicting findings on the role of the mentalizing network, the amygdala, and the OFC in aggression. PMID:28660251

  1. Effects of Optogenetic inhibition of BLA on Sleep Brief Optogenetic Inhibition of the Basolateral Amygdala in Mice Alters Effects of Stressful Experiences on Rapid Eye Movement Sleep.

    Science.gov (United States)

    Machida, Mayumi; Wellman, Laurie L; Fitzpatrick Bs, Mairen E; Hallum Bs, Olga; Sutton Bs, Amy M; Lonart, György; Sanford, Larry D

    2017-04-01

    Stressful events can directly produce significant alterations in subsequent sleep, in particular rapid eye movement sleep (REM); however, the neural mechanisms underlying the process are not fully known. Here, we investigated the role of the basolateral nuclei of the amygdala (BLA) in regulating the effects of stressful experience on sleep. We used optogenetics to briefly inhibit glutamatergic cells in BLA during the presentation of inescapable footshock (IS) and assessed effects on sleep, the acute stress response, and fear memory. c-Fos expression was also assessed in the amygdala and the medial prefrontal cortex (mPFC), both regions involved in coping with stress, and in brain stem regions implicated in the regulation of REM. Compared to control mice, peri-shock inhibition of BLA attenuated an immediate reduction in REM after IS and produced a significant overall increase in REM. Moreover, upon exposure to the shock context alone, mice receiving peri-shock inhibition of BLA during training showed increased REM without altered freezing (an index of fear memory) or stress-induced hyperthermia (an index of acute stress response). Inhibition of BLA during REM under freely sleeping conditions enhanced REM only when body temperature was high, suggesting the effect was influenced by stress. Peri-shock inhibition of BLA also led to elevated c-Fos expression in the central nucleus of the amygdala and mPFC and differentially altered c-Fos activity in the selected brain stem regions. Glutamatergic cells in BLA can modulate the effects of stress on REM and can mediate effects of fear memory on sleep that can be independent of behavioral fear. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  2. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Hoffman, Ann N; Lorson, Nickolaus G; Sanabria, Federico; Foster Olive, M; Conrad, Cheryl D

    2014-07-01

    Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6 h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Oxytocin reduces amygdala activity, increases social interactions, and reduces anxiety-like behavior irrespective of NMDAR antagonism.

    Science.gov (United States)

    Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E; Siegel, Steven J

    2015-08-01

    Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference. (c) 2015 APA, all rights reserved).

  4. Hypofunction of prefrontal cortex NMDA receptors does not change stress-induced release of dopamine and noradrenaline in amygdala but disrupts aversive memory.

    Science.gov (United States)

    Del Arco, Alberto; Ronzoni, Giacomo; Mora, Francisco

    2015-07-01

    A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia. The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event. Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory. Acute stress increased amygdala dialysate concentrations of dopamine (160% of baseline), noradrenaline (145% of baseline) and corticosterone (170% of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test. These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.

  5. Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats.

    Science.gov (United States)

    Dos Santos, Tiago Marcon; Kolling, Janaína; Siebert, Cassiana; Biasibetti, Helena; Bertó, Carolina Gessinger; Grun, Lucas Kich; Dalmaz, Carla; Barbé-Tuana, Florencia María; Wyse, Angela T S

    2017-02-01

    Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na + , K + -ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed). The animals were subjected to controlled exercise treadmill for 20min,three times a week, for two months prior to submission to the CVS (40days). Results show that CVS impaired performance in inhibitory avoidance at 24h and 7days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na + , K + -ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  6. CORTICOTROPIN-RELEASING HORMONE MICROINFUSION IN THE CENTRAL AMYGDALA DIMINISHES A CARDIAC PARASYMPATHETIC OUTFLOW UNDER STRESS-FREE CONDITIONS

    NARCIS (Netherlands)

    WIERSMA, A; BOHUS, B; KOOLHAAS, JM

    1993-01-01

    The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of

  7. How acute stress may enhance subsequent memory for threat stimuli outside the focus of attention: DLPFC-amygdala decoupling.

    Science.gov (United States)

    Luo, Yu; Fernández, Guillén; Hermans, Erno; Vogel, Susanne; Zhang, Yu; Li, Hong; Klumpers, Floris

    2018-05-01

    Stress-related disorders, e.g., anxiety and depression, are characterized by decreased top-down control for distracting information, as well as a memory bias for threatening information. However, it is unclear how acute stress biases mnemonic encoding and leads to prioritized storage of threat-related information even if outside the focus of attention. In the current study, healthy adults (N = 53, all male) were randomly assigned to stress induction using the socially evaluated cold-pressor test (SECPT) or a control condition. Participants performed a task in which they were required to identify a target letter within a string of letters that were either identical to the target and thereby facilitating detection (low distractor load) or mixed with other letters to complicate the search (high load). Either a fearful or neutral face was presented on the background, outside the focus of attention. Twenty-four hours later, participants were asked to perform a surprise recognition memory test for those background faces. Stress induction resulted in increased cortisol and negative subjective mood ratings. Stress did not affect visual search performance, however, participants in the stress group showed stronger memory compared to the control group for fearful faces in the low attentional load condition. Critically, the stress induced memory bias was accompanied by decoupling between amygdala and DLFPC during encoding, which may represent a mechanism for decreased ability to filter task-irrelevant threatening background information. The current study provides a potential neural account for how stress can produce a negative memory bias for threatening information even if presented outside the focus of attention. Despite of an adaptive advantage for survival, such tendencies may ultimately also lead to generalized fear, a possibility requiring additional investigation. Copyright © 2018. Published by Elsevier Inc.

  8. 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.

  9. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  10. Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala.

    Science.gov (United States)

    Suvrathan, Aparna; Bennur, Sharath; Ghosh, Supriya; Tomar, Anupratap; Anilkumar, Shobha; Chattarji, Sumantra

    2014-01-05

    Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of 'silent synapses', containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

  11. The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes.

    Science.gov (United States)

    Nicholson, Andrew A; Densmore, Maria; Frewen, Paul A; Théberge, Jean; Neufeld, Richard Wj; McKinnon, Margaret C; Lanius, Ruth A

    2015-09-01

    Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared with controls. Here we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioral symptoms. PTSD patients (n=49) with (n=13) and without (n=36) the dissociative subtype and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared with the PTSD-DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception-implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.

  12. Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala.

    Science.gov (United States)

    Krishnan, Balaji; Scott, Michael T; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia

    2016-02-01

    Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. Published by Elsevier Inc.

  13. Neurofascin Knock Down in the Basolateral Amygdala Mediates Resilience of Memory and Plasticity in the Dorsal Dentate Gyrus Under Stress.

    Science.gov (United States)

    Saha, Rinki; Kriebel, Martin; Volkmer, Hansjürgen; Richter-Levin, Gal; Albrecht, Anne

    2018-02-05

    Activation of the amygdala is one of the hallmarks of acute stress reactions and a central element of the negative impact of stress on hippocampus-dependent memory and cognition. Stress-induced psychopathologies, such as posttraumatic stress disorder, exhibit a sustained hyperactivity of the amygdala, triggered at least in part by deficits in GABAergic inhibition that lead to shifts in amygdalo-hippocampal interaction. Here, we have utilized lentiviral knock down of neurofascin to reduce GABAergic inhibition specifically at the axon initial segment (AIS) of principal neurons within the basolateral amygdala (BLA) of rats. Metaplastic effects of such a BLA modulation on hippocampal synaptic function were assessed using BLA priming prior to the induction of long-term potentiation (LTP) on dentate gyrus synapses in anesthetized rats in vivo. The knock down of neurofascin in the BLA prevented a priming-induced impairment on LTP maintenance in the dentate gyrus. At the behavioral level, a similar effect was observable, with neurofascin knock down preventing the detrimental impact of acute traumatic stress on hippocampus-dependent spatial memory retrieval in a water maze task. These findings suggest that reducing GABAergic inhibition specifically at the AIS synapses of the BLA alters amygdalo-hippocampal interactions such that it attenuates the adverse impact of acute stress exposure on cognition-related hippocampal functions.

  14. Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation.

    Science.gov (United States)

    Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; Fornari, Raquel V; Roozendaal, Benno

    2015-05-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.

  15. Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Bender, C L; Otamendi, A; Calfa, G D; Molina, V A

    2018-04-20

    Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

    Science.gov (United States)

    Wilson, Marlene A.; Grillo, Claudia A.; Fadel, Jim R.; Reagan, Lawrence P.

    2015-01-01

    Neuroplasticity may be defined as the ability of the central nervous system (CNS) to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD) and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior. PMID:26844236

  17. Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

    Directory of Open Access Journals (Sweden)

    Marlene A. Wilson

    2015-01-01

    Full Text Available Neuroplasticity may be defined as the ability of the central nervous system (CNS to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior.

  18. The aqueous extract of Albizia adianthifolia leaves attenuates 6-hydroxydopamine-induced anxiety, depression and oxidative stress in rat amygdala.

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    Beppe, Galba Jean; Dongmo, Alain Bertrand; Foyet, Harquin Simplice; Dimo, Théophile; Mihasan, Marius; Hritcu, Lucian

    2015-10-19

    While the Albizia adianthifolia (Schumach.) W. Wright (Fabaceae) is a traditional herb largely used in the African traditional medicine as analgesic, purgative, antiinflammatory, antioxidant, antimicrobial, memory-enhancer, anxiolytic and antidepressant drug, there are no scientific data that clarify the anxiolytic and antidepressant-like effects in 6-hydroxydopamine (6-OHDA)-lesioned animal model of Parkinson's disease. This study was undertaken in order to identify the effects of aqueous extract of A. adianthifolia leaves on 6-hydroxydopamine-induced anxiety, depression and oxidative stress in the rat amygdala. The effect of the aqueous extract of A. adianthifolia leaves (150 and 300 mg/kg, orally, daily, for 21 days) on anxiety and depression was assessed using elevated plus-maze and forced swimming tests, as animal models of anxiety and depression. Also, the antioxidant activity in the rat amygdala was assessed using assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Statistical analyses were performed using by one-way analysis of variance (ANOVA). Significant differences were determined by Tukey's post hoc test. F values for which p amygdala. Our results suggest that the aqueous extract ameliorates 6-OHDA-induced anxiety and depression by attenuation of the oxidative stress in the rat amygdala. These pieces of evidence accentuate its use in traditional medicine.

  19. Memory-enhancing corticosterone treatment increases amygdala norepinephrine and Arc protein expression in hippocampal synaptic fractions

    NARCIS (Netherlands)

    McReynolds, Jayme R.; Donowho, Kyle; Abdi, Amin; McGaugh, James L.; Roozendaal, Benno; McIntyre, Christa K.

    Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of memory for emotionally arousing events through interactions with the noradrenergic system of the basolateral complex of the amygdala (BLA). We previously reported that intra-BLA administration of a

  20. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

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    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

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    Mouna Maroun

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  2. Role of basal stress hormones and amygdala dimensions in stress coping strategies of male rhesus monkeys in response to a hazard-reward conflict

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    Elaheh Tekieh

    2017-08-01

    Full Text Available Objective(s: In the present study the effect of stress on monkeys that had learned to retrieve food from a five-chamber receptacle, as well as the relationship between their behavior and the serum cortisol and epinephrine levels and relative size of the amygdala was evaluated. Materials and Methods: Six male rhesus monkeys were individually given access to the food reward orderly. They could easily retrieve the rewards from all chambers except for the chamber 4, which a brief, mild electric shock (3 V was delivered to them upon touching the chamber’s interior. The coping behaviors were video-recorded and analyzed offline. Baseline serum cortisol and epinephrine levels were measured before the experiments using monkey enzyme-linked immunosorbent assay kit. One week after the behavioral experiment, the monkeys’ brains were scanned using magnetic resonance imaging under general anesthesia. The cross-sectional area of the left amygdala in sagittal plane relative to the area of the whole brain in the same slice was evaluated by the planimetric method using ImageJ software. Results: Exposure to the distressing condition caused different behavioral responses. Monkeys with higher baseline levels of serum cortisol and epinephrine and larger amygdala behaved more violently in the face of stress, indicating adopting emotion-focused stress-coping strategies. Conversely, those with low plasma epinephrine, moderate cortisol, and smaller amygdala showed perseverative behavior, indicating a problem-focused coping style. Conclusion: In dealing with the same stress, different responses might be observed from nonhuman primates according to their cortisol and epinephrine levels as well as their amygdala dimensions.

  3. Acute physical and psychological stress effects on visceral hypersensitivity in male rat: role of central nucleus of the amygdala

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    Hamideh Afzali

    2017-04-01

    Full Text Available Objective: The aim of this study was to investigate the effects of acute physical and psychological stress and temporary central nucleus of the amygdala (CeA block on stress-induced visceral hypersensitivity. Methods: Forty two male Wistar rats were used in this study. Animals were divided into 7 groups (n = 6; 1 – Control, 2 – physical stress, 3 – psychological stress, 4 – sham, 5 – lidocaine, 6 – lidocaine + physical stress and 7 – lidocaine + psychological stress. Stress induction was done using a communication box. Results: Abdominal withdrawal reflex (AWR score was monitored one hour after stress exposure. AWR score significantly heightened at 20, 40 and 60 mmHg in the psychological stress group compared with control (p < 0.05, while, it was almost unchanged in other groups. This score was strikingly decreased at 20, 40 and 60 mmHg in lidocaine + psychological stress group compared with psychological stress with no tangible response on physical stress. Total stool weight was significantly increased in psychological stress group compared with control (0.72 ± 0.15, 0.1 ± 0.06 g (p < 0.05, but it did not change in physical stress compared to control group (0.16 ± 0.12, 0.1 ± 0.06 g (p < 0.05. Concomitant use of lidocaine with stress followed the same results in psychological groups (0.18 ± 0.2, 0.72 ± 0.15 g (p < 0.05, while it did not have any effect on physical stress group (0.25 ± 0.1, 0.16 ± 0.12 g (p < 0.05. Conclusions: Psychological stress could strongly affect visceral hypersensitivity. This effect is statistically comparable with physical stress. Temporary CeA block could also reduce visceral hypersensitivity post-acute psychological stress. Resumen: Objetivo: O objetivo desse estudo foi investigar os efeitos do estresse físico e psicológico agudo e bloqueio temporário do núcleo central da amídala (CeA na hipersensibilidade visceral induzida por estresse. M

  4. Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors

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    Evren Eraslan

    2015-01-01

    Full Text Available Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON, acute noise exposure (ANE, and chronic noise exposure (CNE. The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR. The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

  5. Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors.

    Science.gov (United States)

    Eraslan, Evren; Akyazi, Ibrahim; Erg L-Ekiz, Elif; Matur, Erdal

    2015-01-01

    Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

  6. Testosterone administration in women increases amygdala responses to fearful and happy faces

    NARCIS (Netherlands)

    Bos, P.A.; Honk, J. van; Ramsey, N.F.; Stein, D.J.; Hermans, E.J.

    2013-01-01

    Data from both rodents and humans show that testosterone reduces fear. This effect is hypothesized to result from testosterone's down regulating effects on the amygdala, a key region in the detection of threat and instigator of fight-or-flight behavior. However, neuroimaging studies employing

  7. Testosterone increases amygdala reactivity in middle-aged women to a young adulthood level.

    NARCIS (Netherlands)

    Wingen, G.A. van; Zylicz, S.A.; Pieters, S.; Mattern, C.; Verkes, R.J.; Buitelaar, J.K.; Fernandez, G.S.E.

    2009-01-01

    Testosterone modulates mood and sexual function in women. However, androgen levels decline with age, which may relate to the age-associated change in sexual functioning and the prevalence of mood and anxiety disorders. These effects of testosterone are potentially mediated by the amygdala. In the

  8. Testosterone increases amygdala reactivity in middle-aged women to a young adulthood level

    NARCIS (Netherlands)

    van Wingen, Guido A.; Zylicz, Staś A.; Pieters, Sara; Mattern, Claudia; Verkes, Robbert Jan; Buitelaar, Jan K.; Fernández, Guillén

    2009-01-01

    Testosterone modulates mood and sexual function in women. However, androgen levels decline with age, which may relate to the age-associated change in sexual functioning and the prevalence of mood and anxiety disorders. These effects of testosterone are potentially mediated by the amygdala. In the

  9. Job stress and productivity increase.

    Science.gov (United States)

    Adaramola, Samson Sunday

    2012-01-01

    This paper examines mental and physical pressures that workers bear at work. The authors discuss how on the-job stress affects a person's capabilities and productivity, and how such pressures lend to higher incidences of accidents at work. The paper also discuss methods of reducing job-related stress and increasing productivity. An intervention was conducted amongst workers in a private firm. It shows mental and emotional pressure can affect performance and productivity of a worker on the job. One of the biggest influences of today's worker is on the-job stress. Job stress occurs when the requirements of the job do not match the capabilities, resources, or needs of the worker. This consequently affects how a person would normally deal with customer service problems, grievances, violence, conflict, and decisions on the job. Stress is an inevitable part of everyday life, and is therefore a distinct part of a person's job. To properly control the outcome of stress, there are certain precautions and methods that should be taken that will boost productivity.

  10. Unsatisfied relatedness, not competence or autonomy, increases trait anger through the right amygdala.

    Science.gov (United States)

    Wang, Yinan; Kong, Feng; Kong, Xiangzhen; Zhao, Yuanfang; Lin, Danhua; Liu, Jia

    2017-10-01

    Anger is a common negative emotion in social life. Behavioral research suggests that unsatisfied relatedness, autonomy, and competence are related to anger. However, it remains unclear whether these unsatisfied needs all contribute to anger or just a particular unsatisfied need is the main source of anger. In addition, little is known about the neural substrate between unsatisfied needs and anger. To address these two questions, we used voxel-based morphometry (VBM) to explore the neural substrate underlying the relation between unsatisfied needs and trait anger. Behaviorally, we found that although all three unsatisfied needs were correlated with trait anger, unsatisfied relatedness was the only factor that was uniquely related to trait anger. Neurally, the gray matter volume of the right amygdala was correlated with trait anger, which fits nicely with the role of the amygdala as a core region for processing anger. Importantly, the right amygdala mediated the total effect of unsatisfied relatedness on trait anger, even after controlling for general personality dispositions. Our results contribute to the theoretical conceptualization of anger by elucidating the unique role of unsatisfied relatedness in anger and the neural substrate underlying such relation.

  11. Disorganized Attachment in Infancy Predicts Greater Amygdala Volume in Adulthood

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    Lyons-Ruth, K.; Pechtel, P.; Yoon, S.A.; Anderson, C.M.; Teicher, M.H.

    2016-01-01

    Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans, the amygdala develops rapidly during the first two years of life. Thus, disturbed care during this period may be particularly important to amygdala development. In the context of a 30-year longitudinal study of impoverished, highly stressed families, we assessed whether disorganization of the attachment relationship in infancy was related to amygdala volume in adulthood. Amygdala volumes were assessed among 18 low-income young adults (8M/10F, 29.33±0.49 years) first observed in infancy (8.5±5.6 months) and followed longitudinally to age 29. In infancy (18.58±1.02 mos), both disorganized infant attachment behavior and disrupted maternal communication were assessed in the standard Strange Situation Procedure (SSP). Increased left amygdala volume in adulthood was associated with both maternal and infant components of disorganized attachment interactions at 18 months of age (overall r = .679, p attachment disturbance in adolescence, were not significantly related to left amygdala volume. Left amygdala volume was further associated with dissociation and limbic irritability in adulthood. Finally, left amygdala volume mediated the prediction from attachment disturbance in infancy to limbic irritability in adulthood. Results point to the likely importance of quality of early care for amygdala development in human children as well as in rodents. The long-term prediction found here suggests that the first two years of life may be an early sensitive period for amygdala development during which clinical intervention could have particularly important consequences for later child outcomes. PMID:27060720

  12. Amygdala activation and GABAergic gene expression in hippocampal sub-regions at the interplay of stress and spatial learning

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    Osnat eHadad-Ophir

    2014-01-01

    Full Text Available Molecular processes in GABAergic local circuit neurons critically contribute to information processing in the hippocampus and to stress-induced activation of the amygdala. In the current study, we determined expression changes in GABA-related factors induced in subregions of the dorsal hippocampus as well as in the BLA of rats 5h after spatial learning in a Morris Water maze, using laser microdissection and quantitative real-time PCR. Spatial learning resulted in highly selective pattern of changes in hippocampal subregions: gene expression levels of neuropeptide Y were reduced in the hilus of the dentate gyrus, whereas somatostatin was increased in the stratum oriens of CA3. The GABA-synthesizing enzymes GAD65 and GAD67 as well as the neuropeptide cholecystokinin were reduced in stratum oriens of CA1. In the BLA, expression of GAD65 and GAD67 were reduced compared to a handled Control group. These expression patterns were further compared to alterations in a group of rats that have been exposed to the water maze but were not provided with an invisible escape platform. In this Water Exposure group, no expression changes were observed in any of the hippocampal subregions, but a differential regulation of all selected target genes was evident in the BLA. These findings suggest that expression changes of GABAergic factors in the hippocampus are associated with spatial learning, while additional stress effects modulate expression alterations in the BLA. Indeed, while in both experimental groups plasma corticosterone levels were enhanced, only Water Exposure stress activated the basolateral amygdala, as indicated by increased levels of phosphorylated ERK1/2. Altered GABAergic function in the BLA may thus contribute to memory consolidation in the hippocampus, in relation to levels of stress and emotionality associated with the experience.

  13. Neural responses to threat and reward interact to predict stress-related problem drinking: A novel protective role of the amygdala

    Science.gov (United States)

    2012-01-01

    Background Research into neural mechanisms of drug abuse risk has focused on the role of dysfunction in neural circuits for reward. In contrast, few studies have examined the role of dysfunction in neural circuits of threat in mediating drug abuse risk. Although typically regarded as a risk factor for mood and anxiety disorders, threat-related amygdala reactivity may serve as a protective factor against substance use disorders, particularly in individuals with exaggerated responsiveness to reward. Findings We used well-established neuroimaging paradigms to probe threat-related amygdala and reward-related ventral striatum reactivity in a sample of 200 young adult students from the ongoing Duke Neurogenetics Study. Recent life stress and problem drinking were assessed using self-report. We found a significant three-way interaction between threat-related amygdala reactivity, reward-related ventral striatum reactivity, and recent stress, wherein individuals with higher reward-related ventral striatum reactivity exhibit higher levels of problem drinking in the context of stress, but only if they also have lower threat-related amygdala reactivity. This three-way interaction predicted both contemporaneous problem drinking and problem drinking reported three-months later in a subset of participants. Conclusions These findings suggest complex interactions between stress and neural responsiveness to both threat and reward mediate problem drinking. Furthermore, they highlight a novel protective role for threat-related amygdala reactivity against drug use in individuals with high neural reactivity to reward. PMID:23151390

  14. Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.

    Science.gov (United States)

    Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael D

    2016-02-01

    Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.

  15. Chemosensory function of the amygdala.

    Science.gov (United States)

    Gutiérrez-Castellanos, Nicolás; Martínez-Marcos, Alino; Martínez-García, Fernando; Lanuza, Enrique

    2010-01-01

    The chemosensory amygdala has been traditionally divided into two divisions based on inputs from the main (olfactory amygdala) or accessory (vomeronasal amygdala) olfactory bulbs, supposedly playing different and independent functional roles detecting odors and pheromones, respectively. Recently, there has been increased anatomical evidence of convergence inputs from the main and accessory bulbs in some areas of the amygdala, and this is correlated with functional evidence of interrelationships between the olfactory and the vomeronasal systems. This has lead to the characterization of a third division of the chemosensory amygdala, the mixed chemosensory amygdala, providing a new perspective of how chemosensory information is processed in the amygdaloid complex, in particular in relation to emotional behaviors. In this chapter, we analyze the anatomical and functional organization of the chemosensory amygdala from this new perspective. Finally, the evolutionary changes of the chemosensory nuclei of the mammalian amygdala are discussed, paying special attention to the case of primates, including humans. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Genetic Deletion of Neuronal PPARγ Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPARγ Function.

    Science.gov (United States)

    Domi, Esi; Uhrig, Stefanie; Soverchia, Laura; Spanagel, Rainer; Hansson, Anita C; Barbier, Estelle; Heilig, Markus; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-12-14

    attention for its involvement in the regulation of CNS immune response and functions. Here, we demonstrate that neuronal PPARγ activation prevented the negative emotional effects of stress and exerted anxiolytic actions without influencing hypothalamic-pituitary-adrenal axis function. Conversely, pharmacological blockade or genetic deletion of PPARγ enhanced anxiogenic responses and increased vulnerability to stress. These effects appear to be controlled by PPARγ neuronal-mediated mechanisms in the amygdala. Copyright © 2016 the authors 0270-6474/16/3612612-13$15.00/0.

  17. Disrupted amygdala-prefrontal connectivity during emotion regulation links stress-reactive rumination and adolescent depressive symptoms

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    Carina H. Fowler

    2017-10-01

    Full Text Available Rumination in response to stress (stress-reactive rumination has been linked to higher levels of depressive symptoms in adolescents. However, no work to date has examined the neural mechanisms connecting stress-reactive rumination and adolescent depressive symptoms. The present work attempted to bridge this gap through an fMRI study of 41 adolescent girls (Mage = 15.42, SD = 0.33 – a population in whom elevated levels of depressive symptoms, rumination, and social stress sensitivity are displayed. During the scan, participants completed two tasks: an emotion regulation task and a social stress task. Using psychophysiological interaction (PPI analyses, we found that positive functional connectivity between the amygdala and ventrolateral prefrontal cortex (VLPFC during the emotion regulation task mediated the association between stress-reactive rumination and depressive symptoms. These results suggest that stress-reactive rumination may interfere with the expression and development of neural connectivity patterns associated with effective emotion regulation, which may contribute, in turn, to heightened depressive symptoms.

  18. [Hormonal homeostasis and intraocular pressure in chronic emotional stress caused by influences acting on the amygdala].

    Science.gov (United States)

    Isakova, L S; Danilov, G E; Egorkina, S B; Butolin, E G

    1989-01-01

    Changes in intraocular pressure, eye hydrodynamics and the amount of hypophyseal, thyroid, adrenal and pancreatic hormones were studied during continuous stimulation of amygdaloid complex or after administration of angiotensin II into the structure in rabbits. The effects involved changes in hormonal homeostasis and elevation of intraocular pressure due to a hypersecretion of intraocular fluid. The administration of angiotensin II during the amygdala stimulation enhanced the changes.

  19. Hypertensive response to stress: the role of histaminergic H1 and H2 receptors in the medial amygdala.

    Science.gov (United States)

    de Almeida, Daniela Oliveira; Ferreira, Hilda Silva; Pereira, Luana Bomfim; Fregoneze, Josmara Bartolomei

    2015-05-15

    Different brain areas seem to be involved in the cardiovascular responses to stress. The medial amygdala (MeA) has been shown to participate in cardiovascular control, and acute stress activates the MeA to a greater extent than any of the other amygdaloid structures. It has been demonstrated that the brain histaminergic system may be involved in behavioral, autonomic and neuroendocrine responses to stressful situations. The aim of the present study was to investigate the role of the histaminergic receptors H1 and H2 in cardiovascular responses to acute restraint stress. Wistar rats (280-320g) received bilateral injections of cimetidine, mepyramine or saline into the MeA and were submitted to 45min of restraint stress. Mepyramine microinjections at doses of 200, 100 and 50nmol promoted a dose-dependent blockade of the hypertensive response induced by the restraint stress. Cimetidine (200 and 100nmol) promoted a partial blockade of the hypertensive response to stress only at the highest dose administered. Neither drugs altered the typical stress-evoked tachycardiac responses. Furthermore, mepyramine and cimetidine were unable to modify the mean arterial pressure or heart rate of freely moving rats under basal conditions (non-stressed rats). The data suggest that in the MeA the histaminergic H1 receptors appear to be more important than H2 receptors in the hypertensive response to stress. Furthermore, there appears to be no histaminergic tonus in the MeA controlling blood pressure during non-stress conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Relation between Amygdala Structure and Function in Adolescents with Bipolar Disorder

    Science.gov (United States)

    Kalmar, Jessica H.; Wang, Fei; Chepenik, Lara G.; Womer, Fay Y.; Jones, Monique M.; Pittman, Brian; Shah, Maulik P.; Martin, Andres; Constable, R. Todd; Blumberg, Hilary P.

    2009-01-01

    Adolescents with bipolar disorder showed decreased amygdala volume and increased amygdala response to emotional faces. Amygdala volume is inversely related to activation during emotional face processing.

  1. Rapid corticosteroid actions on synaptic plasticity in the mouse basolateral amygdala: relevance of recent stress history and β-adrenergic signaling.

    Science.gov (United States)

    Sarabdjitsingh, R A; Joëls, M

    2014-07-01

    The rodent stress hormone corticosterone rapidly enhances long-term potentiation in the CA1 hippocampal area, but leads to a suppression when acting in a more delayed fashion. Both actions are thought to contribute to stress effects on emotional memory. Emotional memory formation also involves the basolateral amygdala, an important target area for corticosteroid actions. We here (1) investigated the rapid effects of corticosterone on amygdalar synaptic potentiation, (2) determined to what extent these effects depend on the mouse's recent stress history or (3) on prior β-adrenoceptor activation; earlier studies at the single cell level showed that especially a recent history of stress changes the responsiveness of basolateral amygdala neurons to corticosterone. We report that, unlike the hippocampus, stress enhances amygdalar synaptic potentiation in a slow manner. In vitro exposure to 100 nM corticosterone quickly decreases synaptic potentiation, and causes only transient potentiation in tissue from stressed mice. This transient type of potentiation is also seen when β-adrenoceptors are blocked during stress and this is further exacerbated by subsequent in vitro administered corticosterone. We conclude that stress and corticosterone change synaptic potentiation in the basolateral amygdala in a manner opposite to that seen in the hippocampus and that renewed exposure to corticosterone only allows induction of non-persistent forms of synaptic potentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

    NARCIS (Netherlands)

    Ronzoni, G.; Arco, A. Del; Mora, F.; Segovia, G.

    2016-01-01

    Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats

  3. MicroRNA-19b associates with Ago2 in the amygdala following chronic stress and regulates the adrenergic receptor beta 1.

    Science.gov (United States)

    Volk, Naama; Paul, Evan D; Haramati, Sharon; Eitan, Chen; Fields, Brandon K K; Zwang, Raaya; Gil, Shosh; Lowry, Christopher A; Chen, Alon

    2014-11-05

    Activation of the stress response in the presence of diverse challenges requires numerous adaptive molecular and cellular changes. To identify specific microRNA molecules that are altered following chronic stress, mice were subjected to the chronic social defeat procedure. The amygdala from these mice was collected and a screen for microRNAs that were recruited to the RNA-induced silencing complex and differentially expressed between the stressed and unstressed mice was conducted. One of the microRNAs that were significantly altered was microRNA-19b (miR-19b). Bioinformatics analysis revealed the adrenergic receptor β-1 (Adrb1) as a potential target for this microRNA with multiple conserved seed sites. Consistent with its putative regulation by miR-19b, Adrb1 levels were reduced in the basolateral amygdala (BLA) following chronic stress. In vitro studies using luciferase assays showed a direct effect of miR-19b on Adrb1 levels, which were not evident when miR-19b seed sequences at the Adrb1 transcript were mutated. To assess the role of miR-19b in memory stabilization, previously attributed to BLA-Adrb1, we constructed lentiviruses designed to overexpress or knockdown miR-19b. Interestingly, adult mice injected bilaterally with miR-19b into the BLA showed lower freezing time relative to control in the cue fear conditioning test, and deregulation of noradrenergic circuits, consistent with downregulation of Adrb1 levels. Knockdown of endogenous BLA-miR-19b levels resulted in opposite behavioral and noradrenergic profile with higher freezing time and increase 3-methoxy-4-hydroxyphenylglycol/noradrenaline ratio. These findings suggest a key role for miR-19b in modulating behavioral responses to chronic stress and Adrb1 as an important target of miR-19b in stress-linked brain regions. Copyright © 2014 the authors 0270-6474/14/3415070-13$15.00/0.

  4. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

    Science.gov (United States)

    Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

    2017-04-01

    Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.

  5. Growth hormone biases amygdala network activation after fear learning.

    Science.gov (United States)

    Gisabella, B; Farah, S; Peng, X; Burgos-Robles, A; Lim, S H; Goosens, K A

    2016-11-29

    Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the 'over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the process by which neurons compete to encode memories, to favor neurons that have stronger inputs. Viral overexpression of GH in the amygdala increased the number of amygdala cells activated by fear memory formation. GH-overexpressing cells were especially biased to express the immediate early gene c-Fos after fear conditioning, revealing strong autocrine actions of GH in the amygdala. In addition, we observed dramatically enhanced dendritic spine density in GH-overexpressing neurons. These data elucidate a previously unrecognized autocrine role for GH in the regulation of amygdala neuron function and identify specific mechanisms by which chronic stress, by enhancing GH in the amygdala, may predispose an individual to excessive fear memory formation.

  6. Fluoxetine reverts chronic restraint stress-induced depression-like behaviour and increases neuropeptide Y and galanin expression in mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Wörtwein, Gitta

    2011-01-01

    Stressful life events and chronic stress are implicated in the development of depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown to modulate the stress response, and exert antidepressant-like effects in rodents. To further investigate these neuropeptides in depression......-like behaviour, NPY and galanin gene expression was studied in brains of mice subjected to chronic restraint stress (CRS) and concomitant treatment with the antidepressant fluoxetine (FLX). CRS caused a significant increase in depression-like behaviour that was associated with increased NPY mRNA levels...... in the medial amygdala. Concomitant FLX treatment reverted depression-like effects of CRS and led to significant increases in levels of NPY and galanin mRNA in the dentate gyrus, amygdala, and piriform cortex. These findings suggest that effects on NPY and galanin gene expression could play a role...

  7. Serotonin transporter genotype (5-HTTLPR): effects of neutral and undefined conditions on amygdala activation.

    Science.gov (United States)

    Heinz, Andreas; Smolka, Michael N; Braus, Dieter F; Wrase, Jana; Beck, Anne; Flor, Herta; Mann, Karl; Schumann, Gunter; Büchel, Christian; Hariri, Ahmad R; Weinberger, Daniel R

    2007-04-15

    A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. Functional imaging studies show that during the presentation of aversive versus neutral cues, healthy carriers of the short (s) allele showed stronger amygdala activation than long (l) carriers. However, a recent report suggested that this interaction is driven by amygdala deactivation during presentation of neutral stimuli in s carriers. Functional MRI was used to assess amygdala activation during the presentation of a fixation cross or affectively aversive or neutral visual stimuli in 29 healthy men. Amygdala activation was increased in s carriers during undefined states such as the presentation of a fixation cross compared with emotionally neutral conditions. This finding suggests that s carriers show stronger amygdala reactivity to stimuli and contexts that are relatively uncertain, which we propose are stressful.

  8. Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress-induced amnesia.

    Science.gov (United States)

    Zoladz, Phillip R; Park, Collin R; Halonen, Joshua D; Salim, Samina; Alzoubi, Karem H; Srivareerat, Marisa; Fleshner, Monika; Alkadhi, Karim A; Diamond, David M

    2012-03-01

    We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing. Copyright © 2011 Wiley Periodicals, Inc.

  9. FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats.

    Science.gov (United States)

    Xu, Jingjing; Wang, Rui; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2017-12-01

    Exposure to stressful events induces depressive-like symptoms and increases susceptibility to depression. However, the molecular mechanisms are not fully understood. Studies reported that FK506 binding protein51 (FKBP5), the co-chaperone protein of glucocorticoid receptors (GR), plays a crucial role. Further, miR-124a and miR-18a are involved in the regulation of FKBP5/GR function. However, few studies have referred to effects of early life stress on depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a in the basolateral amygdala (BLA) from adolescence to adulthood. This study aimed to examine the dynamic alternations of depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a expressions in the BLA of chronic unpredictable mild stress (CUMS) rats and dexamethasone administration rats during the adolescent period. Meanwhile, the GR antagonist, RU486, was used as a means of intervention. We found that CUMS and dexamethasone administration in the adolescent period induced permanent depressive-like behaviours and memory impairment, decreased GR expression, and increased FKBP5 and miR-124a expression in the BLA of both adolescent and adult rats. However, increased miR-18a expression in the BLA was found only in adolescent rats. Depressive-like behaviours were positively correlated with the level of miR-124a, whereas GR levels were negatively correlated with those in both adolescent and adult rats. Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Glucocorticoid receptors in the basolateral amygdala mediated the restraint stress-induced reinstatement of methamphetamine-seeking behaviors in rats.

    Science.gov (United States)

    Taslimi, Zahra; Sarihi, Abdolrahman; Haghparast, Abbas

    2018-04-21

    Methamphetamine (METH) addiction is a growing epidemic worldwide. It is a common psychiatric disease and stress has an important role in the drug seeking and relapse behaviors. The involvement of the basolateral amygdala (BLA) in effects of stress on the reward pathway has been discussed in several studies. In this study, we tried to find out the involvement of glucocorticoid receptors (GRs) in the BLA in stress-induced reinstatement of the extinguished METH-induced conditioned place preference (CPP) in rats. The CPP paradigm was done in eighty-one adult male Wistar rats weighing 220-250 g. The animals received a daily injection of methamphetamine (0.5 mg/kg), during the conditioning phase. In extinction phase, the rats were put in the CPP box for 30 min per day for 8 days. After the extinction, the animals were exposed to acute restraint stress (ARS), 3 h before subcutaneous administration of sub-threshold dose of methamphetamine (0.125 mg/kg), based on our previous study, in reinstatement phase. In separated groups, the rats were exposed to chronic restraint stress (CRS) for 1 h each day during the extinction phase. To block the GRs in BLA, the animals unilaterally received RU38486 as GRs antagonist (10, 30 and 90 ng/0.3 μl DMSO) in all ARS groups on reinstatement day. In separated experiments, RU38486 (3, 10 and 30 ng/0.3 μl DMSO) was microinjected into the BLA in CRS groups prior to exposure to stress every day in extinction phase. The results revealed that intra-BLA RU38486 in ARS (90 ng) and CRS (10 and 30 ng) groups significantly prevented the stress-induced reinstatement. It can be proposed that stress partially exerts its effect on the reward pathway via GRs in the BLA. This effect was not quite similar in acute and chronic stress conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI

    Science.gov (United States)

    Brashers-Krug, Tom; Jorge, Ricardo

    2015-01-01

    Objectives Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC) in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent. Methods We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI) session to 50 veterans of recent combat. We collected skin conductance responses (SCRs) as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD) signal in the amygdala and ACC to symptom measures and to SCRs. Results Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala. Conclusions Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The

  12. Stress history increases alcohol intake in relapse: relation to phosphodiesterase 10A.

    Science.gov (United States)

    Logrip, Marian L; Zorrilla, Eric P

    2012-09-01

    Stressful experiences can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock (stress history) or light cues alone (control) prior to acquisition of alcohol self-administration (1-hour sessions, fixed ratio 1-3, 100 µl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a twofold elevation in alcohol self-administration, as compared with low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate and cyclic guanosine monophosphate hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low-drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals. © 2012 The Authors. Addiction Biology © 2012 Society for the Study of Addiction.

  13. Stress hormones receptors in the amygdala mediate the effects of stress on the consolidation, but not the retrieval, of a non aversive spatial task.

    Directory of Open Access Journals (Sweden)

    Amir Segev

    Full Text Available This study examined the effects of the arousal level of the rat and exposure to a behavioral stressor on acquisition, consolidation and retrieval of a non-aversive hippocampal-dependent learning paradigm, the object location task. Learning was tested under two arousal conditions: no previous habituation to the experimental context (high novelty stress/arousal level or extensive prior habituation (reduced novelty stress/arousal level. Results indicated that in the habituated rats, exposure to an out-of-context stressor (i.e, elevated platform stress impaired consolidation and retrieval, but not acquisition, of the task. Non-habituated animals under both stressed and control conditions did not show retention of the task. In habituated rats, RU-486 (10 ng/side, a glucocorticoid receptor (GR antagonist, or propranolol (0.75 µg/side, a beta-adrenergic antagonist, injected into the basolateral amygdala (BLA, prevented the impairing effects of the stressor on consolidation, but not on retrieval. The CB1/CB2 receptor agonist WIN55,212-2 (WIN, 5 µg/side microinjected into the BLA did not prevent the effects of stress on either consolidation or retrieval. Taken together the results suggest that: (i GR and β-adrenergic receptors in the BLA mediate the impairing effects of stress on the consolidation, but not the retrieval, of a neutral, non-aversive hippocampal-dependent task, (ii the impairing effects of stress on hippocampal consolidation and retrieval are mediated by different neural mechanisms (i.e., different neurotransmitters or different brain areas, and (iii the effects of stress on memory depend on the interaction between several main factors such as the stage of memory processing under investigation, the animal's level of arousal and the nature of the task (neutral or aversive.

  14. Stress hormones receptors in the amygdala mediate the effects of stress on the consolidation, but not the retrieval, of a non aversive spatial task.

    Science.gov (United States)

    Segev, Amir; Ramot, Assaf; Akirav, Irit

    2012-01-01

    This study examined the effects of the arousal level of the rat and exposure to a behavioral stressor on acquisition, consolidation and retrieval of a non-aversive hippocampal-dependent learning paradigm, the object location task. Learning was tested under two arousal conditions: no previous habituation to the experimental context (high novelty stress/arousal level) or extensive prior habituation (reduced novelty stress/arousal level). Results indicated that in the habituated rats, exposure to an out-of-context stressor (i.e, elevated platform stress) impaired consolidation and retrieval, but not acquisition, of the task. Non-habituated animals under both stressed and control conditions did not show retention of the task. In habituated rats, RU-486 (10 ng/side), a glucocorticoid receptor (GR) antagonist, or propranolol (0.75 µg/side), a beta-adrenergic antagonist, injected into the basolateral amygdala (BLA), prevented the impairing effects of the stressor on consolidation, but not on retrieval. The CB1/CB2 receptor agonist WIN55,212-2 (WIN, 5 µg/side) microinjected into the BLA did not prevent the effects of stress on either consolidation or retrieval. Taken together the results suggest that: (i) GR and β-adrenergic receptors in the BLA mediate the impairing effects of stress on the consolidation, but not the retrieval, of a neutral, non-aversive hippocampal-dependent task, (ii) the impairing effects of stress on hippocampal consolidation and retrieval are mediated by different neural mechanisms (i.e., different neurotransmitters or different brain areas), and (iii) the effects of stress on memory depend on the interaction between several main factors such as the stage of memory processing under investigation, the animal's level of arousal and the nature of the task (neutral or aversive).

  15. Amygdala, Anxiety and Alpha(1) Adrenoceptors: Investigations Utilizing a Rodent Model of Traumatic Stress

    Science.gov (United States)

    2006-08-23

    the effect of a variety of different modifiers to the startle response, from drugs to environmental conditions . It has repeatedly been seen that...in rats. J. Neurosci. 1999;19: 8696-8703. Maren,S. Neurobiology of Pavlovian fear conditioning . Annu. Rev. Neurosci. 2001;24: 897-931. Marmar,CR...stress can result in post-traumatic stress disorder (PTSD) and other pathophysiological conditions . PTSD is characterized by a number of

  16. Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats.

    Science.gov (United States)

    Urakawa, Susumu; Takamoto, Kouich; Hori, Etsuro; Sakai, Natsuko; Ono, Taketoshi; Nishijo, Hisao

    2013-01-25

    Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior. Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test. Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the

  17. Behavioral Inhibition System activity is associated with increased amygdala and hippocampal gray matter volume: A voxel-based morphometry study.

    Science.gov (United States)

    Barrós-Loscertales, A; Meseguer, V; Sanjuán, A; Belloch, V; Parcet, M A; Torrubia, R; Avila, C

    2006-11-15

    Recent research has examined anxiety and hyperactivity in the amygdala and the anterior hippocampus while processing aversive stimuli. In order to determine whether these functional differences have a structural basis, optimized voxel-based morphometry was used to study the relationship between gray matter concentration in the brain and scores on a Behavioral Inhibition System measure (the Sensitivity to Punishment scale) in a sample of 63 male undergraduates. Results showed a positive correlation between Sensitivity to Punishment scores and gray matter volume in the amygdala and the hippocampal formation, that is, in areas that Gray, J.A., and McNaughton, N.J. (2000). The neuropsychology of anxiety. Oxford: Oxford Medical Publications. associated with the Behavioral Inhibition System.

  18. Individual Differences in Animal Stress Models: Considering Resilience, Vulnerability, and the Amygdala in Mediating the Effects of Stress and Conditioned Fear on Sleep.

    Science.gov (United States)

    Wellman, Laurie L; Fitzpatrick, Mairen E; Hallum, Olga Y; Sutton, Amy M; Williams, Brook L; Sanford, Larry D

    2016-06-01

    To examine the REM sleep response to stress and fearful memories as a potential marker of stress resilience and vulnerability and to assess the role of the basolateral amygdala (BLA) in mediating the effects of fear memory on sleep. Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and with bilateral guide cannulae directed at the BLA. Data loggers were placed intraperitoneally to record core body temperature. After recovery from surgery, the rats received shock training (ST: 20 footshocks, 0.8 mA, 0.5-s duration, 60-s interstimulus interval) and afterwards received microinjections of the GABAA agonist muscimol (MUS; 1.0 μM) to inactivate BLA or microinjections of vehicle (VEH) alone. Subsequently, the rats were separated into 4 groups (VEH-vulnerable (VEH-Vul; n = 14), VEH-resilient (VEH-Res; n = 13), MUS-vulnerable (MUS-Vul; n = 8), and MUS-resilient (MUS-Res; n = 11) based on whether or not REM was decreased, compared to baseline, during the first 4 h following ST. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of ST and fearful context re-exposure alone (CTX). REM was significantly reduced on the ST day in both VEH-Vul and MUS-Vul rats; however, post-ST MUS blocked the reduction in REM on the CTX day in the MUS-Vul group. The VEH-Res and MUS-Res rats showed similar levels of REM on both ST and CTX days. The effects of post-ST inactivation of BLA on freezing and SIH were minimal. Outbred Wistar rats can show significant individual differences in the effects of stress on REM that are mediated by BLA. These differences in REM can be independent of behavioral fear and the peripheral stress response, and may be an important biomarker of stress resilience and vulnerability. © 2016 Associated Professional Sleep Societies, LLC.

  19. Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Luciane B. Ceretta

    2012-01-01

    Full Text Available Diabetes Mellitus (DM is associated with pathological changes in the central nervous system (SNC as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg, and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD, and catalase (CAT were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals’ recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.

  20. Coping with stress in rats and mice : Differential peptidergic modulation of the amygdala-lateral septum complex

    NARCIS (Netherlands)

    Koolhaas, J.M.; Everts, H.G J; de Ruiter, A.J.H.; de Boer, S.F.; Bohus, B.G J

    1998-01-01

    This chapter focuses on the parvicellular vasopressin (VP) system originating from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number of limbic brain areas including the septum-hippocampal complex.

  1. Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala

    Directory of Open Access Journals (Sweden)

    Brent Myers

    2009-06-01

    Full Text Available A common characteristic of irritable bowel syndrome (IBS is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala (CeA facilitating the activation of the hypothalamic-pituitary-adrenal (HPA axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone (CORT or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor (MR and glucocorticoid receptor (GR-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS.

  2. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

  3. The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex

    OpenAIRE

    Chavez, Candice M.; McGaugh, James L.; Weinberger, Norman M.

    2008-01-01

    Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cor...

  4. Growth hormone biases amygdala network activation after fear learning

    OpenAIRE

    Gisabella, Barbara; Farah, Shadia; Peng, Xiaoyu; Burgos-Robles, Anthony Noel; Lim, Seh Hong; Goosens, Ki Ann

    2016-01-01

    Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the ?over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the proce...

  5. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

    NARCIS (Netherlands)

    Crunelle, C.L.; Kaag, A.M.; van den Munkhof, H.E.; Reneman, L.; Homberg, J.R.; Sabbe, B.; van den Brink, W.; van Wingen, G.

    2015-01-01

    OBJECTIVES: Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the

  6. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

    NARCIS (Netherlands)

    Crunelle, Cleo L.; Kaag, Anne Marije; van den Munkhof, Hanna E.; Reneman, Liesbeth; Homberg, Judith R.; Sabbe, Bernard; van den Brink, Wim; van Wingen, Guido

    2015-01-01

    Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal

  7. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval.

    Science.gov (United States)

    Vanelzakker, Michael B; Zoladz, Phillip R; Thompson, Vanessa M; Park, Collin R; Halonen, Joshua D; Spencer, Robert L; Diamond, David M

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

  8. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala and Striatum Following Long-Term Spatial Memory Retrieval

    Directory of Open Access Journals (Sweden)

    Michael B VanElzakker

    2011-06-01

    Full Text Available We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 hr later. Rat brains were extracted 30 min after the 24 hr memory test trial for analysis of c-fos mRNA. Four groups were tested: 1 Rats given standard training (Standard; 2 Rats given cat exposure (Predator Stress 30 min prior to training (Pre-Training Stress; 3 Rats given water exposure only (Water Yoked; and 4 Rats given no water exposure (Home Cage. The Standard trained group exhibited excellent 24 hr memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA. The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

  9. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

    Science.gov (United States)

    VanElzakker, Michael B.; Zoladz, Phillip R.; Thompson, Vanessa M.; Park, Collin R.; Halonen, Joshua D.; Spencer, Robert L.; Diamond, David M.

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval. PMID:21738501

  10. Cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala prevent the stress-induced enhancement of a negative learning experience.

    Science.gov (United States)

    Ramot, Assaf; Akirav, Irit

    2012-05-01

    The enhancement of emotional memory is clearly important as emotional stimuli are generally more significant than neutral stimuli for surviving and reproduction purposes. Yet, the enhancement of a negative emotional memory following exposure to stress may result in dysfunctional or intrusive memory that underlies several psychiatric disorders. Here we examined the effects of stress exposure on a negative emotional learning experience as measured by a decrease in the magnitude of the expected quantity of reinforcements in an alley maze. In contrast to other fear-related negative experiences, reward reduction is more associated with frustration and is assessed by measuring the latency to run the length of the alley to consume the reduced quantity of reward. We also examined whether the cannabinoid receptors agonist WIN55,212-2 (5 μg/side) and the glucocorticoid receptors (GRs) antagonist RU-486 (10 ng/side) administered into the rat basolateral amygdala (BLA) could prevent the stress-induced enhancement. We found that intra-BLA RU-486 or WIN55,212 before stress exposure prevented the stress-induced enhancement of memory consolidation for reduction in reward magnitude. These findings suggest that cannabinoid receptors and GRs in the BLA are important modulators of stress-induced enhancement of emotional memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Modeling a Negative Response Bias in the Human Amygdala by Noradrenergic-Glucocorticoid Interactions

    NARCIS (Netherlands)

    Kukolja, Juraj; Schlaepfer, Thomas E.; Keysers, Christian; Klingmueller, Dietrich; Maier, Wolfgang; Fink, Gereon R.; Hurlemann, Rene

    2008-01-01

    An emerging theme in the neuroscience of emotion is the question of how acute stress shapes, and distorts, social-emotional behavior. The prevailing neurocircuitry models of social-emotional behavior emphasize the central role of the amygdala. Acute stress leads to increased central levels of

  12. Academic stress and personality interact to increase the neural response to high-calorie food cues.

    Science.gov (United States)

    Neseliler, Selin; Tannenbaum, Beth; Zacchia, Maria; Larcher, Kevin; Coulter, Kirsty; Lamarche, Marie; Marliss, Errol B; Pruessner, Jens; Dagher, Alain

    2017-09-01

    Psychosocial stress is associated with an increased intake of palatable foods and weight gain in stress-reactive individuals. Personality traits have been shown to predict stress-reactivity. However, it is not known if personality traits influence brain activity in regions implicated in appetite control during psychosocial stress. The current study assessed whether Gray's Behavioural Inhibition System (BIS) scale, a measure of stress-reactivity, was related to the activity of brain regions implicated in appetite control during a stressful period. Twenty-two undergraduate students participated in a functional magnetic resonance imaging (fMRI) experiment once during a non-exam period and once during final exams in a counter-balanced order. In the scanner, they viewed food and scenery pictures. In the exam compared with the non-exam condition, BIS scores related to increased perceived stress and correlated with increased blood-oxygen-level dependent (BOLD) response to high-calorie food images in regions implicated in food reward and subjective value, such as the ventromedial prefrontal cortex, (vmPFC) and the amygdala. BIS scores negatively related to the functional connectivity between the vmPFC and the dorsolateral prefrontal cortex. The results demonstrate that the BIS trait influences stress reactivity. This is observed both as an increased activity in brain regions implicated in computing the value of food cues and decreased connectivity of these regions to prefrontal regions implicated in self-control. This suggests that the effects of real life stress on appetitive brain function and self-control is modulated by a personality trait. This may help to explain why stressful periods can lead to overeating in vulnerable individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Stress Sensitive Healthy Females Show Less Left Amygdala Activation in Response to Withdrawal-Related Visual Stimuli under Passive Viewing Conditions

    Science.gov (United States)

    Baeken, Chris; Van Schuerbeek, Peter; De Raedt, Rudi; Vanderhasselt, Marie-Anne; De Mey, Johan; Bossuyt, Axel; Luypaert, Robert

    2012-01-01

    The amygdalae are key players in the processing of a variety of emotional stimuli. Especially aversive visual stimuli have been reported to attract attention and activate the amygdalae. However, as it has been argued that passively viewing withdrawal-related images could attenuate instead of activate amygdalae neuronal responses, its role under…

  14. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

    Directory of Open Access Journals (Sweden)

    Carmela Giordano

    Full Text Available Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

  15. Emotional Memory Formation Under Lower Versus Higher Stress Conditions

    OpenAIRE

    Kogan, Inna; Richter-Levin, Gal

    2010-01-01

    An exposure to stress can enhance memory for emotionally arousing experiences. The phenomenon is suggested to be amygdala-dependent and in accordance with that view the amygdala was found to modulate mnemonic processes in other brain regions. Previously, we illustrated increased amygdala activation and reduced activation of CA1 following spatial learning under higher versus lower stress conditions. When spatial learning was followed by reversal training interference, impaired retention was de...

  16. Time-dependent effects of corticosteroids on human amygdala processing

    NARCIS (Netherlands)

    Henckens, M.J.A.G.; van Wingen, G.A.; Joëls, M.; Fernández, G.

    2010-01-01

    Acute stress is associated with a sensitized amygdala. Corticosteroids, released in response to stress, are suggested to restore homeostasis by normalizing/desensitizing brain processing in the aftermath of stress. Here, we investigated the effects of corticosteroids on amygdala processing using

  17. Regulation of the fear network by mediators of stress: Norepinephrine alters the balance between Cortical and Subcortical afferent excitation of the Lateral Amygdala

    Directory of Open Access Journals (Sweden)

    Luke R Johnson

    2011-05-01

    Full Text Available Pavlovian auditory fear conditioning crucially involves the integration of information about and acoustic conditioned stimulus (CS and an aversive unconditioned stimulus (US in the lateral nucleus of the amygdala (LA. The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE, regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased towards the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance towards the faster but more primitive subcortical input.

  18. Women with multiple chemical sensitivity have increased harm avoidance and reduced 5-HT(1A receptor binding potential in the anterior cingulate and amygdala.

    Directory of Open Access Journals (Sweden)

    Lena Hillert

    Full Text Available Multiple chemical sensitivity (MCS is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22-44, all working or studying females, were included in a PET study where 5-HT(1A receptor binding potential (BP was assessed after bolus injection of [(11C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT(1A receptor BP in amygdala (p = 0.029, ACC (p = 0.005 (planned comparisons, significance level 0.05, and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction, and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison. No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT(1A receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances.

  19. 5-HT1A receptor blockade targeting the basolateral amygdala improved stress-induced impairment of memory consolidation and retrieval in rats.

    Science.gov (United States)

    Sardari, M; Rezayof, A; Zarrindast, M-R

    2015-08-06

    The aim of the present study was to investigate the possible role of basolateral amygdala (BLA) 5-HT1A receptors in memory formation under stress. We also examined whether the blockade of these receptors is involved in stress-induced state-dependent memory. Adult male Wistar rats received cannula implants that bilaterally targeted the BLA. Long-term memory was examined using the step-through type of passive avoidance task. Behavioral stress was evoked by exposure to an elevated platform (EP) for 10, 20 and 30min. Post-training exposure to acute stress (30min) impaired the memory consolidation. In addition, pre-test exposure to acute stress-(20 and 30min) induced the impairment of memory retrieval. Interestingly, the memory impairment induced by post-training exposure to stress was restored in the animals that received 20- or 30-min pre-test stress exposure, suggesting stress-induced state-dependent memory retrieval. Post-training BLA-targeted injection of a selective 5-HT1A receptor antagonist, (S)-WAY-100135 (2μg/rat), prevented the impairing effect of stress on memory consolidation. Pre-test injection of the same doses of (S)-WAY-100135 that was targeted to the BLA also reversed stress-induced memory retrieval impairment. It should be considered that post-training or pre-test BLA-targeted injection of (S)-WAY-100135 (0.5-2μg/rat) by itself had no effect on the memory formation. Moreover, pre-test injection of (S)-WAY-100135 (2μg/rat) that targeted the BLA inhibited the stress-induced state-dependent memory retrieval. Taken together, our findings suggest that post-training or pre-test exposure to acute stress induced the impairment of memory consolidation, retrieval and state-dependent learning. The BLA 5-HT1A receptors have a critical role in learning and memory under stress. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Extending the amygdala in theories of threat processing

    Science.gov (United States)

    Fox, Andrew S.; Oler, Jonathan A.; Tromp, Do P.M.; Fudge, Julie L.; Kalin, Ned H.

    2015-01-01

    The central extended amygdala is an evolutionarily conserved set of interconnected brain regions that play an important role in threat processing to promote survival. Two core components of the central extended amygdala, the central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria terminalis (BST) are highly similar regions that serve complimentary roles by integrating fear- and anxiety-relevant information. Survival depends on the central extended amygdala's ability to rapidly integrate and respond to threats that vary in their immediacy, proximity, and characteristics. Future studies will benefit from understanding alterations in central extended amygdala function in relation to stress-related psychopathology. PMID:25851307

  1. Pre-cold stress increases acid stress resistance and induces amino ...

    African Journals Online (AJOL)

    Pre-cold stress increases acid stress resistance and induces amino acid homeostasis in Lactococcus lactis NZ9000. ... Purpose: To investigate the effects of pre-cold stress treatments on subsequent acid stress resistance ... from 32 Countries:.

  2. Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD.

    Science.gov (United States)

    Tsoory, M M; Vouimba, R M; Akirav, I; Kavushansky, A; Avital, A; Richter-Levin, G

    2008-01-01

    A key assumption in the study of stress-induced cognitive and neurobiological modifications is that alterations in hippocampal functioning after stress are due to an excessive activity exerted by the amygdala on the hippocampus. Research so far focused on stress-induced impairment of hippocampal plasticity and memory but an exposure to stress may simultaneously also result in strong emotional memories. In fact, under normal conditions emotionally charged events are better remembered compared with neutral ones. Results indicate that under these conditions there is an increase in activity within the amygdala that may lead to memory of a different quality. Studying the way emotionality activates the amygdala and the functional impact of this activation we found that the amygdala modulates memory-related processes in other brain areas, such as the hippocampus. However, this modulation is complex, involving both enhancing and suppressing effects, depending on the way the amygdala is activated and the hippocampal subregion examined. The current review summarizes our findings and attempts to put them in context with the impact of an exposure to a traumatic experience, in which there is a mixture of a strong memory of some aspects of the experience but impaired memory of other aspects of that experience. Toward that end, we have recently developed an animal model for the induction of predisposition to stress-related disorders, focusing on the consequences of exposure to stressors during juvenility on the ability to cope with stress in adulthood. Exposing juvenile-stressed rats to an additional stressful challenge in adulthood revealed their impairment to cope with stress and resulted in significant elevation of the amygdala. Interestingly, and similar to our electrophysiological findings, differential effects were observed between the impact of the emotional challenge on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the results indicate that long

  3. Juvenile obesity enhances emotional memory and amygdala plasticity through glucocorticoids.

    Science.gov (United States)

    Boitard, Chloé; Maroun, Mouna; Tantot, Frédéric; Cavaroc, Amandine; Sauvant, Julie; Marchand, Alain; Layé, Sophie; Capuron, Lucile; Darnaudery, Muriel; Castanon, Nathalie; Coutureau, Etienne; Vouimba, Rose-Marie; Ferreira, Guillaume

    2015-03-04

    In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence during adolescence is particularly alarming since recent evidence indicates that obesity can affect hippocampal function during this developmental period. Adolescence is a decisive period for maturation of the amygdala and the hypothalamic-pituitary-adrenal (HPA) stress axis, both required for lifelong cognitive and emotional processing. However, little data are available on the impact of obesity during adolescence on amygdala function. Herein, we therefore evaluate in rats whether juvenile high-fat diet (HFD)-induced obesity alters amygdala-dependent emotional memory and whether it depends on HPA axis deregulation. Exposure to HFD from weaning to adulthood, i.e., covering adolescence, enhances long-term emotional memories as assessed by odor-malaise and tone-shock associations. Juvenile HFD also enhances emotion-induced neuronal activation of the basolateral complex of the amygdala (BLA), which correlates with protracted plasma corticosterone release. HFD exposure restricted to adulthood does not modify all these parameters, indicating adolescence is a vulnerable period to the effects of HFD-induced obesity. Finally, exaggerated emotional memory and BLA synaptic plasticity after juvenile HFD are alleviated by a glucocorticoid receptor antagonist. Altogether, our results demonstrate that juvenile HFD alters HPA axis reactivity leading to an enhancement of amygdala-dependent synaptic and memory processes. Adolescence represents a period of increased susceptibility to the effects of diet-induced obesity on amygdala function. Copyright © 2015 the authors 0270-6474/15/354092-12$15.00/0.

  4. Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex.

    Science.gov (United States)

    Feng, Pan; Becker, Benjamin; Zheng, Yong; Feng, Tingyong

    2018-02-01

    Sleep plays an important role for successful fear memory consolidation. Growing evidence suggests that sleep disturbances might contribute to the development and the maintenance of posttraumatic stress disorder (PTSD), a disorders characterized by dysregulations in fear learning mechanisms, as well as exaggerated arousal and salience processing. Against this background, the present study examined the effects of sleep deprivation (SD) on the acquisition of fear and the subsequent neural consolidation. To this end, the present study assessed fear acquisition and associated changes in fMRI-based amygdala-functional connectivity following 24 h of SD. Relative to non-sleep deprived controls, SD subjects demonstrated increased fear ratings and skin conductance responses (SCR) during fear acquisition. During fear consolidation SD inhibited increased amygdala-ventromendial prefrontal cortex (vmPFC) connectivity and concomitantly increased changes in amygdala-insula connectivity. Importantly, whereas in controls fear indices during acquisition were negatively associated with amygdala-vmPFC connectivity during consolidation, fear indices were positively associated with amygdala-insula coupling following SD. Together the findings suggest that SD may interfere with vmPFC control of the amygdala and increase bottom-up arousal signaling in the amygdala-insula pathway during fear consolidation, which might mediate the negative impact of sleep disturbances on PSTD symptomatology.

  5. Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior. Study 1--Role of NMDA receptors in efferent transmission from the cat amygdala.

    Science.gov (United States)

    Adamec, R E

    1998-01-01

    The anxiogenic beta-carboline, FG-7142, produces intense anxiety in humans and anxiety-like behavior in animals. FG-7142 also mimics the effects of exogenous stressors. In cats, FG-7142 lastingly changes defensive and aggressive behavior. Long-term potentiation (LTP) of neural transmission between limbic structures known to modulate feline defensive response to threat accompany behavioral changes. A series of three reports describes experiments designed to test the hypothesis that behavioral changes depend upon an N-methyl-D-aspartate (NMDA) receptor-based LTP of efferent transmission from the amygdala. This first study characterizes the dose and time effects of injection of the NMDA receptor blocker 7-amino-phosphono-heptanoic acid (AP7) on efferent transmission from the cat amygdala to the ventromedial hypothalamus (VMH). Effects of doses of 0.5-10mg/kg (i.v.) of AP7 on potentials evoked in the VMH by single pulse stimulation of the basal amygdala were examined. In order to localize the action of the drug, concurrent measurements were taken of potentials evoked in the VMH by stimulation of the efferent fibers from the amygdala to the VMH (ventral amygdalofugal pathway, VAF). There was a dose-dependent reduction in the amygdalo-VMH evoked potential. The greatest reduction occurred at 5 mg/kg. Effects peaked at 10 min, and persisted for at least 1 h after injection. In contrast, AP7 increased the VAF-VMH-evoked potential at 10 min after injection, with a maximal increase at 5mg/kg. The data suggest that NMDA receptors intrinsic to the amygdala modulate excitatory efferent transmission from amygdala to VMH in the cat. It is speculated that a glutamatergic projection to gamma-aminobutyric acid tonic inhibitory systems in the VMH accounts for the VAF-VMH results.

  6. Divergent responses of the amygdala and ventral striatum predict stress-related problem drinking in young adults: possible differential markers of affective and impulsive pathways of risk for alcohol use disorder.

    Science.gov (United States)

    Nikolova, Y S; Knodt, A R; Radtke, S R; Hariri, A R

    2016-03-01

    Prior work suggests that there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and another associated with negative emotion relief and coping. We sought to map these two pathways onto individual differences in neural reward and threat processing assessed using blood-oxygen-level-dependent functional magnetic resonance imaging in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24 years) participating in the Duke Neurogenetics Study. We demonstrate that problem drinking is highest in the context of stress and in those with one of two distinct neural phenotypes: (1) a combination of relatively low reward-related activity of the ventral striatum (VS) and high threat-related reactivity of the amygdala; or (2) a combination of relatively high VS activity and low amygdala reactivity. In addition, we demonstrate that the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in monetary delay discounting rates, for those with high VS-low amygdala reactivity, and by anxious/depressive symptomatology for those with the opposite neural risk phenotype. Across both neural phenotypes, we found that greater divergence between VS and amygdala reactivity predicted greater risk for problem drinking. Finally, for those individuals with the low VS-high amygdala risk phenotype we found that stress not only predicted the presence of AUD diagnosis at the time of neuroimaging but also subsequent problem drinking reported 3 months following study completion. These results offer new insight into the neural basis of AUD risk and suggest novel biological targets for early individualized treatment or prevention.

  7. Divergent responses of the amygdala and ventral striatum predict stress-related problem drinking in young adults: Possible differential markers of affective and impulsive pathways of risk for alcohol use disorder

    Science.gov (United States)

    Nikolova, Yuliya S.; Knodt, Annchen R.; Radtke, Spenser R.; Hariri, Ahmad R.

    2015-01-01

    Prior work suggests there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and one associated with negative emotion relief and coping. We sought to map these two pathways onto individual differences in neural reward and threat processing assessed using BOLD fMRI in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24) participating in the Duke Neurogenetics Study. We demonstrate that problem drinking is highest in the context of stress and in those with one of two distinct neural phenotypes: 1) a combination of relatively low reward-related activity of the ventral striatum (VS) and high threat-related reactivity of the amygdala; or 2) a combination of relatively high VS activity and low amygdala reactivity. In addition, we demonstrate that the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in monetary delay discounting rates, for those with high VS-low amygdala reactivity, and by anxious/depressive symptomatology for those with the opposite neural risk phenotype. Across both neural phenotypes, we found that greater divergence between VS and amygdala reactivity predicted greater risk for problem drinking. Finally, for those individuals with the low VS-high amygdala risk phenotype we found that stress not only predicted the presence of a DSM-IV diagnosed AUD at the time of neuroimaging, but also subsequent problem drinking reported three months following study completion. These results offer new insight into the neural basis of AUD risk and suggest novel biological targets for early individualized treatment or prevention. PMID:26122584

  8. 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...

  9. Aberrant Functional Connectivity of the Amygdala Complexes in PTSD during Conscious and Subconscious Processing of Trauma-Related Stimuli.

    Directory of Open Access Journals (Sweden)

    Daniela Rabellino

    Full Text Available Post-traumatic stress disorder (PTSD is characterized by altered functional connectivity of the amygdala complexes at rest. However, amygdala complex connectivity during conscious and subconscious threat processing remains to be elucidated. Here, we investigate specific connectivity of the centromedial amygdala (CMA and basolateral amygdala (BLA during conscious and subconscious processing of trauma-related words among individuals with PTSD (n = 26 as compared to non-trauma-exposed controls (n = 20. Psycho-physiological interaction analyses were performed using the right and left amygdala complexes as regions of interest during conscious and subconscious trauma word processing. These analyses revealed a differential, context-dependent responses by each amygdala seed during trauma processing in PTSD. Specifically, relative to controls, during subconscious processing, individuals with PTSD demonstrated increased connectivity of the CMA with the superior frontal gyrus, accompanied by a pattern of decreased connectivity between the BLA and the superior colliculus. During conscious processing, relative to controls, individuals with PTSD showed increased connectivity between the CMA and the pulvinar. These findings demonstrate alterations in amygdala subregion functional connectivity in PTSD and highlight the disruption of the innate alarm network during both conscious and subconscious trauma processing in this disorder.

  10. How acute stress may enhance subsequent memory for threat stimuli outside the focus of attention: DLPFC-amygdala decoupling

    NARCIS (Netherlands)

    Luo, Y.; Fernandez, G.S.E.; Hermans, E.; Vogel, S.; Zhang, Y.; Li, H.; Klumpers, F.

    2018-01-01

    Stress-related disorders, e.g., anxiety and depression, are characterized by decreased top-down control for distracting information, as well as a memory bias for threatening information. However, it is unclear how acute stress biases mnemonic encoding and leads to prioritized storage of

  11. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

    Directory of Open Access Journals (Sweden)

    Neugebauer Volker

    2010-12-01

    Full Text Available Abstract Neuroplasticity in the central nucleus of the amygdala (CeA, particularly its latero-capsular division (CeLC, is an important contributor to the emotional-affective aspects of pain. Previous studies showed synaptic plasticity of excitatory transmission to the CeLC in different pain models, but pain-related changes of inhibitory transmission remain to be determined. The CeLC receives convergent excitatory inputs from the parabrachial nucleus in the brainstem and from the basolateral amygdala (BLA. In addition, feedforward inhibition of CeA neurons is driven by glutamatergic projections from the BLA area to a cluster of GABAergic neurons in the intercalated cell masses (ITC. Using patch-clamp in rat brain slices we measured monosynaptic excitatory postsynaptic currents (EPSCs and polysynaptic inhibitory currents (IPSCs that were evoked by electrical stimulation in the BLA. In brain slices from arthritic rats, input-output functions of excitatory synaptic transmission were enhanced whereas inhibitory synaptic transmission was decreased compared to control slices from normal untreated rats. A non-NMDA receptor antagonist (NBQX blocked the EPSCs and reduced the IPSCs, suggesting that non-NMDA receptors mediate excitatory transmission and also contribute to glutamate-driven feed-forward inhibition of CeLC neurons. IPSCs were blocked by a GABAA receptor antagonist (bicuculline. Bicuculline increased EPSCs under normal conditions but not in slices from arthritic rats, which indicates a loss of GABAergic control of excitatory transmission. A metabotropic glutamate receptor subtype 1 (mGluR1 antagonist (LY367385 reversed both the increase of excitatory transmission and the decrease of inhibitory transmission in the arthritis pain model but had no effect on basal synaptic transmission in control slices from normal rats. The inhibitory effect of LY367385 on excitatory transmission was blocked by bicuculline suggesting the involvement of a GABAergic

  12. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

    Takaaki Tomofuji; Koichiro Irie; Toshihiro Sanbe; Tetsuji Azuma; Daisuke Ekuni; Naofumi Tamaki; Tatsuo Yamamoto; Manabu Morita

    2009-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress). Such oxidation may be detrimental to systemic health. Fo...

  13. Noradrenergic enhancement of amygdala responses to fear

    NARCIS (Netherlands)

    Onur, Oezguer A; Walter, Henrik; Schlaepfer, Thomas E; Rehme, Anne K; Schmidt, Christoph; Keysers, Christian; Maier, Wolfgang; Hurlemann, René

    Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no

  14. Amygdala Functional Connectivity is Reduced After the Cold Pressor Task

    Science.gov (United States)

    Clewett, David; Schoeke, Andrej; Mather, Mara

    2013-01-01

    The amygdala forms a crucial link between central pain and stress systems. There is much evidence that psychological stress affects amygdala activity, but it is less clear how painful stressors influence subsequent amygdala functional connectivity. In the present study, we used pulsed arterial spin labeling (PASL) to investigate differences in healthy male adults’ resting-state amygdala functional connectivity following a cold pressor versus control task, with the stressor and control conditions conducted on different days. During the period of peak cortisol response to acute stress (approximately fifteen to thirty minutes after stressor onset), participants were asked to rest for six minutes with their eyes closed during a PASL scanning sequence. The cold pressor task led to reduced resting-state functional connectivity between the amygdalae and orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC), which occurred irrespective of cortisol release. The stressor also induced greater inverse connectivity between the left amygdala and dorsal anterior cingulate cortex (dACC), a brain region implicated in the down-regulation of amygdala responsivity. Furthermore, the degree of post-stressor left amygdala decoupling with the lateral OFC varied according to self-reported pain intensity during the cold pressor task. These findings indicate that the cold pressor task alters amygdala interactions with prefrontal and ACC regions 15–30 minutes after the stressor, and that these altered functional connectivity patterns are related to pain perception rather than cortisol feedback. PMID:23645370

  15. Fluoxetine pretreatment promotes neuronal survival and maturation after auditory fear conditioning in the rat amygdala.

    Directory of Open Access Journals (Sweden)

    Lizhu Jiang

    Full Text Available The amygdala is a critical brain region for auditory fear conditioning, which is a stressful condition for experimental rats. Adult neurogenesis in the dentate gyrus (DG of the hippocampus, known to be sensitive to behavioral stress and treatment of the antidepressant fluoxetine (FLX, is involved in the formation of hippocampus-dependent memories. Here, we investigated whether neurogenesis also occurs in the amygdala and contributes to auditory fear memory. In rats showing persistent auditory fear memory following fear conditioning, we found that the survival of new-born cells and the number of new-born cells that differentiated into mature neurons labeled by BrdU and NeuN decreased in the amygdala, but the number of cells that developed into astrocytes labeled by BrdU and GFAP increased. Chronic pretreatment with FLX partially rescued the reduction in neurogenesis in the amygdala and slightly suppressed the maintenance of the long-lasting auditory fear memory 30 days after the fear conditioning. The present results suggest that adult neurogenesis in the amygdala is sensitive to antidepressant treatment and may weaken long-lasting auditory fear memory.

  16. The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response.

    Science.gov (United States)

    Wellman, Laurie L; Fitzpatrick, Mairen E; Hallum, Olga Y; Sutton, Amy M; Williams, Brook L; Sanford, Larry D

    2017-01-01

    Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABA A agonist, muscimol (Mus), to inactivate BLA prior to CR and examined the effects on sleep, freezing and stress-induced hyperthermia (SIH). Wistar rats (n=28) were implanted with electrodes for recording sleep, data loggers for recording core body temperature, and with cannulae aimed bilaterally into BLA. After recovery, the animals were habituated to the injection procedure and baseline sleep was recorded. On experimental day 1, rats received ST (20 footshocks, 0.8mA, 0.5s duration, 60s interstimulus interval). On experimental day 7, the rats received microinjections (0.5μl) into BLA of either Mus (1.0μM; n=13) or vehicle (Veh; n=15) prior to CR (CR1). On experimental day 21, the animals experienced a second CR (CR2) without Mus. For analysis, the rats were separated into 4 groups: (Veh-vulnerable (Veh-Vul; n=8), Veh-resilient (Veh-Res; n=7), Mus-vulnerable (Mus-Vul; n=7), and Mus-resilient (Mus-Res; n=6)) based on whether or not REM was decreased, compared to baseline, during the first 4h following ST. Pre-CR1 inactivation of BLA did not alter freezing or SIH, but did block the reduction in REM in the Mus-Vul group compared to the Veh-Vul group. These data indicate that BLA is an important region for mediating the effects of fearful memories on sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Prenatal stress may increase vulnerability to life events

    DEFF Research Database (Denmark)

    Hougaard, Karin S; Andersen, Maibritt B; Kjaer, Sanna L

    2005-01-01

    Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...

  18. Testosterone reduces amygdala-orbitofrontal cortex coupling

    NARCIS (Netherlands)

    van Wingen, Guido; Mattern, Claudia; Verkes, Robbert Jan; Buitelaar, Jan; Fernández, Guillén

    2010-01-01

    Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered

  19. Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Kymberly D. Young

    2018-01-01

    Conclusions: Neurofeedback training to increase amygdala hemodynamic activity during positive AM recall increased amygdala connectivity with regions involved in self-referential, salience, and reward processing. Results suggest future targets for neurofeedback interventions, particularly interventions involving the precuneus.

  20. Pad stress tests with increasing load for the diagnosis of stress urinary incontinence.

    Science.gov (United States)

    Rimstad, Liv; Larsen, Elsa Skjønhaug; Schiøtz, Hjalmar A; Kulseng-Hanssen, Sigurd

    2014-09-01

    The aim of the study was to test the ability of pad stress tests with increasing load (supine, jumping on the floor, and jumping on a trampoline) to document stress incontinence in subjectively stress incontinent women. In this prospective study 147 subjectively stress and mixed incontinent women performed consecutively the three pad stress tests with a bladder volume of 300 ml. Nineteen women performed a second trampoline pad stress test to test repeatability of the test. Nine continent women performed a trampoline pad stress test in order to determine if subjectively continent women would leak during the test. Seventy-two women (49%) leaked during the supine, 136 (93%) leaked during the jumping, and 146 (99%) leaked during the trampoline pad stress test. The differences between pad stress tests were significant with P trampoline pad stress tests was high at 0.8. None of the nine continent women leaked during the trampoline pad stress test. The supine pad stress test has low sensitivity and is therefore often falsely negative. The jumping pad stress test is a simple test to perform and is satisfactory for everyday use. Subjectively stress incontinent women who do not leak during the jumping pad stress test may perform a trampoline pad stress test to document stress incontinence. The trampoline pad stress test is also simple to perform and detected leakage in 91% of the women who did not leak during the jumping pad stress test. © 2013 Wiley Periodicals, Inc.

  1. Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation.

    Science.gov (United States)

    Koek, Ralph J; Langevin, Jean-Philippe; Krahl, Scott E; Kosoyan, Hovsep J; Schwartz, Holly N; Chen, James W Y; Melrose, Rebecca; Mandelkern, Mark J; Sultzer, David

    2014-09-10

    Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS. We describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked 18FDG PET metabolic changes in limbic circuitry will also be evaluated. While the rationale for studying DBS

  2. Increased neural responses to empathy for pain might explain how acute stress increases prosociality

    OpenAIRE

    Tomova, L.; Majdand?i?, J.; Hummer, A.; Windischberger, C.; Heinrichs, M.; Lamm, C.

    2016-01-01

    Abstract Recent behavioral investigations suggest that acute stress can increase prosocial behavior. Here, we investigated whether increased empathy represents a potential mechanism for this finding. Using functional magnetic resonance imaging, we assessed the effects of acute stress on neural responses related to automatic and regulatory components of empathy for pain as well as subsequent prosocial behavior. Stress increased activation in brain areas associated with the automatic sharing of...

  3. 15. Amygdala pain mechanisms

    Science.gov (United States)

    Neugebauer, Volker

    2015-01-01

    A limbic brain area the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety and depression. The amygdala has also emerged as an important brain center for the emotional-affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the “nociceptive amygdala”) accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms. PMID:25846623

  4. Impact of family history and depression on amygdala volume.

    LENUS (Irish Health Repository)

    Saleh, Karim

    2012-07-30

    Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study\\'s purpose was to investigate family history\\'s effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18-65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala without a family history of MDD. These effects had larger right amygdala than healthy controls without MDD family history. These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants, providing a rationale for the inconsistent results in MDD amygdala studies. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.

  5. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    Background: Chronic hyperglycaemia in diabetes mellitus leads to increased lipid peroxidation in the body, followed by the development of chronic complications due to oxidative stress. Objective: The aim of this study was to compare total antioxidant (TAO) levels and oxidative stress in type 2 diabetes mellitus (T2DM) ...

  6. Isothermal martensitic transformation as an internal-stress-increasing process

    International Nuclear Information System (INIS)

    Liu, Y.; Xie, Z.L.; Haenninen, H.; Humbeeck, J. van; Pietikaeinen, J.

    1995-01-01

    Based on the results that the magnitude of the stabilization of retained austenite increases with increasing the amount of martensite transformed, it has been assumed that the martensitic transformation is accompanied with an increase in internal resisting stress which subsequently results in the stabilization of retained austenite. By simplifying this internal resisting stress to be a type of hydrostatic compressive stress acting on retained austenite due to surrounding martensite plates, a thermodynamical analysis for an isothermal martensitic transformation under applied hydrostatic pressure has been performed. The calculated results, to some extent, show a good agreement with the experimental data. (orig.)

  7. Structural Connectivity of the Developing Human Amygdala

    Science.gov (United States)

    Saygin, Zeynep M.; Osher, David E.; Koldewyn, Kami; Martin, Rebecca E.; Finn, Amy; Saxe, Rebecca; Gabrieli, John D.E.; Sheridan, Margaret

    2015-01-01

    A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age. PMID:25875758

  8. Memory-enhancing intra-basolateral amygdala infusions of clenbuterol increase Arc and CaMKII-alpha protein expression in the rostral anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Crystal M Holloway-Erickson

    2012-04-01

    Full Text Available Activation of β-adrenoceptors in the basolateral complex of the amygdala (BLA modulates memory through interactions with multiple memory systems. The cellular mechanisms for this interaction remain unresolved. Memory-modulating BLA manipulations influence expression of the protein product of the immediate early gene activity-regulated cytoskeletal-associated protein (Arc in the dorsal hippocampus, and hippocampal expression of Arc protein is critically involved in memory consolidation and long-term potentiation. The present studies examined whether this influence of the BLA is specific to the hippocampus and to Arc protein. Like the hippocampus, the rostral portion of the anterior cingulate cortex (rACC is involved in the consolidation of inhibitory avoidance (IA memory, and IA training increases Arc protein in the rACC. Because the BLA interacts with the rACC in the consolidation of IA memory, the rACC is a potential candidate for further studies of BLA modulation of synaptic plasticity. The alpha isoform of the Calcium/Calmodulin-dependent protein kinase II (CaMKIIα and the immediate early gene c-Fos are involved in long-term potentiation and memory. Both Arc and CaMKIIα proteins can be translated in isolated synapses, where the mRNA is localized, but c-Fos protein remains in the soma. To examine the influence of memory-modulating manipulations of the BLA on expression of these memory and plasticity-associated proteins in the rACC, male Sprague-Dawley rats were trained on an IA task and given intra-BLA infusions of either clenbuterol or lidocaine immediately after training. Findings suggest that noradrenergic stimulation of the BLA may modulate memory consolidation through effects on both synaptic proteins Arc and CaMKIIα, but not the somatic protein c-Fos. Furthermore, protein changes observed in the rACC following BLA manipulations suggest that the influence of the BLA on synaptic proteins is not limited to those in the dorsal

  9. Increased oxidative stress in patients with familial Mediterranean ...

    African Journals Online (AJOL)

    0.05) comparing to HC group. However, there were no statistically significant differences between the groups in terms of antioxidant vitamin levels. Conclusions: Our study demonstrated increased oxidative stress in patients with FMF during AP.

  10. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    21–25 ... Decreased total antioxidant levels and increased oxidative stress in South ... antioxidant-rich diet and lifestyle changes in T2DM patients would help to avert the .... glycation of proteins and the formation of advanced glycosylation.

  11. Acute stress decreases but chronic stress increases myocardial sensitivity to ischemic injury in rodents

    Directory of Open Access Journals (Sweden)

    Eric D Eisenmann

    2016-04-01

    Full Text Available Cardiovascular disease is the largest cause of mortality worldwide, and stress is a significant contributor to the development of cardiovascular disease. The relationship between acute and chronic stress and cardiovascular disease is well-evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury. Conversely, chronic stress is arrythmogenic and increases sensitivity to myocardial ischemia-reperfusion injury. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

  12. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

    Science.gov (United States)

    Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

  13. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    Science.gov (United States)

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  14. The amygdala: securing pleasure and avoiding pain

    Directory of Open Access Journals (Sweden)

    Anushka B P Fernando

    2013-12-01

    Full Text Available The amygdala has traditionally been associated with fear, mediating the impact of negative emotions on memory. However, this view does not fully encapsulate the function of the amygdala, nor the impact that processing in this structure has on the motivational limbic corticostriatal circuitry of which it is an important structure. Here we discuss the interactions between different amygdala nuclei with cortical and striatal regions involved in motivation; interconnections and parallel circuitries that have become increasingly understood in recent years. We review the evidence that the amygdala stores memories that allow initially motivationally neutral stimuli to become associated through pavlovian conditioning with motivationally relevant outcomes which, importantly, can be either appetitive (e.g. food or aversive (e.g. electric shock. We also consider how different psychological processes supported by the amygdala such as conditioned reinforcement and punishment, conditioned motivation and suppression, and conditioned approach and avoidance behavior, are not only psychologically but also neurobiologically dissociable, being mediated by distinct yet overlapping neural circuits within the limbic corticostriatal circuitry. Clearly the role of the amygdala goes beyond encoding aversive stimuli to also encode the appetitive, requiring an appreciation of the amygdala’s mediation of both appetitive and fearful behavior through diverse psychological processes.

  15. FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity.

    Science.gov (United States)

    White, M G; Bogdan, R; Fisher, P M; Muñoz, K E; Williamson, D E; Hariri, A R

    2012-10-01

    Individual variation in physiological responsiveness to stress mediates risk for mental illness and is influenced by both experiential and genetic factors. Common polymorphisms in the human gene for FK506 binding protein 5 (FKBP5), which is involved in transcriptional regulation of the hypothalamic-pituitary-adrenal (HPA) axis, have been shown to interact with childhood abuse and trauma to predict stress-related psychopathology. In the current study, we examined if such gene-environment interaction effects may be related to variability in the threat-related reactivity of the amygdala, which plays a critical role in mediating physiological and behavioral adaptations to stress including modulation of the HPA axis. To this end, 139 healthy Caucasian youth completed a blood oxygen level-dependent functional magnetic resonance imaging probe of amygdala reactivity and self-report assessments of emotional neglect (EN) and other forms of maltreatment. These individuals were genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously associated with psychopathology and/or HPA axis function. Interactions between each SNP and EN emerged such that risk alleles predicted relatively increased dorsal amygdala reactivity in the context of higher EN, even after correcting for multiple testing. Two different haplotype analyses confirmed this relationship as haplotypes with risk alleles also exhibited increased amygdala reactivity in the context of higher EN. Our results suggest that increased threat-related amygdala reactivity may represent a mechanism linking psychopathology to interactions between common genetic variants affecting HPA axis function and childhood trauma. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  16. Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

    Science.gov (United States)

    Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

    2016-12-01

    Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

  17. Amygdala Hyperactivity at Rest in Paranoid Individuals With Schizophrenia.

    Science.gov (United States)

    Pinkham, Amy E; Liu, Peiying; Lu, Hanzhang; Kriegsman, Michael; Simpson, Claire; Tamminga, Carol

    2015-08-01

    The amygdala's role in threat perception suggests that increased activation of this region may be related to paranoid ideation. However, investigations of amygdala function in paranoid individuals with schizophrenia, compared with both healthy individuals and nonparanoid individuals with schizophrenia, have consistently reported reduced task-related activation. The reliance of blood-oxygen-level-dependent functional MRI on a contrast between events and baseline, and the inability to quantitatively measure this baseline, may account for these counterintuitive findings. The present study tested for differences in baseline levels of amygdala activity in paranoid and nonparanoid individuals with schizophrenia using arterial spin labeling perfusion MRI. Resting cerebral blood flow (CBF) and task-related activation of the amygdala were measured in 25 healthy individuals, 16 individuals with schizophrenia who were actively paranoid at the time of scanning, and 16 individuals with schizophrenia who were not paranoid. Analysis of relative CBF values extracted from the amygdala bilaterally revealed significantly increased activity in the left amygdala in paranoid patient volunteers compared with healthy comparison subjects and nonparanoid patient volunteers. Increased CBF was also evident in the right amygdala but did not reach the level of statistical significance. Paranoid volunteers also showed significantly decreased task-related activation of the amygdala compared with the two other groups. These findings suggest that amygdala hyperactivation may underlie paranoia in schizophrenia. Additionally, the reported differences between paranoid and nonparanoid patient volunteers emphasize the importance of considering symptom-based subgroups and baseline levels of activity in future investigations of neural activation in schizophrenia.

  18. Increased neural responses to empathy for pain might explain how acute stress increases prosociality.

    Science.gov (United States)

    Tomova, L; Majdandžic, J; Hummer, A; Windischberger, C; Heinrichs, M; Lamm, C

    2017-03-01

    Recent behavioral investigations suggest that acute stress can increase prosocial behavior. Here, we investigated whether increased empathy represents a potential mechanism for this finding. Using functional magnetic resonance imaging, we assessed the effects of acute stress on neural responses related to automatic and regulatory components of empathy for pain as well as subsequent prosocial behavior. Stress increased activation in brain areas associated with the automatic sharing of others' pain, such as the anterior insula, the anterior midcingulate cortex, and the primary somatosensory cortex. In addition, we found increased prosocial behavior under stress. Furthermore, activation in the anterior midcingulate cortex mediated the effects of stress on prosocial behavior. However, stressed participants also displayed stronger and inappropriate other-related responses in situations which required them to take the perspective of another person, and to regulate their automatic affective responses. Thus, while acute stress may increase prosocial behavior by intensifying the sharing of others' emotions, this comes at the cost of reduced cognitive appraisal abilities. Depending on the contextual constraints, stress may therefore affect empathy in ways that are either beneficial or detrimental. © The Author (2016). Published by Oxford University Press.

  19. Acute psychosocial stress does not increase dysfunctional attitudes.

    Science.gov (United States)

    Yeoh, Su Ying; Wilkinson, Paul

    2014-11-01

    Dysfunctional attitudes about oneself, the world and the future, measured quantitatively by Weissman's Dysfunctional Attitudes Scale (DAS), are thought to influence the onset and persistence of major depressive disorder. However, never-depressed individuals may also harbour latent negative schema which may become activated under stressful conditions, giving rise to dysfunctional negative cognitions. This study investigated whether everyday psychosocial stresses could be sufficient to activate dysfunctional self-schema and increase negative cognitions in a large group of healthy adolescents and a preliminary cohort of previously depressed adolescents. 92 never-depressed adolescents aged 17-19 and 18 previously depressed adolescents, recruited from the Cambridge ROOTS cohort, took either version A or B of the DAS at rest on day 1. On day 2, they were subjected to the Trier Social Stress Test, a psychosocial stress paradigm, 22 minutes after which they took the other version of DAS. Stress did not affect the DAS score in either group. Brief psychosocial stress does not appear to influence negative assumptions in healthy young adults with or without a past history of depression. It is possible that this is because dysfunctional assumptions, unlike self-schemas, are not latent. More long-term stresses may be needed to activate negative thoughts to a level where risk of depression is increased.

  20. Parental stress and air pollution increase childhood asthma in China.

    Science.gov (United States)

    Deng, Qihong; Deng, Linjing; Lu, Chan; Li, Yuguo; Norbäck, Dan

    2018-08-01

    Although air pollution and social stress may independently increase childhood asthma, little is known on their synergistic effect on asthma, particularly in China with high levels of stress and air pollution. To examine associations between exposure to a combination of parental stress and air pollution and asthma prevalence in children. We conducted a cohort study of 2406 preschool children in Changsha (2011-2012). A questionnaire was used to collect children's lifetime prevalence of asthma and their parental stress. Parental socioeconomic and psychosocial stresses were respectively defined in terms of housing size and difficulty concentrating. Children's exposure to ambient air pollutants was estimated using concentrations measured at monitoring stations. Associations between exposure to parental stress and air pollution and childhood asthma were estimated by multiple logistic regression models using odds ratio (OR) and 95% confidence interval (CI). Life time prevalence of asthma in preschool children (6.7%) was significantly associated with parental socioeconomic and psychosocial stresses with OR (95% CI) respectively 1.48 (1.02-2.16) and 1.64 (1.00-2.71). Asthma was also associated with exposure to air pollutants, with adjusted OR (95% CI) during prenatal and postnatal periods respectively 1.43 (1.10-1.86) and 1.35 (1.02-1.79) for SO 2 and 1.61 (1.19-2.18) and 1.76 (1.19-2.61) for NO 2 . The association with air pollution was significant only in children exposed to high parental stress, the association with parental stress was significant only in children exposed to high air pollution, and the association was the strongest in children exposed to a combination of parental stress and air pollution. Sensitivity analysis showed that the synergistic effects of parental stress and air pollution on childhood asthma were stronger in boys. Parental stress and air pollution were synergistically associated with increased childhood asthma, indicating a common biological

  1. Can stress in farm animals increase food safety risk?

    Science.gov (United States)

    Rostagno, Marcos H

    2009-09-01

    All farm animals will experience some level of stress during their lives. Stress reduces the fitness of an animal, which can be expressed through failure to achieve production performance standards, or through disease and death. Stress in farm animals can also have detrimental effects on the quality of food products. However, although a common assumption of a potential effect of stress on food safety exists, little is actually known about how this interaction may occur. The aim of this review was to examine the current knowledge of the potential impact of stress in farm animals on food safety risk. Colonization of farm animals by enteric pathogens such as Escherichia coli O157:H7, Salmonella, and Campylobacter, and their subsequent dissemination into the human food chain are a major public health and economic concern for the food industries. This review shows that there is increasing evidence to demonstrate that stress can have a significant deleterious effect on food safety through a variety of potential mechanisms. However, as the impact of stress is difficult to precisely determine, it is imperative that the issue receives more research attention in the interests of optimizing animal welfare and minimizing losses in product yield and quality, as well as to food safety risks to consumers. While there is some evidence linking stress with pathogen carriage and shedding in farm animals, the mechanisms underlying this effect have not been fully elucidated. Understanding when pathogen loads on the farm are the highest or when animals are most susceptible to infection will help identifying times when intervention strategies for pathogen control may be most effective, and consequently, increase the safety of food of animal origin.

  2. Medial Amygdala and Aggressive Behavior : Interaction Between Testosterone and Vasopressin

    NARCIS (Netherlands)

    Koolhaas, J.M.; Roozendaal, B.; Boorsma, F.; Van Den Brink, T.H.C.

    1990-01-01

    This paper considers the functional significance of the testosterone-dependent vasopressinergic neurons of the medial amygdala (Ame) in intermale aggressive behavior of rats. Local microinfusion of vasopressin into the medial amygdala causes an increase in offensive behavior both in gonadally intact

  3. Emotions and stress increase respiratory resistance in asthma.

    Science.gov (United States)

    Ritz, T; Steptoe, A; DeWilde, S; Costa, M

    2000-01-01

    Clinical reports suggest that various emotions and types of stress can precipitate asthmatic symptoms, but there is little experimental evidence to substantiate this claim. We studied the impact of different emotional states and stress on respiratory resistance in asthmatic and nonasthmatic individuals. Participants (24 asthmatic and 24 nonasthmatic patients) viewed short film sequences selected to induce anxiety, anger, depression, elation, happiness, contentment, or a neutral affective state and completed two stressful tasks, mental arithmetic to induce active coping efforts and viewing of medical slides to induce passive coping efforts. Oscillatory resistance, heart rate, blood pressure, baroreflex sensitivity, skin conductance level, respiration rate and volume, and self-reported affective state were measured throughout the session. Uniform increases in oscillatory resistance were found in all emotional states compared with the neutral state and during mental arithmetic in both groups. Asthmatic patients showed stronger reactions to the medical slides than healthy control subjects, with significant increases in oscillatory resistance, blood pressure, skin conductance level, and minute volume, as well as higher levels of self-reported depression, arousal, and shortness of breath. Changes in oscillatory resistance were inconsistently correlated with other physiological indices. Various emotional states and stress increase oscillatory resistance largely independently of concurrent increases in autonomic or ventilatory activity. The particular sensitivity of asthmatics to passive coping demand requires additional research.

  4. [Increase in number of operations for stress urinary incontinence

    NARCIS (Netherlands)

    Vierhout, M.E.

    2005-01-01

    Since the introduction of the minimally invasive tension-free vaginal tape (TVT) the number of operations performed for treatment of stress urinary incontinence has increased dramatically from over 1600 in 1999 to more than 4200 in 2003. Both gynaecologists and urologists now perform more TVTs and

  5. Framing effect following bilateral amygdala lesion.

    Science.gov (United States)

    Talmi, Deborah; Hurlemann, René; Patin, Alexandra; Dolan, Raymond J

    2010-05-01

    A paradigmatic example of an emotional bias in decision making is the framing effect, where the manner in which a choice is posed--as a potential loss or a potential gain--systematically biases an ensuing decision. Two fMRI studies have shown that the activation in the amygdala is modulated by the framing effect. Here, contrary to an expectation based on these studies, we show that two patients with Urbach-Wiethe (UW) disease, a rare condition associated with congenital, complete bilateral amygdala degeneration, exhibit an intact framing effect. However, choice preference in these patients did show a qualitatively distinct pattern compared to controls evident in an increased propensity to gamble, indicating that loss of amygdala function does exert an overall influence on risk-taking. These findings suggest either that amygdala does contribute to decision making but does not play a causal role in framing, or that UW is not a pure lesion model of amygdala function. 2010 Elsevier Ltd. All rights reserved.

  6. MINDFULNESS – MAY DIMINISH STRESS AND INCREASE ENERGY

    Directory of Open Access Journals (Sweden)

    Andronicus TORP

    2015-06-01

    Full Text Available Mindfulness is increasingly being applied in companies as a means to increase, among others, employee wellbeing and energy, and in the same time to diminish stress. This paper argues that there seems to be scientific evidence showing that certain mindfulness techniques may diminish stress and increase energy, yet it seems that there is a period in the beginning of the mindfulness practice where the techniques have the opposite effects. These findings seem to be contradictory to past findings, which indicated that only two thirds of people practicing mindfulness techniques have positive effects from that practice. It may be that everybody can have positive effects from the practice of the mentioned techniques, just that some need to practice for a longer period before obtaining these positive effects. Further scientific studies seem to be needed in order to clarify the full spectrum of effects and consequences of practicing different mindfulness techniques, and just as important, if these effects are valid for everybody.

  7. Input from the medial geniculate nucleus modulates amygdala encoding of fear memory discrimination.

    Science.gov (United States)

    Ferrara, Nicole C; Cullen, Patrick K; Pullins, Shane P; Rotondo, Elena K; Helmstetter, Fred J

    2017-09-01

    Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity as a critical component underlying generalization. The amygdala receives input from auditory cortex as well as the medial geniculate nucleus (MgN) of the thalamus, and these synapses undergo plastic changes in response to fear conditioning and are major contributors to the formation of memory related to both safe and threatening cues. The requirement for MgN protein synthesis during auditory discrimination and generalization, as well as the role of MgN plasticity in amygdala encoding of discrimination or generalization, have not been directly tested. GluR1 and GluR2 containing AMPA receptors are found at synapses throughout the amygdala and their expression is persistently up-regulated after learning. Some of these receptors are postsynaptic to terminals from MgN neurons. We found that protein synthesis-dependent plasticity in MgN is necessary for elevated freezing to both aversive and safe auditory cues, and that this is accompanied by changes in the expressions of AMPA receptor and synaptic scaffolding proteins (e.g., SHANK) at amygdala synapses. This work contributes to understanding the neural mechanisms underlying increased fear to safety signals after stress. © 2017 Ferrara et al.; Published by Cold Spring Harbor Laboratory Press.

  8. The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective.

    Science.gov (United States)

    Gerritsen, L; Kalpouzos, G; Westman, E; Simmons, A; Wahlund, L O; Bäckman, L; Fratiglioni, L; Wang, H X

    2015-04-01

    Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults. In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning. Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women. These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.

  9. Activation of NF-κB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning.

    Science.gov (United States)

    Si, Jijian; Yang, Jianli; Xue, Lifen; Yang, Chenhao; Luo, Yixiao; Shi, Haishui; Lu, Lin

    2012-01-01

    Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA), but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC). We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.

  10. The interplay between the hippocampus and the amygdala in regulating aberrant hippocampal neurogenesis during protracted abstinence from alcohol dependence

    Directory of Open Access Journals (Sweden)

    Chitra D Mandyam

    2013-06-01

    Full Text Available The development of alcohol dependence involves elevated anxiety, low mood, and increased sensitivity to stress, collectively labeled negative affect. Particularly interesting is the recent accumulating evidence that sensitized extrahypothalamic stress systems (e.g., hyperglutamatergic activity, blunted hypothalamic-pituitary-adrenal [HPA] hormonal levels, altered corticotropin-releasing factor signaling, and altered glucocorticoid receptor signaling in the extended amygdala are evident in withdrawn dependent rats, supporting the hypothesis that pathological neuroadaptations in the extended amygdala contribute to the negative affective state. Notably, hippocampal neurotoxicity observed as aberrant dentate gyrus (DG neurogenesis (neurogenesis is a process where neural stem cells in the adult hippocampal subgranular zone generate DG granule cell neurons and DG neurodegeneration are observed in withdrawn dependent rats. These correlations between withdrawal and aberrant neurogenesis in dependent rats suggest that alterations in the DG could be hypothesized to be due to compromised HPA axis activity and associated hyperglutamatergic activity originating from the basolateral amygdala in withdrawn dependent rats. This review discusses a possible link between the neuroadaptations in the extended amygdala stress systems and the resulting pathological plasticity that could facilitate recruitment of new emotional memory circuits in the hippocampus as a function of aberrant DG neurogenesis.

  11. Activation of NF-κB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning.

    Directory of Open Access Journals (Sweden)

    Jijian Si

    Full Text Available Posttraumatic stress disorder (PTSD is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA, but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC. We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.

  12. Sleep spindles predict stress-related increases in sleep disturbances

    Directory of Open Access Journals (Sweden)

    Thien Thanh eDang-Vu

    2015-02-01

    Full Text Available Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. Methods: 12 healthy students had a polysomnography (PSG recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the Insomnia Severity Index (ISI. They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration and frequency, as well as sigma power were computed from C4-O2 electroencephalography (EEG derivation during stages N2-N3 of non-rapid-eye-movement (NREM sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester.Results: Spindle density (as well as spindle amplitude and sigma power, particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05. Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

  13. Involvement of the amygdala in memory storage: Interaction with other brain systems

    Science.gov (United States)

    McGaugh, James L.; Cahill, Larry; Roozendaal, Benno

    1996-01-01

    There is extensive evidence that the amygdala is involved in affectively influenced memory. The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions. Several lines of evidence support this view. First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving the amygdala. In rats, lesions of the amygdala and the stria terminalis block the effects of posttraining administration of epinephrine and glucocorticoids on memory. Furthermore, memory is enhanced by posttraining intra-amygdala infusions of drugs that activate β-adrenergic and glucocorticoid receptors. Additionally, infusion of β-adrenergic blockers into the amygdala blocks the memory-modulating effects of epinephrine and glucocorticoids, as well as those of drugs affecting opiate and GABAergic systems. Second, an intact amygdala is not required for expression of retention. Inactivation of the amygdala prior to retention testing (by posttraining lesions or drug infusions) does not block retention performance. Third, findings of studies using human subjects are consistent with those of animal experiments. β-Blockers and amygdala lesions attenuate the effects of emotional arousal on memory. Additionally, 3-week recall of emotional material is highly correlated with positron-emission tomography activation (cerebral glucose metabolism) of the right amygdala during encoding. These findings provide strong evidence supporting the hypothesis that the amygdala is involved in modulating long-term memory storage. PMID:8942964

  14. Amygdala signals subjective appetitiveness and aversiveness of mixed gambles

    DEFF Research Database (Denmark)

    Gelskov, Sofie V.; Henningsson, Susanne; Madsen, Kristoffer Hougaard

    2015-01-01

    People are more sensitive to losses than to equivalent gains when making financial decisions. We used functional magnetic resonance imaging (fMRI) to illuminate how the amygdala contributes to loss aversion. The blood oxygen level dependent (BOLD) response of the amygdala was mapped while healthy...... individuals were responding to 50/50 gambles with varying potential gain and loss amounts. Overall, subjects demanded twice as high potential gain as loss to accept a gamble. The individual level of loss aversion was expressed by the decision boundary, i.e., the gain-loss ratio at which subjects accepted...... and rejected gambles with equal probability. Amygdala activity increased the more the gain-loss ratio deviated from the individual decision boundary showing that the amygdala codes action value. This response pattern was more strongly expressed in loss aversive individuals, linking amygdala activity...

  15. Resilience and amygdala function in older healthy and depressed adults.

    Science.gov (United States)

    Leaver, Amber M; Yang, Hongyu; Siddarth, Prabha; Vlasova, Roza M; Krause, Beatrix; St Cyr, Natalie; Narr, Katherine L; Lavretsky, Helen

    2018-04-25

    Previous studies suggest that low emotional resilience may correspond with increased or over-active amygdala function. Complementary studies suggest that emotional resilience increases with age; older adults tend to have decreased attentional bias to negative stimuli compared to younger adults. Amygdala nuclei and related brain circuits have been linked to negative affect, and depressed patients have been demonstrated to have abnormal amygdala function. In the current study, we correlated psychological resilience measures with amygdala function measured with resting-state arterial spin-labelled (ASL) and blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in older adults with and without depression. Specifically, we targeted the basolateral, centromedial, and superficial nuclei groups of the amygdala, which have different functions and brain connections. High levels of psychological resilience correlated with lower basal levels of amygdala activity measured with ASL fMRI. High resilience also correlated with decreased connectivity between amygdala nuclei and the ventral default-mode network independent of depression status. Instead, lower depression symptoms were associated with higher connectivity between the amygdalae and dorsal frontal networks. Future multi-site studies with larger sample size and improved neuroimaging technologies are needed. Longitudinal studies that target resilience to naturalistic stressors will also be a powerful contribution to the field. Our results suggest that resilience in older adults is more closely related to function in ventral amygdala networks, while late-life depression is related to reduced connectivity between the amygdala and dorsal frontal regions. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Exposure of rat hippocampal astrocytes to Ziram increases oxidative stress.

    Science.gov (United States)

    Matei, Ann-Marie; Trombetta, Louis D

    2016-04-01

    Pesticides have been shown in several studies to be the leading candidates of environmental toxins and may contribute to the pathogenesis of several neurodegenerative diseases. Ziram (zinc-bis(dimethyldithiocarbamate)) is an agricultural dithiocarbamate fungicide that is used to treat a variety of plant diseases. In spite of their generally acknowledged low toxicity, dithiocarbamates are known to cause a wide range of neurobehavioral effects as well as neuropathological changes in the brain. Astrocytes play a key role in normal brain physiology and in the pathology of the nervous system. This investigation studied the effects of 1.0 µM Ziram on rat hippocampal astrocytes. The thiobarbituric acid reactive substance assay performed showed a significant increase in malondialdehyde, a product of lipid peroxidation, in the Ziram-treated cells. Biochemical analysis also revealed a significant increase in the induction of 70 kDa heat shock and heme oxygenase 1 stress proteins. In addition, an increase of glutathione peroxidase (GPx) and a significant increase in oxidized glutathione (GSSG) were observed in the Ziram-treated cells. The ratio GSH to GSSG calculated from the treated cells was also decreased. Light and transmission electron microscopy supported the biochemical findings in Ziram-treated astrocytes. This data suggest that the cytotoxic effects observed with Ziram treatments may be related to the increase of oxidative stress. © The Author(s) 2013.

  17. Desipramine and citalopram attenuate pretest swim-induced increases in prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis and the lateral division of the central nucleus of the amygdala in the forced swimming test.

    Science.gov (United States)

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Cho, Jin Hee; Cho, Yun Ha; Kim, Dong-Hoon; Shin, Kyung Ho

    2014-10-01

    Dynorphin in the nucleus accumbens shell plays an important role in antidepressant-like effect in the forced swimming test (FST), but it is unclear whether desipramine and citalopram treatments alter prodynorphin levels in other brain areas. To explore this possibility, we injected mice with desipramine and citalopram 0.5, 19, and 23 h after a 15-min pretest swim and observed changes in prodynorphin expression before the test swim, which was conducted 24 h after the pretest swim. The pretest swim increased prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis (dBNST) and lateral division of the central nucleus of the amygdala (CeL). This increase in prodynorphin immunoreactivity in the dBNST and CeL was blocked by desipramine and citalopram treatments. Similar changes in prodynorphin mRNA levels were observed in the dBNST and CeL, but these changes did not reach significance. To understand the underlying mechanism, we assessed changes in phosphorylated CREB at Ser(133) (pCREB) immunoreactivity in the dBNST and central nucleus of the amygdala (CeA). Treatment with citalopram but not desipramine after the pretest swim significantly increased pCREB immunoreactivity only in the dBNST. These results suggest that regulation of prodynorphin in the dBNST and CeL before the test swim may be involved in the antidepressant-like effect of desipramine and citalopram in the FST and suggest that changes in pCREB immunoreactivity in these areas may not play an important role in the regulation of prodynorphin in the dBNST and CeA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The amygdala, reward and emotion.

    Science.gov (United States)

    Murray, Elisabeth A

    2007-11-01

    Recent research provides new insights into amygdala contributions to positive emotion and reward. Studies of neuronal activity in the monkey amygdala and of autonomic responses mediated by the monkey amygdala show that, contrary to a widely held view, the amygdala is just as important for processing positive reward and reinforcement as it is for negative. In addition, neuropsychological studies reveal that the amygdala is essential for only a fraction of what might be considered 'stimulus-reward processing', and that the neural substrates for emotion and reward are partially nonoverlapping. Finally, evidence suggests that two systems within the amygdala, operating in parallel, enable reward-predicting cues to influence behavior; one mediates a general, arousing effect of reward and the other links the sensory properties of reward to emotion.

  19. Increased gluconeogenesis in rats exposed to hyper-G stress

    International Nuclear Information System (INIS)

    Daligcon, B.C.; Oyama, J.; Hannak, K.

    1985-01-01

    The role of gluconeogenesis on the increase in plasma glucose and liver glycogen of rats exposed to hyper-G (radial acceleration) stress was determined. Overnight-fasted, male Sprague-Dawley rats (250-300 g) were injected i.p. with uniformly labeled 14 C lactate, alanine, or glycerol (5 μCi/rat) and immediately exposed to 3.1 G for 0.25, 0.50, and 1.0 hr. 14 C incorporation of the labeled substrates into plasma glucose and liver glycogen was measured and compared to noncentrifuged control rats injected in a similar manner. Significant increases in 14 C incorporation of all three labeled substrates into plasma glucose were observed in centrifuged rats at all exposure periods; 14 C incorporation into liver glycogen was significantly increased only at 0.50 and 1.0 hr. The i.p. administration (5 mg/100-g body wt) of 5-methoxyindole-2-carboxylic acid, a potent gluconeogenesis inhibitor, prior to centrifugation blocked the increase in plasma glucose and liver glycogen during the first hour of centrifugation. The increase in plasma glucose and liver glycogen was also abolished in adrenodemedullated rats exposed to centrifugation for 1.0 hr. Propranolol, a beta-adrenergic blocker, suppressed the increase in plasma glucose of rats exposed to centrifugation for 0.25 hr. From the results of this study, it is concluded that the initial, rapid rise in plasma glucose as well as the increase in liver glycogen of rats exposed to hyper-G stress can be attributed to an increased rate of gluconeogenesis, and that epinephrine plays a dominant role during the early stages of exposure to centrifugation. 11 references, 3 tables

  20. Localization of deformations within the amygdala in individuals with psychopathy.

    Science.gov (United States)

    Yang, Yaling; Raine, Adrian; Narr, Katherine L; Colletti, Patrick; Toga, Arthur W

    2009-09-01

    Despite the repeated findings of impaired fear conditioning and affective recognition in psychopathic individuals, there has been a paucity of brain imaging research on the amygdala and no evidence suggesting which regions within the amygdala may be structurally compromised in individuals with psychopathy. To detect global and regional anatomical abnormalities in the amygdala in individuals with psychopathy. Cross-sectional design using structural magnetic resonance imaging. Participants were recruited from high-risk communities (temporary employment agencies) in the Los Angeles, California, area and underwent imaging at a hospital research facility at the University of Southern California. Twenty-seven psychopathic individuals as defined by the Hare Psychopathy Checklist-Revised and 32 normal controls matched on age, sex, and ethnicity. Amygdala volumes were examined using traditional volumetric analyses and surface-based mesh modeling methods were used to localize regional surface deformations. Individuals with psychopathy showed significant bilateral volume reductions in the amygdala compared with controls (left, 17.1%; right, 18.9%). Surface deformations were localized in regions in the approximate vicinity of the basolateral, lateral, cortical, and central nuclei of the amygdala. Significant correlations were found between reduced amygdala volumes and increased total and facet psychopathy scores, with correlations strongest for the affective and interpersonal facets of psychopathy. Results provide the first evidence, to our knowledge, of focal amygdala abnormalities in psychopathic individuals and corroborate findings from previous lesion studies. Findings support prior hypotheses of amygdala deficits in individuals with psychopathy and indicate that amygdala abnormalities contribute to emotional and behavioral symptoms of psychopathy.

  1. Optogenetic dissection of amygdala functioning

    Directory of Open Access Journals (Sweden)

    Ryan eLalumiere

    2014-03-01

    Full Text Available Studies of amygdala functioning have occupied a significant place in the history of understanding how the brain controls behavior and cognition. Early work on the amygdala placed this small structure as a key component in the regulation of emotion and affective behavior. Over time, our understanding of its role in brain processes has expanded, as we have uncovered amygdala influences on memory, reward behavior, and overall functioning in many other brain regions. Studies have indicated that the amygdala has widespread connections with a variety of brain structures, from the prefrontal cortex to regions of the brainstem, that explain its powerful influence on other parts of the brain and behaviors mediated by those regions. Thus, many optogenetic studies have focused on harnessing the powers of this technique to elucidate the functioning of the amygdala in relation to motivation, fear, and memory as well as to determine how the amygdala regulates activity in other structures. For example, studies using optogenetics have examined how specific circuits within amygdala nuclei regulate anxiety. Other work has provided insight into how the basolateral and central amygdala nuclei regulate memory processing underlying aversive learning. Many experiments have taken advantage of optogenetics’ ability to target either genetically distinct subpopulations of neurons or the specific projections from the amygdala to other brain regions. Findings from such studies have provided evidence that particular patterns of activity in basolateral amygdala glutamatergic neurons are related to memory consolidation processes, while other work has indicated the critical nature of amygdala inputs to the prefrontal cortex and nucleus accumbens in regulating behavior dependent on those downstream structures. This review will examine the recent discoveries on amygdala functioning made through experiments using optogenetics, placing these findings in the context of the major

  2. Activation of corticotropin-releasing factor receptors from the basolateral or central amygdala increases the tonic immobility response in guinea pigs: an innate fear behavior.

    Science.gov (United States)

    Donatti, Alberto Ferreira; Leite-Panissi, Christie Ramos Andrade

    2011-11-20

    The tonic immobility (TI) behavior is an innate response associated with extreme threat situations such as a predator attack. Several studies have provided evidence suggesting an important role for corticotropin-releasing factor (CRF) in the regulation of the endocrine system, defensive behaviors and behavioral responses to stress. TI has been shown to be positively correlated with the basal plasma levels of corticosterone. CRF receptors and neurons that are immunoreactive to CRF are found in many cerebral regions, especially in the amygdaloid complex. Previous reports have demonstrated the involvement of the basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI response. In this study, we evaluated the CRF system of the BLA and the CeA in the modulation of the TI response in guinea pigs. The activation of CRF receptors in the BLA and in the CeA promoted an increase in the TI response. In contrast, the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the duration of the TI response. Moreover, neither the activation nor inhibition of CRF receptors in the BLA or the CeA altered spontaneous motor activity in the open-field test. These data suggest that the activation of the CRF receptors in the BLA or the CeA probably potentiates fear and anxiety, which may be one of the factors that promote an increase in the TI behavior. Therefore, these data support the role of the CRF system in the control of emotional responses, particularly in the modulation of innate fear. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. 杏仁核内去甲肾上腺素在应激激素调控记忆保持过程中的作用%Role of amygdala norepinephrine in mediating stress hormone regu-lation of memory storage

    Institute of Scientific and Technical Information of China (English)

    Barbara FERRY; James L McGAUGH

    2000-01-01

    There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the basolateral nucleus of the amygdala (BLA), is involved in memory consolidation. This article reviews the central hypothesis that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from expenments using rats have shown that the memory-modulatory effects of the adrenocortical stress hormones epinephrine and glucocorficoids involve activation of β-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates memory storage in other brain regions.

  4. [Emotional stress-induced Shanghuo syndrome increases disease susceptibility].

    Science.gov (United States)

    Zhu, Si-Rui; Luo, Xiang; Li, Yi-Fang; Hiroshi, Kurihara; He, Rong-Rong

    2018-04-01

    Shanghuo(excessive internal heat) is a special organic state based on the concept of traditional Chinese medicine(TCM), commonly known as the abnormal heating syndrome of body in folks. With the acceleration of modern life rhythm and the increase of the social competition pressure, emotional stress has become an important cause for the spread of Shanghuo symptoms. What's more, Shanghuo can impact the body physiological functions to cause the onset, recurrence and progression of common diseases, harming the health of the body. According to the long-term research findings, the author found that Shanghuo referred to the imbalance of multiple physiological functions, such as nerve, immunity and metabolism, caused by emotional stress. "Shanghuo" is not a disease itself, but it can increase the susceptibility to a variety of diseases. This study reviewed the traditional medicine theory and the modern medical studies, and explored the relevance and correlation mechanisms between the Shanghuo symptoms and disease susceptibility, so as to provide a reference to improve the state of sub-health and prevent or treat modern diseases. Copyright© by the Chinese Pharmaceutical Association.

  5. Nest ectoparasites increase physiological stress in breeding birds: an experiment.

    Science.gov (United States)

    Martínez-de la Puente, Josué; Merino, Santiago; Tomás, Gustavo; Moreno, Juan; Morales, Judith; Lobato, Elisa; Martínez, Javier

    2011-02-01

    Parasites are undoubtedly a biotic factor that produces stress. Heat shock proteins (HSPs) are important molecules buffering cellular damage under adverse conditions. During the breeding season, blue tit Cyanistes caeruleus (L.) adults are affected by blood parasites, nest-dwelling parasites and biting flies, potentially affecting their HSP-mediated responses. Here, we treated females with primaquine to reduce blood parasites and fumigated nests with permethrin to reduce nest-dwelling parasites to test whether these treatments affect HSP60 level during the breeding season. Medicated females, but not controls, had a significant reduction of the intensity of infection by Haemoproteus spp. blood parasites. However, final intensity of infection did not differ significantly between groups, and we did not find an effect of medication on change in HSP60 level. Fumigation reduced the abundance of nest-dwelling parasites (mites, fleas and blowfly larvae) and engorged biting midges in nests. Females breeding in non-fumigated nests increased HSP60 levels during the season more than those breeding in fumigated nests. Furthermore, the change in HSP60 level was positively correlated with the abundance of biting midges. These results show how infections by nest ectoparasites during the breeding period can increase the level of HSPs and suggest that biting midges impose physiological costs on breeding female blue tits. Although plausible, the alternative that biting midges prefer to feed on more stressed birds is poorly supported by previous studies.

  6. Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder.

    Science.gov (United States)

    Young, Kymberly D; Siegle, Greg J; Misaki, Masaya; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

    2018-01-01

    We have previously shown that in participants with major depressive disorder (MDD) trained to upregulate their amygdala hemodynamic response during positive autobiographical memory (AM) recall with real-time fMRI neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. Here, we assessed the effect of rtfMRI-nf on amygdala functional connectivity during both positive AM recall and rest. The current manuscript consists of a secondary analysis on data from our published clinical trial of neurofeedback. Patients with MDD completed two rtfMRI-nf sessions (18 received amygdala rtfMRI-nf, 16 received control parietal rtfMRI-nf). One-week prior-to and following training participants also completed a resting-state fMRI scan. A GLM-based functional connectivity analysis was applied using a seed ROI in the left amygdala. We compared amygdala functional connectivity changes while recalling positive AMs from the baseline run to the final transfer run during rtfMRI-nf training, as well during rest from the baseline to the one-week follow-up visit. Finally, we assessed the correlation between change in depression scores and change in amygdala connectivity, as well as correlations between amygdala regulation success and connectivity changes. Following training, amygdala connectivity during positive AM recall increased with widespread regions in the frontal and limbic network. During rest, amygdala connectivity increased following training within the fronto-temporal-limbic network. During both task and resting-state analyses, amygdala-temporal pole connectivity decreased. We identified increased amygdala-precuneus and amygdala-inferior frontal gyrus connectivity during positive memory recall and increased amygdala-precuneus and amygdala-thalamus connectivity during rest as functional connectivity changes that explained significant variance in symptom improvement. Amygdala-precuneus connectivity changes also explain a significant amount of variance in neurofeedback

  7. Contribution of amygdala CRF neurons to chronic pain.

    Science.gov (United States)

    Andreoli, Matthew; Marketkar, Tanvi; Dimitrov, Eugene

    2017-12-01

    We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over

  8. Neurons in the human amygdala selective for perceived emotion

    Science.gov (United States)

    Wang, Shuo; Tudusciuc, Oana; Mamelak, Adam N.; Ross, Ian B.; Adolphs, Ralph; Rutishauser, Ueli

    2014-01-01

    The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We investigated these questions by recording from over 200 single neurons in the amygdalae of 7 neurosurgical patients with implanted depth electrodes. We presented degraded fear and happy faces and asked subjects to discriminate their emotion by button press. During trials where subjects responded correctly, we found neurons that distinguished fear vs. happy emotions as expressed by the displayed faces. During incorrect trials, these neurons indicated the patients’ subjective judgment. Additional analysis revealed that, on average, all neuronal responses were modulated most by increases or decreases in response to happy faces, and driven predominantly by judgments about the eye region of the face stimuli. Following the same analyses, we showed that hippocampal neurons, unlike amygdala neurons, only encoded emotions but not subjective judgment. Our results suggest that the amygdala specifically encodes the subjective judgment of emotional faces, but that it plays less of a role in simply encoding aspects of the image array. The conscious percept of the emotion shown in a face may thus arise from interactions between the amygdala and its connections within a distributed cortical network, a scheme also consistent with the long response latencies observed in human amygdala recordings. PMID:24982200

  9. Parent-child intervention decreases stress and increases maternal brain activity and connectivity during own baby-cry: An exploratory study.

    Science.gov (United States)

    Swain, James E; Ho, S Shaun; Rosenblum, Katherine L; Morelen, Diana; Dayton, Carolyn J; Muzik, Maria

    2017-05-01

    Parental responses to their children are crucially influenced by stress. However, brain-based mechanistic understanding of the adverse effects of parenting stress and benefits of therapeutic interventions is lacking. We studied maternal brain responses to salient child signals as a function of Mom Power (MP), an attachment-based parenting intervention established to decrease maternal distress. Twenty-nine mothers underwent two functional magnetic resonance imaging brain scans during a baby-cry task designed to solicit maternal responses to child's or self's distress signals. Between scans, mothers were pseudorandomly assigned to either MP (n = 14) or control (n = 15) with groups balanced for depression. Compared to control, MP decreased parenting stress and increased child-focused responses in social brain areas highlighted by the precuneus and its functional connectivity with subgenual anterior cingulate cortex, which are key components of reflective self-awareness and decision-making neurocircuitry. Furthermore, over 13 weeks, reduction in parenting stress was related to increasing child- versus self-focused baby-cry responses in amygdala-temporal pole functional connectivity, which may mediate maternal ability to take her child's perspective. Although replication in larger samples is needed, the results of this first parental-brain intervention study demonstrate robust stress-related brain circuits for maternal care that can be modulated by psychotherapy.

  10. Increased prevalence of posttraumatic stress disorder in CRPS.

    Science.gov (United States)

    Speck, V; Schlereth, T; Birklein, F; Maihöfner, C

    2017-03-01

    Although specific psychological disorders in complex regional pain syndrome (CRPS) have not been identified, studies suggest that CRPS patients may have increased rates of traumatic life events. Because these events do not always lead to apparent psychological symptoms, we systematically screened CRPS patients for posttraumatic stress disorder (PTSD) to determine if PTSD could be a risk factor for CRPS. Consecutive CRPS patients referred to two university hospital centres (University of Erlangen, UMC Mainz) between December 2011 and April 2013 were prospectively examined using a diagnostic PTSD instrument (Post-traumatic Stress Diagnostic Scale (PDS). We also tested maladaptive coping strategies (brief-COPE inventory) and the PDS severity score as predictors for CRPS. Patients with non-CRPS extremity pain and healthy individuals were used as control groups. We collected data from 152 patients with CRPS, 55 control patients and 55 age- and sex-matched healthy individuals. Fifty-eight CRPS patients (38%), six non-CRPS pain patients (10%) and two healthy individuals (4%) met diagnostic criteria for PTSD. Initial PTSD symptom onset was prior to CRPS in 50 CRPS patients (86%) and during the course of CRPS in eight patients. Results of a logistic regression revealed that the PTSD severity score was associated with CRPS (p CRPS than it is in the general population. Research has not yet provided support for specific psychological predictors for CRPS. © 2016 European Pain Federation - EFIC®.

  11. High lung volume increases stress failure in pulmonary capillaries

    Science.gov (United States)

    Fu, Z.; Costello, M. L.; Tsukimoto, K.; Prediletto, R.; Elliott, A. R.; Mathieu-Costello, O.; West, J. B.

    1992-01-01

    We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological

  12. Mating with stressed males increases the fitness of ant queens.

    Directory of Open Access Journals (Sweden)

    Alexandra Schrempf

    Full Text Available BACKGROUND: According to sexual conflict theory, males can increase their own fitness by transferring substances during copulation that increase the short-term fecundity of their mating partners at the cost of the future life expectancy and re-mating capability of the latter. In contrast, sexual cooperation is expected in social insects. Mating indeed positively affects life span and fecundity of young queens of the male-polymorphic ant Cardiocondyla obscurior, even though males neither provide nuptial gifts nor any other care but leave their mates immediately after copulation and die shortly thereafter. PRINCIPAL FINDINGS: Here, we show that mating with winged disperser males has a significantly stronger impact on life span and reproductive success of young queens of C. obscurior than mating with wingless fighter males. CONCLUSIONS: Winged males are reared mostly under stressful environmental conditions, which force young queens to disperse and found their own societies independently. In contrast, queens that mate with wingless males under favourable conditions usually start reproducing in the safety of the established maternal nest. Our study suggests that males of C. obscurior have evolved mechanisms to posthumously assist young queens during colony founding under adverse ecological conditions.

  13. Can stress increase Alzheimer's disease risk in women?

    Science.gov (United States)

    Johansson, Lena

    2014-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of β-amyloid peptides and neurofibrilllary tangles in brain, resulting in neuronal death and loss of cognitive abilities. It has been hypothesized that longstanding psychological stress can result in neural degeneration and AD due to pathological alterations in the hypothalamic-pituitary-adrenal axis. In recent years several epidemiological studies been published on stress as a risk factor for AD. As women are more likely to suffer from stress-related psychiatric disorders, such as post-traumatic stress disorder and clinical burnout syndrome, special effort has been made according to the gender differences in risk of AD. However, few studies have stratified for gender, due to small sample sizes and limited statistic power, and no reliable findings have been found. Additional longitudinal studies are therefore needed for studying gender differences and for determining what mediates the stress and AD association, in both genders.

  14. Stress in biological invasions: Introduced invasive grey squirrels increase physiological stress in native Eurasian red squirrels.

    Science.gov (United States)

    Santicchia, Francesca; Dantzer, Ben; van Kesteren, Freya; Palme, Rupert; Martinoli, Adriano; Ferrari, Nicola; Wauters, Lucas Armand

    2018-05-23

    Invasive alien species can cause extinction of native species through processes including predation, interspecific competition for resources or disease-mediated competition. Increases in stress hormones in vertebrates may be associated with these processes and contribute to the decline in survival or reproduction of the native species. Eurasian red squirrels (Sciurus vulgaris) have gone extinct across much of the British Isles and parts of Northern Italy following the introduction of North American invasive grey squirrels (Sciurus carolinensis). We extracted glucocorticoid metabolites from faecal samples to measure whether the presence of the invasive species causes an increase in physiological stress in individuals of the native species. We show that native red squirrels in seven sites where they co-occurred with invasive grey squirrels had glucocorticoid concentrations that were three times higher than those in five sites without the invasive species. Moreover, in a longitudinal study, stress hormones in native red squirrels increased after colonisation by grey squirrels. When we experimentally reduced the abundance of the invasive grey squirrels, the concentration of faecal glucocorticoid metabolites in co-occurring red squirrels decreased significantly between pre- and postremoval periods. Hence, we found that the invasive species acts as a stressor which significantly increases the concentrations of glucocorticoids in the native species. Given that sustained elevations in glucocorticoids could reduce body growth and reproductive rate, our results are consistent with previous studies where the co-occurrence of the invasive grey squirrel was associated with smaller size and lower reproductive output in red squirrels. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.

  15. Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls.

    Science.gov (United States)

    Janiri, Delfina; Sani, Gabriele; Rossi, Pietro De; Piras, Fabrizio; Iorio, Mariangela; Banaj, Nerisa; Giuseppin, Giulia; Spinazzola, Edoardo; Maggiora, Matteo; Ambrosi, Elisa; Simonetti, Alessio; Spalletta, Gianfranco

    2017-08-01

    Volumetric studies on deep gray matter structures in bipolar disorder (BP) have reported contrasting results. Childhood trauma, a relevant environmental stressor for BP, could account for the variability of the results, modulating differences in the amygdala and hippocampus in patients with BP compared with healthy controls (HC). Our study aimed to test this hypothesis. We assessed 105 outpatients, diagnosed with bipolar disorder type I (BP-I) or bipolar disorder type II (BP-II) according to DSM-IV-TR criteria, and 113 HC subjects. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). High-resolution magnetic resonance imaging was performed on all subjects and volumes of the amygdala, hippocampus, nucleus accumbens, caudate, pallidum, putamen, and thalamus were measured using FreeSurfer. Patients with BP showed a global reduction of deep gray matter volumes compared to HCs. However, childhood trauma modulated the impact of the diagnosis specifically on the amygdala and hippocampus. Childhood trauma was associated with bilateral decreased volumes in HCs and increased volumes in patients with BP. The results suggest that childhood trauma may have a different effect in health and disease on volumes of gray matter in the amygdala and hippocampus, which are brain areas specifically involved in response to stress and emotion processing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Angiotensin II and CRF Receptors in the Central Nucleus of the Amygdala Mediate Hemodynamic Response Variability to Cocaine in Conscious Rats

    OpenAIRE

    Watanabe, Mari A.; Kucenas, Sarah; Bowman, Tamara A.; Ruhlman, Melissa; Knuepfer, Mark M.

    2009-01-01

    Stress or cocaine evokes either a large increase in systemic vascular resistance (SVR) or a smaller increase in SVR accompanied by an increase in cardiac output (designated vascular and mixed responders, respectively) in Sprague-Dawley rats. We hypothesized that the central nucleus of the amygdala (CeA) mediates this variability. Conscious, freely-moving rats, instrumented for measurement of arterial pressure and cardiac output and for drug delivery into the CeA, were given cocaine (5 mg/kg, ...

  17. Corticosteroid Induced Decoupling of the Amygdala in Men

    NARCIS (Netherlands)

    Henckens, Marloes J. A. G.; van Wingen, Guido A.; Joëls, Marian; Fernández, Guillén

    2012-01-01

    The amygdala is a key regulator of vigilance and heightens attention toward threat. Its activity is boosted upon threat exposure and contributes to a neuroendocrine stress response via the hypothalamic-pituitary-adrenal (HPA) axis. Corticosteroids are known to control brain activity as well as HPA

  18. Activation of protein kinase A in the amygdala modulates anxiety-like behaviors in social defeat exposed mice.

    Science.gov (United States)

    Yang, Liu; Shi, Li-Jun; Yu, Jin; Zhang, Yu-Qiu

    2016-01-08

    Social defeat (SD) stress induces social avoidance and anxiety-like phenotypes. Amygdala is recognized as an emotion-related brain region such as fear, aversion and anxiety. It is conceivable to hypothesize that activation of amygdala is involved in SD-dependent behavioral defects. SD model was established using C57BL/6J mice that were physically defeated by different CD-1 mice for 10 days. Stressed mice exhibited decreased social interaction level in social interaction test and significant anxiety-like behaviors in elevated plus maze and open field tests. Meanwhile, a higher phosphorylation of PKA and CREB with a mutually linear correlation, and increased Fos labeled cells in the basolateral amygdala (BLA) were observed. Activation of PKA in the BLA by 8-Br-cAMP, a PKA activitor, significantly upregulated pCREB and Fos expression. To address the role of PKA activation on SD stress-induced social avoidance and anxiety-like behaviors, 8-Br-cAMP or H-89, a PKA inhibitor, was continuously administered into the bilateral BLA by a micro-osmotic pump system during the 10-day SD period. Neither H-89 nor 8-Br-cAMP affected the social behavior. Differently, 8-Br-cAMP significantly relieved anxiety-like behaviors in both general and moderate SD protocols. H-89 per se did not have anxiogenic effect in naïve mice, but aggravated moderate SD stress-induced anxiety-like behaviors. The antidepressant clomipramine reduced SD-induced anxiety and up-regulated pPKA level in the BLA. These results suggest that SD-driven PKA activation in the basolateral amygdala is actually a compensatory rather than pathogenic response in the homeostasis, and modulating amygdaloid PKA may exhibit potency in the therapy of social derived disorders.

  19. Learner-centred medical education: Improved learning or increased stress?

    Science.gov (United States)

    McLean, Michelle; Gibbs, Trevor J

    2009-12-01

    Globally, as medical education undergoes significant reform towards more "learner-centred" approaches, specific implications arise for medical educators and learners. Although this learner-centredness is grounded in educational theory, a point of discussion would be whether the application and practice of these new curricula alleviate or exacerbate student difficulties and levels of stress. This commentary will argue that while this reform in medical education is laudable, with positive implications for learning, medical educators may not have understood or perhaps not embraced "learner-centredness" in its entirety. During their training, medical students are expected to be "patient-centred". They are asked to apply a biopsychosocial model, which takes cognisance of all aspects of a patient's well-being. While many medical schools profess that their curricula reflect these principles, in reality, many may not always practice what they preach. Medical training all too often remains grounded in the biomedical model, with the cognitive domain overshadowing the psychosocial development and needs of learners. Entrusted by parents and society with the education and training of future healthcare professionals, medical education needs to move to a "learner-centred philosophy", in which the "whole" student is acknowledged. As undergraduate and post-graduate students increasingly apply their skills in an international arena, this learner-centredness should equally encapsulate the gender, cultural and religious diversity of both patients and students. Appropriate support structures, role models and faculty development are required to develop skills, attitudes and professional behaviour that will allow our graduates to become caring and sensitive healthcare providers.

  20. The Development of Human Amygdala Functional Connectivity at Rest from 4 to 23 Years: a cross-sectional study

    Science.gov (United States)

    Gabard-Durnam, Laurel J.; Flannery, Jessica; Goff, Bonnie; Gee, Dylan G.; Humphreys, Kathryn L.; Telzer, Eva; Hare, Todd; Tottenham, Nim

    2014-01-01

    Functional connections (FC) between the amygdala and cortical and subcortical regions underlie a range of affective and cognitive processes. Despite the central role amygdala networks have in these functions, the normative developmental emergence of FC between the amygdala and the rest of the brain is still largely undefined. This study employed amygdala subregion maps and resting-state functional magnetic resonance imaging to characterize the typical development of human amygdala FC from age 4 to 23 years old (n = 58). Amygdala FC with subcortical and limbic regions was largely stable across this developmental period. However, three cortical regions exhibited age-dependent changes in FC: amygdala FC with the medial prefrontal cortex (mPFC) increased with age, while amygdala FC with a region including the insula and superior temporal sulcus decreased with age, and amygdala FC with a region encompassing the parahippocampal gyrus and posterior cingulate also decreased with age. The transition from childhood to adolescence (around age 10 years) marked an important change-point in the nature of amygdala-cortical FC. We distinguished unique developmental patterns of coupling for three amygdala subregions and found particularly robust convergence of FC for all subregions with the mPFC. These findings suggest that there are extensive changes in amygdala-cortical functional connectivity that emerge between childhood and adolescence. PMID:24662579

  1. 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.

  2. Toxoplasma gondii infection induces dendritic retraction in basolateral amygdala accompanied by reduced corticosterone secretion

    Directory of Open Access Journals (Sweden)

    Rupshi Mitra

    2013-03-01

    Pathological anxiety is thought to reflect a maladaptive state characterized by exaggerated fear. Naturally occurring perturbations that reduce fear can be crucial in the search for new treatments. The protozoan parasite Toxoplasma gondii invades rat brain and removes the fear that rats have of cat odors, a change believed to be parasitic manipulation of host behavior aimed at increasing parasite transmission. It is likely that mechanisms employed by T. gondii can be used as a heuristic tool to understand possible means of fear reduction in clinical settings. Male Long-Evans rats were infected with T. gondii and compared with sham-infected animals 8 weeks after infection. The amount of circulating plasma corticosterone and dendritic arborization of basolateral amygdala principal neurons were quantified. Previous studies have shown that corticosterone, acting within the basolateral amygdala, enhances the fear response to environmental stimuli. Here we show that T. gondii infection causes a dendritic retraction in basolateral amygdala neurons. Such dendritic retraction is accompanied by lower amounts of circulating corticosterone, both at baseline and when induced by an aversive cat odor. The concerted effects of parasitism on two pivotal physiological nodes of the fear response provide an animal model relevant to interactions between stress hormones and amygdalar plasticity.

  3. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    OpenAIRE

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease is the largest cause of mortality worldwide, and stress is a significant contributor to the development of cardiovascular disease. The relationship between acute and chronic stress and cardiovascular disease is well-evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury. Conversely, chronic stress is arrythmogenic and incr...

  4. Amygdala temporal dynamics: temperamental differences in the timing of amygdala response to familiar and novel faces

    Directory of Open Access Journals (Sweden)

    Shelton Richard C

    2009-12-01

    Full Text Available Abstract Background Inhibited temperament - the predisposition to respond to new people, places or things with wariness or avoidance behaviors - is associated with increased risk for social anxiety disorder and major depression. Although the magnitude of the amygdala's response to novelty has been identified as a neural substrate of inhibited temperament, there may also be differences in temporal dynamics (latency, duration, and peak. We hypothesized that persons with inhibited temperament would have faster responses to novel relative to familiar neutral faces compared to persons with uninhibited temperament. We used event-related functional magnetic resonance imaging to measure the temporal dynamics of the blood oxygen level dependent (BOLD response to both novel and familiar neutral faces in participants with inhibited or uninhibited temperament. Results Inhibited participants had faster amygdala responses to novel compared with familiar faces, and both longer and greater amygdala response to all faces. There were no differences in peak response. Conclusion Faster amygdala response to novelty may reflect a computational bias that leads to greater neophobic responses and represents a mechanism for the development of social anxiety.

  5. Increased levels of conditioned fear and avoidance behavior coincide with changes in phosphorylation of the protein kinase B (AKT) within the amygdala in a mouse model of extremes in trait anxiety.

    Science.gov (United States)

    Yen, Yi-Chun; Mauch, Christoph P; Dahlhoff, Maik; Micale, Vincenzo; Bunck, Mirjam; Sartori, Simone B; Singewald, Nicolas; Landgraf, Rainer; Wotjak, Carsten T

    2012-07-01

    Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned fear. To gain further insights into the mechanisms underlying these phenomenona, we studied conditioned fear in mice originating form a bi-directional selective breeding approach, which is based on elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxiety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the basolateral amygdala 45 min after conditioning. No similar changes were observed after non-associative immediate shock presentations. Fear extinction of recent but not older fear memories was preserved. However, HAB mice were more prone to relapse of conditioned fear with the passage of time. HAB mice also displayed higher levels of contextual fear compared to NAB and LAB mice and exaggerated avoidance following step-down avoidance training. Interestingly, HAB mice showed lower and LAB mice higher levels of acoustic startle responses compared to NAB controls. The increase in arousal observed in LAB mice coincided with the general absence of conditioned freezing. Taken together, our results suggest that the genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic memories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking behavior seems to be associated with an increase in active coping styles. Our data imply changes in AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Amygdala's involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition.

    Science.gov (United States)

    Chau, Lily S; Galvez, Roberto

    2012-01-01

    It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  7. Primate amygdala neurons evaluate the progress of self-defined economic choice sequences.

    Science.gov (United States)

    Grabenhorst, Fabian; Hernadi, Istvan; Schultz, Wolfram

    2016-10-12

    The amygdala is a prime valuation structure yet its functions in advanced behaviors are poorly understood. We tested whether individual amygdala neurons encode a critical requirement for goal-directed behavior: the evaluation of progress during sequential choices. As monkeys progressed through choice sequences toward rewards, amygdala neurons showed phasic, gradually increasing responses over successive choice steps. These responses occurred in the absence of external progress cues or motor preplanning. They were often specific to self-defined sequences, typically disappearing during instructed control sequences with similar reward expectation. Their build-up rate reflected prospectively the forthcoming choice sequence, suggesting adaptation to an internal plan. Population decoding demonstrated a high-accuracy progress code. These findings indicate that amygdala neurons evaluate the progress of planned, self-defined behavioral sequences. Such progress signals seem essential for aligning stepwise choices with internal plans. Their presence in amygdala neurons may inform understanding of human conditions with amygdala dysfunction and deregulated reward pursuit.

  8. Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Guo, Qinyue; Xu, Lin; Li, Huixia; Sun, Hongzhi; Liu, Jiali; Wu, Shufang; Zhou, Bo

    2017-01-31

    Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed. Progranulin treatment increased iNOS expression, NO synthesis and ROS generation, and elevated protein expressions of CHOP, GRP78 and the phosphorylation of PERK, and caused a significant increase in Atg7 and LC3-II protein expression and a decreased p62 expression, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake, demonstrating that progranulin activated oxidative stress and ER stress, elevated autophagy and induced insulin insensitivity in adipocytes and adipose tissue of mice. Interestingly, inhibition of iNOS and ER stress both reversed progranulin-induced stress response and increased autophagy, protecting against insulin resistance in adipocytes. Furthermore, the administration of the ER stress inhibitor 4-phenyl butyric acid reversed the negative effect of progranulin in vivo. Our findings showed the clinical potential of the novel adipokine progranulin in the regulation of insulin resistance, suggesting that progranulin might mediate adipose insulin resistance, at least in part, by inducing autophagy via activated oxidative stress and ER stress.

  9. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

    Science.gov (United States)

    Koshibu, K; Gräff, J; Mansuy, I M

    2011-01-26

    Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously. Our work recently demonstrated that epigenetic mechanisms in the adult brain are in part regulated by protein phosphatase 1 (PP1), a protein Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures involved in emotional processing like the amygdala, it may therefore be involved in the regulation of fear memory, a form of memory related to post-traumatic stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular suppressor of fear memory and synaptic plasticity in the amygdala that can control chromatin remodeling in neurons. We show that the selective inhibition of the nuclear pool of PP1 in amygdala neurons significantly alters posttranslational modifications (PTMs) of histones and the expression of several memory-associated genes. These alterations correlate with enhanced fear memory, and with an increase in long-term potentiation (LTP) that is transcription-dependent. Our results underscore the importance of nuclear PP1 in the amygdala as an epigenetic regulator of emotional memory, and the relevance of protein phosphatases as potential targets for therapeutic treatment of brain disorders like PTSD. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Biomass production and potential water stress increase with ...

    African Journals Online (AJOL)

    The choice of planting density and tree genotype are basic decisions when establishing a forest stand. Understanding the interaction between planting density and genotype, and their relationship with biomass production and potential water stress, is crucial as forest managers are faced with a changing climate. However ...

  11. PTSD symptom severity is associated with increased recruitment of top-down attentional control in a trauma-exposed sample

    OpenAIRE

    White, Stuart F.; Costanzo, Michelle E.; Blair, James R.; Roy, Michael J.

    2015-01-01

    Background: Recent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a populat...

  12. Sex differences in the functional connectivity of the amygdalae in association with cortisol.

    Science.gov (United States)

    Kogler, Lydia; Müller, Veronika I; Seidel, Eva-Maria; Boubela, Roland; Kalcher, Klaudius; Moser, Ewald; Habel, Ute; Gur, Ruben C; Eickhoff, Simon B; Derntl, Birgit

    2016-07-01

    Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Effects of increased rock strata stresses on coal gettability

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, W; Skoczynski, W [Politechnika Slaska, Gliwice (Poland). Instytut Mechanizacji Gornictwa

    1988-01-01

    Analyzes effects of rock strata pressure on a coal seam, its cracking and on energy consumption of coal cutting by shearer loaders and coal plows. Effects of mining depth on stresses in a coal seam rib side were analyzed using formulae developed by Budryk, Chudek and Borecki. Formulae used for selecting optimum yield strength of powered supports at working faces are reviewed. Four types of spontaneous separation of coal seam blocks caused by rock strata stresses are evaluated: layers parallel to the face with constant thickness, coal blocks with thickness decreasing in the direction of the floor or roof (blocks with a planar triangle cross-cut), blocks situated in the seam layer adjacent to the floor or roof. Causes of each type of coal seam separation are analyzed. 9 refs.

  14. Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function.

    Science.gov (United States)

    Azzinnari, Damiano; Sigrist, Hannes; Staehli, Simon; Palme, Rupert; Hildebrandt, Tobias; Leparc, German; Hengerer, Bastian; Seifritz, Erich; Pryce, Christopher R

    2014-10-01

    In neuropsychiatry, animal studies demonstrating causal effects of environmental manipulations relevant to human aetiology on behaviours relevant to human psychopathologies are valuable. Such valid models can improve understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core symptoms or features. Here we exposed adult male C57BL/6 mice to 15-day psychosocial stress with loss of social control but minimal physical wounding. One cohort was assessed in a 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. Socially stressed mice displayed decreased motor activity, increased fear acquisition, decreased 2-way avoid-escape responding (increased helplessness) and increased fatigue. They also displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy without hyper-corticoidism. In a third cohort, psychosocial stress effects on brain gene expression were assessed using next generation sequencing. Gene expression was altered in pathways of inflammation and G-protein coupled receptors in prefrontal cortex and amygdala; in the latter, expression of genes important in dopamine function were de-regulated including down-regulated Drd2, Adora2a and Darpp-32. This model can be applied to identify targets for treating psychopathologies such as helplessness or fatigue, and to screen compounds/biologics developed to act at these targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis.

    Science.gov (United States)

    Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan

    2017-12-01

    The amygdala is a large grey matter complex in the limbic system, and it may contribute in the neurolimbic pain network in migraine. However, the detailed neuromechanism remained to be elucidated. The objective of this study is to investigate the amygdala structural and functional changes in migraine and to elucidate the mechanism of neurolimbic pain-modulating in the migraine pathogenesis. Conventional MRI, 3D structure images and resting state functional MRI were performed in 18 normal controls (NC), 18 patients with episodic migraine (EM), and 16 patients with chronic migraine (CM). The amygdala volume was measured using FreeSurfer software and the functional connectivity (FC) of bilateral amygdala was computed over the whole brain. Analysis of covariance was performed on the individual FC maps among groups. The increased FC of left amygdala was observed in EM compared with NC, and the decreased of right amygdala was revealed in CM compared with NC. The increased FC of bilateral amygdala was observed in CM compared with EM. The correlation analysis showed a negative correlation between the score of sleep quality (0, normal; 1, mild sleep disturbance; 2, moderate sleep disturbance; 3, serious sleep disturbance) and the increased FC strength of left amygdala in EM compared with NC, and a positive correlation between the score of sleep quality and the increased FC strength of left amygdala in CM compared with EM, and other clinical variables showed no significant correlation with altered FC of amygdala. The altered functional connectivity of amygdala demonstrated that neurolimbic pain network contribute in the EM pathogenesis and CM chronicization.

  16. From circuits to behaviour in the amygdala

    Science.gov (United States)

    Janak, Patricia H.; Tye, Kay M.

    2015-01-01

    The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits. PMID:25592533

  17. Preferential amygdala reactivity to the negative assessment of neutral faces.

    Science.gov (United States)

    Blasi, Giuseppe; Hariri, Ahmad R; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R; Mattay, Venkata S

    2009-11-01

    Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues.

  18. Induced groundwater flux by increases in the aquifer's total stress.

    Science.gov (United States)

    Chang, Ching-Min; Yeh, Hund-Der

    2015-01-01

    Fluid-filled granular soils experience changes in total stress because of earth and oceanic tides, earthquakes, erosion, sedimentation, and changes in atmospheric pressure. The pore volume may deform in response to the changes in stress and this may lead to changes in pore fluid pressure. The transient fluid flow can therefore be induced by the gradient in excess pressure in a fluid-saturated porous medium. This work demonstrates the use of stochastic methodology in prediction of induced one-dimensional field-scale groundwater flow through a heterogeneous aquifer. A closed-form of mean groundwater flux is developed to quantify the induced field-scale mean behavior of groundwater flow and analyze the impacts of the spatial correlation length scale of log hydraulic conductivity and the pore compressibility. The findings provided here could be useful for the rational planning and management of groundwater resources in aquifers that contain lenses with large vertical aquifer matrix compressibility values. © 2014, National Ground Water Association.

  19. Increased oxidative stress in infants exposed to passive smoking.

    Science.gov (United States)

    Aycicek, Ali; Erel, Ozcan; Kocyigit, Abdurrahim

    2005-12-01

    The purpose of this study was to assess the effect of passive cigarette smoking on the oxidative and anti-oxidative status of plasma in infants. Eighty-four infants aged 6-28 weeks were divided into two groups: the study group included infants who had been exposed to passive smoking via at least five cigarettes per day for at least the past 6 weeks at home, while the control group included infants who had never been exposed to passive smoking. The antioxidative status of plasma was assessed by the measurement of individual antioxidant components: vitamin C, albumin, bilirubin, uric acid, thiol contents and total antioxidant capacity (TAC 1 and TAC 2). Oxidative status was assessed by the determination of total peroxide levels and the oxidative stress index (OSI 1 and OSI 2). Plasma vitamin C, thiol concentration and TAC 1 and TAC 2 levels were significantly lower, whereas plasma total peroxide levels and OSI 1 and OSI 2 were significantly higher, in passive smoking infants than in the controls (Pantioxidant defence system in infants, and exposes them to potent oxidative stress.

  20. Arbutin increases Caenorhabditis elegans longevity and stress resistance

    Directory of Open Access Journals (Sweden)

    Lin Zhou

    2017-12-01

    Full Text Available Arbutin (p-hydroxyphenyl-β-D-glucopyranoside, a well-known tyrosinase inhibitor, has been widely used as a cosmetic whitening agent. Although its natural role is to scavenge free radicals within cells, it has also exhibited useful activities for the treatment of diuresis, bacterial infections and cancer, as well as anti-inflammatory and anti-tussive activities. Because function of free radical scavenging is also related to antioxidant and the effects of arbutin on longevity and stress resistance in animals have not yet been confirmed, here the effects of arbutin on Caenorhabditis elegans were investigated. The results demonstrated that optimal concentrations of arbutin could extend lifespan and enhance resistance to oxidative stress. The underlying molecular mechanism for these effects involves decreased levels of reactive oxygen species (ROS, improvement of daf-16 nuclear localization, and up-regulated expression of daf-16 and its downstream targets, including sod-3 and hsp16.2. In this work the roles of arbutin in lifespan and health are studied and the results support that arbutin is an antioxidant for maintaining overall health.

  1. Fear extinction requires infralimbic cortex projections to the basolateral amygdala.

    Science.gov (United States)

    Bloodgood, Daniel W; Sugam, Jonathan A; Holmes, Andrew; Kash, Thomas L

    2018-03-06

    Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear-induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.

  2. Do levels of perceived stress increase with increasing age after age 65? A population-based study.

    Science.gov (United States)

    Osmanovic-Thunström, Almira; Mossello, Enrico; Åkerstedt, Torbjörn; Fratiglioni, Laura; Wang, Hui-Xin

    2015-09-01

    psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Increased oxidative stress in preschool children exposed to passive smoking.

    Science.gov (United States)

    Yıldırım, Faruk; Sermetow, Kabil; Aycicek, Ali; Kocyigit, Abdurrahim; Erel, Ozcan

    2011-01-01

    To study the effect of passive cigarette smoking on plasma oxidative and antioxidative status in passive smoking preschool children and to compare them with controls. Thirty-four passive smoking (five to 50 cigarettes per day) preschool children (study group) and 32 controls who had never been exposed to cigarette smoke were randomly chosen from children aged from 4 to 6 years. Urinary cotinine and plasma indicators of oxidative and antioxidative status, i.e., total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI), were determined. Mean environmental cigarette consumption was 22±13 cigarettes per day in passive smoking children. Mean urinary cotinine levels were 77.6±41.4 ng/mL and 11.9±2.3 ng/mL in the study and control groups, respectively (p < 0.001). Mean plasma TAC levels were 0.95±0.13 mmol Trolox equivalent/L and 1.01±0.09 mmol Trolox equivalent/L, respectively (p = 0.039). Mean plasma TOS levels were 28.6±7.9 µmol H2O2 equivalent/L and 18.5±6.3 µmol H2O2 equivalent/L, respectively (p < 0.001). Mean OSI levels were 3.08±0.98 arbitrary units and 1.84±0.64 arbitrary units, respectively (p < 0.001). A small amount of cigarette smoke (five to 10 cigarettes per day) causes considerable oxidative stress. There were significant correlations between number of cigarettes consumed and oxidant status and OSI levels. Passive smoke is a potent oxidant in preschool children. Its deleterious effects are not limited just to heavy passive smoking, but also occur with exposure to small amounts of smoke.

  4. Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marion Ortner

    2016-09-01

    Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

  5. Thermomechanical processing of 5083 aluminum to increase strength without increasing susceptibility to stress corrosion cracking

    International Nuclear Information System (INIS)

    Edstrom, C.M.; Blakeslee, J.J.

    1980-01-01

    5083 aluminium with 25% cold work must be processed above 215 0 C or below 70 0 C to avoid forming continuous precipitate in the grain boundaries which makes the material susceptible to stress corrosion cracking. Time at temperature above 215 0 C should be held to minimum (less than 30 min) to retain some strength from the 25% cold work

  6. Heightened amygdala responsiveness in s-carriers of 5-HTTLPR genetic polymorphism reflects enhanced cortical rather than subcortical inputs: An MEG study.

    Science.gov (United States)

    Luo, Qian; Holroyd, Tom; Mitchell, Derek; Yu, Henry; Cheng, Xi; Hodgkinson, Colin; Chen, Gang; McCaffrey, Daniel; Goldman, David; Blair, R James

    2017-09-01

    Short allele carriers (S-carriers) of the serotonin transporter gene (5-HTTLPR) show an elevated amygdala response to emotional stimuli relative to long allele carriers (LL-homozygous). However, whether this reflects increased responsiveness of the amygdala generally or interactions between the amygdala and the specific input systems remains unknown. It is argued that the amygdala receives input via a quick subcortical and a slower cortical pathway. If the elevated amygdala response in S-carriers reflects generally increased amygdala responding, then group differences in amygdala should be seen across the amygdala response time course. However, if the difference is a secondary consequence of enhanced amygdala-cortical interactions, then group differences might only be present later in the amygdala response. Using magnetoencephalography (MEG), we found an enhanced amygdala response to fearful expressions starting 40-50 ms poststimulus. However, group differences in the amygdala were only seen 190-200 ms poststimulus, preceded by increased superior temporal sulcus (STS) responses in S-carriers from 130 to 140 ms poststimulus. An enhanced amygdala response to angry expressions started 260-270 ms poststimulus with group differences in the amygdala starting at 160-170 ms poststimulus onset, preceded by increased STS responses in S-carriers from 150 to 160 ms poststimulus. These suggest that enhanced amygdala responses in S-carriers might reflect enhanced STS-amygdala connectivity in S-carriers. Hum Brain Mapp 38:4313-4321, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Pre-cold stress increases acid stress resistance and induces amino ...

    African Journals Online (AJOL)

    pre-adapted to cold stress revealed induction of amino acid homeostasis and energy ... substrate, thereby reducing yeast and mould ..... spontaneous mutation of llmg_1816 (gdpp) induced by .... species to UV-B-induced damage in bacteria. J.

  8. Involvement of the amygdala in memory storage: Interaction with other brain systems

    OpenAIRE

    McGaugh, James L.; Cahill, Larry; Roozendaal, Benno

    1996-01-01

    There is extensive evidence that the amygdala is involved in affectively influenced memory. The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions. Several lines of evidence support this view. First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving ...

  9. Altered Amygdala Resting-State Functional Connectivity and Hemispheric Asymmetry in Patients With Social Anxiety Disorder

    Directory of Open Access Journals (Sweden)

    Ye-Ha Jung

    2018-04-01

    Full Text Available Background: The amygdala plays a key role in emotional hyperreactivity in response to social threat in patients with social anxiety disorder (SAD. We investigated resting-state functional connectivity (rs-FCN of the left and right amygdala with various brain regions and functional lateralization in patients with SAD.Methods: A total of 36 patients with SAD and 42 matched healthy controls underwent functional magnetic resonance imaging (fMRI at rest. Using the left and right amygdala as seed regions, we compared the strength of the rs-FCN in the patient and control groups. Furthermore, we investigated group differences in the hemispheric asymmetry of the functional connectivity maps of the left and right amygdala.Results: Compared with healthy controls, the rs-FCN between the left amygdala and the dorsolateral prefrontal cortex was reduced in patients with SAD, whereas left amygdala connectivity with the fusiform gyrus, anterior insula, supramarginal gyrus, and precuneus was increased or positively deflected in the patient group. Additionally, the strength rs-FCN between the left amygdala and anterior insula was positively associated with the severity of the fear of negative evaluation in patients with SAD (r = 0.338, p = 0.044. The rs-FCN between the right amygdala and medial frontal gyrus was decreased in patients with SAD compared with healthy controls, whereas connectivity with the parahippocampal gyrus was greater in the patient group than in the control group. The hemispheric asymmetry patterns in the anterior insula, intraparietal sulcus (IPS, and inferior frontal gyrus of the patient group were opposite those of the control group, and functional lateralization of the connectivity between the amygdala and the IPS was associated with the severity of social anxiety symptoms (r = 0.365, p = 0.037.Conclusion: Our findings suggest that in addition to impaired fronto-amygdala communication, the functional lateralization of amygdala function

  10. White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

    Science.gov (United States)

    Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

    2012-01-16

    Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Prenatal stress may increase vulnerability to life events comparison with the effects of prenatal dexamethasone

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Kjaer, Sanna L

    2005-01-01

    naïve at the time of ASR testing, whereas the other had been through blood sampling for assessment of the hormonal stress response to restraint, 3 months previously. Both prenatal CMS and dexamethasone increased ASR in the offspring compared to controls, but only in prenatally stressed offspring......Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...... of the acoustic startle response. Further, a single aversive life event showed capable of changing the reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this event. This suggests that circumstances dating back to the very...

  12. Increase of resistance to cracking on stress relieving of hardened steel

    International Nuclear Information System (INIS)

    Velichko, V.V.; Zabil'skij, V.V.; Mikheev, G.M.

    1995-01-01

    Regularities of increase of resistance to cracking during stress relieving of hardened low-alloyed steels were studied, using complex of methods. Effect of carbon, stress concentrator radius, duration and temperature of stress relieving was studies in particular. Results of investigating kinetics of change of physicomechanical properties, hydrogen desorption from hardened specimens showed, that increase of resistance to cracking was caused by desorption from grain boundaries of diffusion-mobile hydrogen, formed during hardening. 18 refs., 8 figs

  13. The amygdala and ventromedial prefrontal cortex in morality and psychopathy.

    Science.gov (United States)

    Blair, R J R

    2007-09-01

    Recent work has implicated the amygdala and ventromedial prefrontal cortex in morality and, when dysfunctional, psychopathy. This model proposes that the amygdala, through stimulus-reinforcement learning, enables the association of actions that harm others with the aversive reinforcement of the victims' distress. Consequent information on reinforcement expectancy, fed forward to the ventromedial prefrontal cortex, can guide the healthy individual away from moral transgressions. In psychopathy, dysfunction in these structures means that care-based moral reasoning is compromised and the risk that antisocial behavior is used instrumentally to achieve goals is increased.

  14. 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

  15. Dispositional Mindfulness Co-Varies with Smaller Amygdala and Caudate Volumes in Community Adults

    Science.gov (United States)

    Taren, Adrienne A.; Creswell, J. David; Gianaros, Peter J.

    2013-01-01

    Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions) may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala. In the present study, a self-report measure of dispositional mindfulness and structural MRI images were obtained from 155 healthy community adults. Volumetric analyses showed that higher dispositional mindfulness is associated with decreased grey matter volume in the right amygdala, and exploratory analyses revealed that higher dispositional mindfulness is also associated with decreased grey matter volume in the left caudate. Moreover, secondary analyses indicate that these amygdala and caudate volume associations persist after controlling for relevant demographic and individual difference factors (i.e., age, total grey matter volume, neuroticism, depression). Such volumetric differences may help explain why mindful individuals have reduced stress reactivity, and suggest new candidate structural neurobiological pathways linking mindfulness with mental and physical health outcomes. PMID:23717632

  16. Dispositional mindfulness co-varies with smaller amygdala and caudate volumes in community adults.

    Directory of Open Access Journals (Sweden)

    Adrienne A Taren

    Full Text Available Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala. In the present study, a self-report measure of dispositional mindfulness and structural MRI images were obtained from 155 healthy community adults. Volumetric analyses showed that higher dispositional mindfulness is associated with decreased grey matter volume in the right amygdala, and exploratory analyses revealed that higher dispositional mindfulness is also associated with decreased grey matter volume in the left caudate. Moreover, secondary analyses indicate that these amygdala and caudate volume associations persist after controlling for relevant demographic and individual difference factors (i.e., age, total grey matter volume, neuroticism, depression. Such volumetric differences may help explain why mindful individuals have reduced stress reactivity, and suggest new candidate structural neurobiological pathways linking mindfulness with mental and physical health outcomes.

  17. Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination.

    Science.gov (United States)

    Grimm, O; Kraehenmann, R; Preller, K H; Seifritz, E; Vollenweider, F X

    2018-04-24

    Recent studies suggest that the antidepressant effects of the psychedelic 5-HT2A receptor agonist psilocybin are mediated through its modulatory properties on prefrontal and limbic brain regions including the amygdala. To further investigate the effects of psilocybin on emotion processing networks, we studied for the first-time psilocybin's acute effects on amygdala seed-to-voxel connectivity in an event-related face discrimination task in 18 healthy volunteers who received psilocybin and placebo in a double-blind balanced cross-over design. The amygdala has been implicated as a salience detector especially involved in the immediate response to emotional face content. We used beta-series amygdala seed-to-voxel connectivity during an emotional face discrimination task to elucidate the connectivity pattern of the amygdala over the entire brain. When we compared psilocybin to placebo, an increase in reaction time for all three categories of affective stimuli was found. Psilocybin decreased the connectivity between amygdala and the striatum during angry face discrimination. During happy face discrimination, the connectivity between the amygdala and the frontal pole was decreased. No effect was seen during discrimination of fearful faces. Thus, we show psilocybin's effect as a modulator of major connectivity hubs of the amygdala. Psilocybin decreases the connectivity between important nodes linked to emotion processing like the frontal pole or the striatum. Future studies are needed to clarify whether connectivity changes predict therapeutic effects in psychiatric patients. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  18. Altered Amygdala Resting-State Functional Connectivity in Maintenance Hemodialysis End-Stage Renal Disease Patients with Depressive Mood.

    Science.gov (United States)

    Chen, Hui Juan; Wang, Yun Fei; Qi, Rongfeng; Schoepf, U Joseph; Varga-Szemes, Akos; Ball, B Devon; Zhang, Zhe; Kong, Xiang; Wen, Jiqiu; Li, Xue; Lu, Guang Ming; Zhang, Long Jiang

    2017-04-01

    The purpose of this study was to investigate patterns in the amygdala-based emotional processing circuit of hemodialysis patients using resting-state functional MR imaging (rs-fMRI). Fifty hemodialysis patients (25 with depressed mood and 25 without depressed mood) and 26 healthy controls were included. All subjects underwent neuropsychological tests and rs-fMRI, and patients also underwent laboratory tests. Functional connectivity of the bilateral amygdala was compared among the three groups. The relationship between functional connectivity and clinical markers was investigated. Depressed patients showed increased positive functional connectivity of the left amygdala with the left superior temporal gyrus and right parahippocampal gyrus (PHG) but decreased amygdala functional connectivity with the left precuneus, angular gyrus, posterior cingulate cortex (PCC), and left inferior parietal lobule compared with non-depressed patients (P amygdala with bilateral supplementary motor areas and PHG but decreased amygdala functional connectivity with the right superior frontal gyrus, superior parietal lobule, bilateral precuneus, and PCC (P amygdala (P amygdala-prefrontal-PCC-limbic circuits was impaired in depressive hemodialysis patients, with a gradual decrease in ACC between controls, non-depressed, and depressed patients for the right amygdala. This indicates that ACC plays a role in amygdala-based emotional regulatory circuits in these patients.

  19. The human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity

    Science.gov (United States)

    Wang, Shuo; Yu, Rongjun; Tyszka, J. Michael; Zhen, Shanshan; Kovach, Christopher; Sun, Sai; Huang, Yi; Hurlemann, Rene; Ross, Ian B.; Chung, Jeffrey M.; Mamelak, Adam N.; Adolphs, Ralph; Rutishauser, Ueli

    2017-01-01

    The human amygdala is a key structure for processing emotional facial expressions, but it remains unclear what aspects of emotion are processed. We investigated this question with three different approaches: behavioural analysis of 3 amygdala lesion patients, neuroimaging of 19 healthy adults, and single-neuron recordings in 9 neurosurgical patients. The lesion patients showed a shift in behavioural sensitivity to fear, and amygdala BOLD responses were modulated by both fear and emotion ambiguity (the uncertainty that a facial expression is categorized as fearful or happy). We found two populations of neurons, one whose response correlated with increasing degree of fear, or happiness, and a second whose response primarily decreased as a linear function of emotion ambiguity. Together, our results indicate that the human amygdala processes both the degree of emotion in facial expressions and the categorical ambiguity of the emotion shown and that these two aspects of amygdala processing can be most clearly distinguished at the level of single neurons. PMID:28429707

  20. Increasing stress on disaster risk finance due to large floods

    Science.gov (United States)

    Jongman, Brenden; Hochrainer-Stigler, Stefan; Feyen, Luc; Aerts, Jeroen; Mechler, Reinhard; Botzen, Wouter; Bouwer, Laurens; Pflug, Georg; Rojas, Rodrigo; Ward, Philip

    2014-05-01

    Recent major flood disasters have shown that single extreme events can affect multiple countries simultaneously, which puts high pressure on trans-national risk reduction and risk transfer mechanisms. To date, little is known about such flood hazard interdependencies across regions, and the corresponding joint risks at regional to continental scales. Reliable information on correlated loss probabilities is crucial for developing robust insurance schemes and public adaptation funds, and for enhancing our understanding of climate change impacts. Here we show that extreme discharges are strongly correlated across European river basins and that these correlations can, or should, be used in national to continental scale risk assessment. We present probabilistic trends in continental flood risk, and demonstrate that currently observed extreme flood losses could more than double in frequency by 2050 under future climate change and socioeconomic development. The results demonstrate that accounting for tail dependencies leads to higher estimates of extreme losses than estimates based on the traditional assumption of independence between basins. We suggest that risk management for these increasing losses is largely feasible, and we demonstrate that risk can be shared by expanding risk transfer financing, reduced by investing in flood protection, or absorbed by enhanced solidarity between countries. We conclude that these measures have vastly different efficiency, equity and acceptability implications, which need to be taken into account in broader consultation, for which our analysis provides a basis.

  1. Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice.

    Science.gov (United States)

    Brzozowska, Natalia I; Smith, Kristie L; Zhou, Cilla; Waters, Peter M; Cavalcante, Ligia Menezes; Abelev, Sarah V; Kuligowski, Michael; Clarke, David J; Todd, Stephanie M; Arnold, Jonathon C

    2017-10-01

    P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier and regulates the brain uptake of various xenobiotics and endogenous mediators including glucocorticoid hormones which are critically important to the stress response. Moreover, P-gp is expressed on microglia, the brain's immune cells, which are activated by stressors and have an emerging role in psychiatric disorders. We therefore hypothesised that germline P-gp deletion in mice might alter the behavioral and microglial response to stressors. Female P-gp knockout mice displayed an unusual, frantic anxiety response to intraperitoneal injection stress in the light-dark test. They also tended to display reduced conditioned fear responses compared to wild-type (WT) mice in a paradigm where a single electric foot-shock stressor was paired to a context. Foot-shock stress reduced social interaction and decreased microglia cell density in the amygdala which was not varied by P-gp genotype. Independently of stressor exposure, female P-gp deficient mice displayed increased depression-like behavior, idiosyncratic darting behavior, age-related social withdrawal and hyperactivity, facilitated sensorimotor gating and altered startle reactivity. In addition, P-gp deletion increased microglia cell density in the CA3 region of the hippocampus, and the microglial cells exhibited a reactive, hypo-ramified morphology. Further, female P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the hippocampus. In conclusion, this research shows that germline P-gp deletion affected various behaviors of relevance to psychiatric conditions, and that altered microglial cell activity and enhanced GR expression in the hippocampus may play a role in mediating these behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior: study 3--the effects on amygdala efferent physiology of block of NMDA receptors prior to injection of FG-7142 and its relationship to behavioral change.

    Science.gov (United States)

    Adamec, R E

    1998-01-01

    The findings of this study support the hypothesis that N-methyl-D-aspartate (NMDA) receptors mediate the initiation of long-term potentiation (LTP) and behavioral changes induced by the anxiogenic beta-carboline, FG-7142. Unlike previous work, this study examined the effects of FG-7142 on LTP of amygdala efferents in both hemispheres. 7-amino-phosphono-heptanoic acid (AP7), a competitive NMDA receptor blocker, given prior to administration of FG-7142, prevented LTP in amygdala efferent transmission to the medial hypothalamus and periacqueductal gray (PAG). When given FG-7142 alone, cats showed lasting behavioral changes accompanied by LTP in all pathways studied. Duration of LTP, and its relationship to behavioral change, depended on the pathway and the hemisphere of the pathway. Correlation and covariance analyses indicate that LTP in the left amygdalo-ventromedial hypothalamic pathway mediates initiation, but not maintenance, of increased defensiveness. This finding replicates previous work. A new finding is that increased local excitability in the right basal amygdala (reduced threshold for evoked response), and LTP in the right amygdalo-PAG pathway, may be important for maintenance of increases in defensive behavior. Furthermore, the effects of flumazenil, a benzodiazepine receptor antagonist, on behavior and physiology single out the importance of right amygdalo-PAG LTP as a critical mediator of increased defensiveness. Flumazenil reversed the increase in defensiveness produced by FG-7142 in a drug-dependent manner as described in Adamec (1998a). Moreover, flumazenil reversed LTP only in the right amygdalo-PAG pathway. The findings of the present study suggest that response to FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety, especially in view of the recent data in humans implicating right hemispheric function in persisting negative affective states.

  3. Stressful task increases drive for thinness and bulimia: a laboratory study.

    Directory of Open Access Journals (Sweden)

    Sandra eSassaroli

    2015-05-01

    Full Text Available The scientific literature has suggested that stress undergirds the development of eating disorders (ED. Therefore, this study explored whether laboratory induced stress increases self-reported drive for thinness and bulimic symptoms measured via self-report. The relationship between control, perfectionism, stress, and cognition related to ED was examined using correlational methodology. 86 participants completed an experimental task using a personal computer. All individuals completed a battery of tests before and after the stressful task. Analyses showed a significant statistical increase in average scores on the drive for thinness and bulimia measured before and after a stressful task, and path analysis revealed two different cognitive models for the mechanism leading to drive for thinness and bulimia. These findings suggest that stress is an important factor in the development of the drive for thinness and bulimia.

  4. Overprotective social support leads to increased cardiovascular and subjective stress reactivity.

    Science.gov (United States)

    Zniva, Richard; Pauli, Paul; Schulz, Stefan M

    2017-02-01

    Self-determination theory suggests that autonomy-enhancing social support helps individuals to perceive stressors as challenging rather than stressing. Overprotective support may reduce stress in the short-run but undermines autonomy, thus hampering stress-coping in the long run, particularly when social support is terminated. Heartrate, blood-pressure and ratings were examined in N=44 undergraduate students receiving autonomy support (calculation steps) or overprotection (solutions) from a close friend or no support for solving arithmetic tasks as well as during a subsequent stress-challenge (solving arithmetic tasks alone). Overprotection resulted in increased heartrate, diastolic blood-pressure, stress ratings, and decreased subjective control during stress-challenge. Autonomy support did not lead to unfavorable stress responding. The current findings are in line with assumptions derived from self-determination theory and indicate that autonomy support can help to prevent stress. Overprotection does not buffer stress and is associated with increased stress when discontinued. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Respiratory sinus arrhythmia during worry forecasts stress-related increases in psychological distress.

    Science.gov (United States)

    Gouin, Jean-Philippe; Deschênes, Sonya S; Dugas, Michel J

    2014-09-01

    Respiratory sinus arrhythmia (RSA) has been conceptualized as an index of emotion regulation abilities. Although resting RSA has been associated with both concurrent and prospective affective responses to stress, the impact of RSA reactivity on emotional responses to stress is inconsistent across studies. The type of emotional stimuli used to elicit these phasic RSA responses may influence the adaptive value of RSA reactivity. We propose that RSA reactivity to a personally relevant worry-based stressor might forecast future affective responses to stress. To evaluate whether resting RSA and RSA reactivity to worry inductions predict stress-related increases in psychological distress, an academic stress model was used to prospectively examine changes in psychological distress from the well-defined low- and high-stress periods. During the low-stress period, 76 participants completed self-report mood measures and had their RSA assessed during a resting baseline, free worry period and worry catastrophizing interview. Participants completed another mood assessment during the high-stress period. Results indicated that baseline psychological distress predicted larger decreases in RSA during the worry inductions. Lower resting RSA and greater RSA suppression to the worry inductions at baseline prospectively predicted larger increases in psychological distress from the low- to high-stress period, even after accounting for the impact of baseline distress on RSA. These results provide further evidence that RSA may represent a unique index of emotion regulation abilities in times of stress.

  6. Stressful task increases drive for thinness and bulimia: a laboratory study

    OpenAIRE

    Sassaroli, Sandra; Fiore, Francesca; Mezzaluna, Clarice; Ruggiero, Giovanni Maria

    2015-01-01

    The scientific literature has suggested that stress undergirds the development of eating disorders (ED). Therefore, this study explored whether laboratory induced stress increases self-reported drive for thinness and bulimic symptoms measured via self-report. The relationship between control, perfectionism, stress, and cognition related to ED was examined using correlational methodology. Eighty-six participants completed an experimental task using a personal computer (PC). All individuals com...

  7. Discrimination of amygdala response predicts future separation anxiety in youth with early deprivation.

    Science.gov (United States)

    Green, Shulamite A; Goff, Bonnie; Gee, Dylan G; Gabard-Durnam, Laurel; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Louie, Jennifer; Tottenham, Nim

    2016-10-01

    Significant disruption in caregiving is associated with increased internalizing symptoms, most notably heightened separation anxiety symptoms during childhood. It is also associated with altered functional development of the amygdala, a neurobiological correlate of anxious behavior. However, much less is known about how functional alterations of amygdala predict individual differences in anxiety. Here, we probed amygdala function following institutional caregiving using very subtle social-affective stimuli (trustworthy and untrustworthy faces), which typically result in large differences in amygdala signal, and change in separation anxiety behaviors over a 2-year period. We hypothesized that the degree of differentiation of amygdala signal to trustworthy versus untrustworthy face stimuli would predict separation anxiety symptoms. Seventy-four youths mean (SD) age = 9.7 years (2.64) with and without previous institutional care, who were all living in families at the time of testing, participated in an fMRI task designed to examine differential amygdala response to trustworthy versus untrustworthy faces. Parents reported on their children's separation anxiety symptoms at the time of scan and again 2 years later. Previous institutional care was associated with diminished amygdala signal differences and behavioral differences to the contrast of untrustworthy and trustworthy faces. Diminished differentiation of these stimuli types predicted more severe separation anxiety symptoms 2 years later. Older age at adoption was associated with diminished differentiation of amygdala responses. A history of institutional care is associated with reduced differential amygdala responses to social-affective cues of trustworthiness that are typically exhibited by comparison samples. Individual differences in the degree of amygdala differential responding to these cues predict the severity of separation anxiety symptoms over a 2-year period. These findings provide a biological

  8. Increased risk taking in relation to chronic stress in young adults

    Directory of Open Access Journals (Sweden)

    Smarandita eCeccato

    2016-01-01

    Full Text Available Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured learning-independent risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self-reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS. We additionally collected hair samples in a subsample of volunteers, in order to quantify chronic cortisol exposure. We discovered a significant, positive correlation between self-reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations.

  9. Prefrontal control of the amygdala during real-time fMRI neurofeedback training of emotion regulation.

    Directory of Open Access Journals (Sweden)

    Vadim Zotev

    Full Text Available We observed in a previous study (PLoS ONE 6:e24522 that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC, bilateral dorsomedial prefrontal cortex (DMPFC, bilateral superior frontal gyrus (SFG, and right medial frontopolar cortex (MFPC. Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a significant enhancement in the time-lagged effect of the left rACC on the LA, potentially consistent with the ipsilateral distribution of the monosynaptic projections between these regions. The training is also accompanied by significant increases in the instantaneous (contemporaneous effects of the left rACC on four other regions - the bilateral DMPFC, the right MFPC, and the left SFG. The instantaneous effects of the LA on the bilateral DMPFC are also significantly enhanced. Our results are consistent with a broad literature supporting the role of the rACC in emotion processing and regulation. Our exploratory analysis provides, for the first time, insights into the causal relationships within the network of regions engaged during the rtfMRI-nf procedure targeting the amygdala. It suggests that the rACC may constitute a promising target for rtfMRI-nf training along with the amygdala in patients with affective disorders, particularly posttraumatic stress

  10. Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression.

    Science.gov (United States)

    Bassi, Sabrina; Seney, Marianne L; Argibay, Pablo; Sibille, Etienne

    2015-04-01

    The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N = 16 pairs; males: N = 12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N = 6 pairs; males: N = 6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p < 0.0001), but not males, and of UCMS-exposed mice (males and females; p = 0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p = 0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p < 0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

    Science.gov (United States)

    Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

    2011-01-01

    Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

  12. Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

    Directory of Open Access Journals (Sweden)

    Ana Montero-Pedrazuela

    Full Text Available Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

  13. Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

    Science.gov (United States)

    Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

    2011-01-01

    Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment. PMID:22039511

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

    Science.gov (United States)

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

    2017-05-01

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

  15. Emotional memory consolidation under lower versus higher stress conditions

    Directory of Open Access Journals (Sweden)

    Inna eKogan

    2010-12-01

    Full Text Available An exposure to stress can enhance memory for emotionally arousing experiences. The phenomenon is suggested to be amygdala-dependent and in accordance with that view the amygdala was found to modulate mnemonic processes in other brain regions. Previously, we illustrated increased amygdala activation and reduced activation of CA1 following spatial learning under high versus low emotionality conditions. When spatial learning was followed by reversal training interference, impaired retention was detected only under high emotionality conditions. Here we further evaluate the potential implications of the difference in the level of amygdala activation on the quality of the memory formed under these stress conditions. We attempted to affect spatial memory consolidation under low or high stress conditions by either introducing a foot shock interference following massed training in the water maze; by manipulating the threshold for acquisition employing either brief (3 trials or full (12 trials training sessions; or by employing a spaced training (over three days rather than massed training protocol. The current findings reveal that under heightened emotionality, the process of consolidation seems to become less effective and more vulnerable to interference; however, when memory consolidation is not interrupted, retention is improved. These differential effects might underlie the complex interactions of stress, and, particularly, of traumatic stress with memory formation processes.

  16. Amygdala functional disconnection with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood.

    Science.gov (United States)

    Chen, Yu-Chen; Bo, Fan; Xia, Wenqing; Liu, Shenghua; Wang, Peng; Su, Wen; Xu, Jin-Jing; Xiong, Zhenyu; Yin, Xindao

    2017-10-03

    Chronic tinnitus is often accompanied with depressive symptom, which may arise from aberrant functional coupling between the amygdala and cerebral cortex. To explore this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to investigate the disrupted amygdala-cortical functional connectivity (FC) in chronic tinnitus patients with depressive mood. Chronic tinnitus patients with depressive mood (n=20), without depressive mood (n=20), and well-matched healthy controls (n=23) underwent resting-state fMRI scanning. Amygdala-cortical FC was characterized using a seed-based whole-brain correlation method. The bilateral amygdala FC was compared among the three groups. Compared to non-depressed patients, depressive tinnitus patients showed decreased amygdala FC with the prefrontal cortex and anterior cingulate cortex as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. Relative to healthy controls, depressive tinnitus patients revealed decreased amygdala FC with the superior and middle temporal gyrus, anterior and posterior cingulate cortex, and prefrontal cortex, as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. The current study identified for the first time abnormal resting-state amygdala-cortical FC with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood, which will provide novel insight into the underlying neuropathological mechanisms of tinnitus-induced depressive disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

    Science.gov (United States)

    RATIONALE: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and gluoose intolerance that are assoc...

  18. Oral contraceptive therapy increases oxidative stress in pre-menopausal women

    Directory of Open Access Journals (Sweden)

    Jui Tung Chen

    2012-01-01

    Conclusions: The use of OCT may increase oxidative stress levels, independent of traditional cardiovascular risk factors, in pre-menopausal women, providing new insights to the primary prevention of vascular complications in these subjects.

  19. Abnormal amygdala connectivity in patients with primary insomnia: Evidence from resting state fMRI

    International Nuclear Information System (INIS)

    Huang Zhaoyang; Liang Peipeng; Jia Xiuqin; Zhan Shuqin; Li Ning; Ding Yan; Lu Jie; Wang Yuping; Li Kuncheng

    2012-01-01

    Background: Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Methods: Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. Results: We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). Conclusions: The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients.

  20. Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI.

    Science.gov (United States)

    Huang, Zhaoyang; Liang, Peipeng; Jia, Xiuqin; Zhan, Shuqin; Li, Ning; Ding, Yan; Lu, Jie; Wang, Yuping; Li, Kuncheng

    2012-06-01

    Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Functional Connectivity of the Amygdala Is Disrupted in Preschool-Aged Children With Autism Spectrum Disorder.

    Science.gov (United States)

    Shen, Mark D; Li, Deana D; Keown, Christopher L; Lee, Aaron; Johnson, Ryan T; Angkustsiri, Kathleen; Rogers, Sally J; Müller, Ralph-Axel; Amaral, David G; Nordahl, Christine Wu

    2016-09-01

    The objective of this study was to determine whether functional connectivity of the amygdala is altered in preschool-age children with autism spectrum disorder (ASD) and to assess the clinical relevance of observed alterations in amygdala connectivity. A resting-state functional connectivity magnetic resonance imaging study of the amygdala (and a parallel study of primary visual cortex) was conducted in 72 boys (mean age 3.5 years; n = 43 with ASD; n = 29 age-matched controls). The ASD group showed significantly weaker connectivity between the amygdala and several brain regions involved in social communication and repetitive behaviors, including bilateral medial prefrontal cortex, temporal lobes, and striatum (p amygdala and frontal and temporal lobes was significantly correlated with increased autism severity in the ASD group (p amygdala and regions of the brain important for social communication and language, which might be clinically relevant because weaker connectivity was associated with increased autism severity. Moreover, although amygdala connectivity was associated with behavioral domains that are diagnostic of ASD, altered connectivity of primary visual cortex was related to sensory hypersensitivity. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Prior stress exposure increases pain behaviors in a rat model of full thickness thermal injury.

    Science.gov (United States)

    Nyland, Jennifer E; McLean, Samuel A; Averitt, Dayna L

    2015-12-01

    Thermal burns among individuals working in highly stressful environments, such as firefighters and military Service Members, are common. Evidence suggests that pre-injury stress may exaggerate pain following thermal injury; however current animal models of burn have not evaluated the potential influence of pre-burn stress. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to 20 min of inescapable swim stress or sham stress once per day for three days. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn and (2) accelerated the onset of thermal hyperalgesia and mechanical allodynia after subsequent burn. This stress-induced exacerbation of pain sensitivity was reversed by pretreatment and concurrent treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn may lead to improved pain treatments for burn survivors. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  3. Transgenic tobacco plants constitutively expressing peanut BTF3 exhibit increased growth and tolerance to abiotic stresses.

    Science.gov (United States)

    Pruthvi, V; Rama, N; Parvathi, M S; Nataraja, K N

    2017-05-01

    Abiotic stresses limit crop growth and productivity worldwide. Cellular tolerance, an important abiotic stress adaptive trait, involves coordinated activities of multiple proteins linked to signalling cascades, transcriptional regulation and other diverse processes. Basal transcriptional machinery is considered to be critical for maintaining transcription under stressful conditions. From this context, discovery of novel basal transcription regulators from stress adapted crops like peanut would be useful for improving tolerance of sensitive plant types. In this study, we prospected a basal transcription factor, BTF3 from peanut (Arachis hypogaea L) and studied its relevance in stress acclimation by over expression in tobacco. AhBTF3 was induced under PEG-, NaCl-, and methyl viologen-induced stresses in peanut. The constitutive expression of AhBTF3 in tobacco increased plant growth under non stress condition. The transgenic plants exhibited superior phenotype compared to wild type under mannitol- and NaCl-induced stresses at seedling level. The enhanced cellular tolerance of transgenic plants was evidenced by higher cell membrane stability, reactive oxygen species (ROS) scavenging activity, seedling survival and vigour than wild type. The transgenic lines showed better in vitro regeneration capacity on growth media supplemented with NaCl than wild type. Superior phenotype of transgenic plants under osmotic and salinity stresses seems to be due to constitutive activation of genes of multiple pathways linked to growth and stress adaptation. The study demonstrated that AhBTF3 is a positive regulator of growth and stress acclimation and hence can be considered as a potential candidate gene for crop improvement towards stress adaptation. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

  4. The amygdala and decision-making.

    Science.gov (United States)

    Gupta, Rupa; Koscik, Timothy R; Bechara, Antoine; Tranel, Daniel

    2011-03-01

    Decision-making is a complex process that requires the orchestration of multiple neural systems. For example, decision-making is believed to involve areas of the brain involved in emotion (e.g., amygdala, ventromedial prefrontal cortex) and memory (e.g., hippocampus, dorsolateral prefrontal cortex). In this article, we will present findings related to the amygdala's role in decision-making, and differentiate the contributions of the amygdala from those of other structurally and functionally connected neural regions. Decades of research have shown that the amygdala is involved in associating a stimulus with its emotional value. This tradition has been extended in newer work, which has shown that the amygdala is especially important for decision-making, by triggering autonomic responses to emotional stimuli, including monetary reward and punishment. Patients with amygdala damage lack these autonomic responses to reward and punishment, and consequently, cannot utilize "somatic marker" type cues to guide future decision-making. Studies using laboratory decision-making tests have found deficient decision-making in patients with bilateral amygdala damage, which resembles their real-world difficulties with decision-making. Additionally, we have found evidence for an interaction between sex and laterality of amygdala functioning, such that unilateral damage to the right amygdala results in greater deficits in decision-making and social behavior in men, while left amygdala damage seems to be more detrimental for women. We have posited that the amygdala is part of an "impulsive," habit type system that triggers emotional responses to immediate outcomes. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Endoplasmic reticulum stress is increased in adipose tissue of women with gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Stella Liong

    Full Text Available Maternal obesity and gestational diabetes mellitus (GDM are two increasingly common and important obstetric complications that are associated with severe long-term health risks to mothers and babies. IL-1β, which is increased in obese and GDM pregnancies, plays an important role in the pathophysiology of these two pregnancy complications. In non-pregnant tissues, endoplasmic (ER stress is increased in diabetes and can induce IL-1β via inflammasome activation. The aim of this study was to determine whether ER stress is increased in omental adipose tissue of women with GDM, and if ER stress can also upregulate inflammasome-dependent secretion of IL-1β. ER stress markers IRE1α, GRP78 and XBP-1s were significantly increased in adipose tissue of obese compared to lean pregnant women. ER stress was also increased in adipose tissue of women with GDM compared to BMI-matched normal glucose tolerant (NGT women. Thapsigargin, an ER stress activator, induced upregulated secretion of mature IL-1α and IL-1β in human omental adipose tissue explants primed with bacterial endotoxin LPS, the viral dsRNA analogue poly(I:C or the pro-inflammatory cytokine TNF-α. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1α and IL-1β secretion, whereas inhibition of pannexin-1 with carbenoxolone suppressed IL-1β secretion only. Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1α and IL-1β secretion in infection and cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER stress to activate the inflammasome in pregnant adipose tissue. Therefore, increased ER stress may contribute towards the pathophysiology of obesity in pregnancy and GDM.

  6. Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness

    Directory of Open Access Journals (Sweden)

    Bas C. T. van Bussel

    2017-02-01

    Full Text Available Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care.

  7. 0268 Is perceived stress related to an increase in salivary cortisol

    DEFF Research Database (Denmark)

    Fink, Samuel; Peter Bonde, Jens; Agergaard Vammen, Marianne

    2014-01-01

    OBJECTIVES: Perceived Stress is a suspected cause of many psychological and physical illnesses. However it remains to be discovered what physiological measures are involved. While it is widely known that acute stress leads to an increase in cortisol levels, the findings in prolonged stress research...... have not been consistent. This study explores the association between Perceived Stress and salivary cortisol levels using the largest population ever used in this field. METHOD: 4467 public employees in the PRISME cohort in 2007. 3217 of those did a similar follow up study in 2009. A 4-item Danish...... version of the PSS-scale was used to measure perceived stress and operationalized as the average score. Salivary cortisol samples were taken at 30 min post awakening and at 8 pm. A mean value of cortisol was calculated. In our analysis we applied logarithmic transformation to the concentrations. RESULTS...

  8. When bad stress goes good: increased threat reactivity predicts improved category learning performance.

    Science.gov (United States)

    Ell, Shawn W; Cosley, Brandon; McCoy, Shannon K

    2011-02-01

    The way in which we respond to everyday stressors can have a profound impact on cognitive functioning. Maladaptive stress responses in particular are generally associated with impaired cognitive performance. We argue, however, that the cognitive system mediating task performance is also a critical determinant of the stress-cognition relationship. Consistent with this prediction, we observed that stress reactivity consistent with a maladaptive, threat response differentially predicted performance on two categorization tasks. Increased threat reactivity predicted enhanced performance on an information-integration task (i.e., learning is thought to depend upon a procedural-based memory system), and a (nonsignificant) trend for impaired performance on a rule-based task (i.e., learning is thought to depend upon a hypothesis-testing system). These data suggest that it is critical to consider both variability in the stress response and variability in the cognitive system mediating task performance in order to fully understand the stress-cognition relationship.

  9. Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.

    Directory of Open Access Journals (Sweden)

    Frederique Chaperon

    Full Text Available Links between synaptic plasticity in the lateral amygdala (LA and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA. Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe(6, Leu-NHEt(13, des-Met(14-Bombesin (6-14 did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders.

  10. Lower amygdala volume in men is associated with childhood aggression, early psychopathic traits, and future violence.

    Science.gov (United States)

    Pardini, Dustin A; Raine, Adrian; Erickson, Kirk; Loeber, Rolf

    2014-01-01

    Reduced amygdala volume has been implicated in the development of severe and persistent aggression and the development of psychopathic personality. With longitudinal data, the current study examined whether male subjects with lower amygdala volume have a history of aggression and psychopathic features dating back to childhood and are at increased risk for engaging in future aggression/violence. Participants were selected from a longitudinal study of 503 male subjects initially recruited when they were in the first grade in 1986-1987. At age 26, a subsample of 56 men with varying histories of violence was recruited for a neuroimaging substudy. Automated segmentation was used to index individual differences in amygdala volume. Analyses examined the association between amygdala volume and levels of aggression and psychopathic features of participants measured in childhood and adolescence. Analyses also examined whether amygdala volume was associated with violence and psychopathic traits assessed at a 3-year follow-up. Men with lower amygdala volume exhibited higher levels of aggression and psychopathic features from childhood to adulthood. Lower amygdala volume was also associated with aggression, violence, and psychopathic traits at a 3-year follow-up, even after controlling for earlier levels of these features. All effects remained after accounting for several potential confounds. This represents the first prospective study to demonstrate that men with lower amygdala volume have a longstanding history of aggression and psychopathic features and are at increased risk for committing future violence. Studies should further examine whether specific amygdala abnormalities might be a useful biomarker for severe and persistent aggression. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity.

    Science.gov (United States)

    Lupien, Sonia J; Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France

    2018-04-01

    For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Effects of the medial or basolateral amygdala upon social anxiety and social recognition in mice.

    Science.gov (United States)

    Wang, Yu; Zhao, Shanshan; Liu, Xu; Fu, Qunying

    2014-01-01

    Though social anxiety and social recognition have been studied extensively, the roles of the medial or basolateral amygdala in the control of social anxiety and social recognition remain to be determined. This study investigated the effects of excitotoxic bilateral medial or basolateral amygdala lesions upon social anxiety and social recognition in-mice. Animals at 9 weeks of age were given bilateral medial or basolateral amygdala lesions via infusion of N-methyl- D-aspartate and then were used for behavioral tests: anxiety-related tests (including open-field test, light-dark test, and elevated-plus maze test), social behavior test in a novel environment, social recognition test, and flavor recognition test. Medial or basolateral amygdala-lesioned mice showed lower levels of anxiety and increased social behaviors in a novel environment. Destruction of the medial or basolateral amygdala neurons impaired social recognition but not flavor recognition. The medial or basolateral amygdala is involved in the control of anxiety-related behavior (social anxiety and social behaviors) in mice. Moreover, both the medial and the basolateral amygdala are essential for social recognition but not flavor recognition in mice.

  13. Amygdala hyperactivation during symptom provocation in obsessive–compulsive disorder and its modulation by distraction

    Directory of Open Access Journals (Sweden)

    Daniela Simon

    2014-01-01

    Full Text Available Anxiety disorders have been linked to a hyperactivated cortico-amygdalar circuitry. Recent findings highlight the amygdala's role in mediating elevated anxiety in obsessive–compulsive disorder (OCD. However, modulation of amygdala hyperactivation by attentional distraction – an effective emotion regulation strategy in healthy individuals – has not yet been examined. While undergoing functional magnetic resonance imaging twenty-one unmedicated OCD patients and 21 controls performed an evaluation and a distraction task during symptom provocation with individually tailored OCD-relevant pictures. To test the specificity of responses, additional aversive and neutral stimuli were included. Significant group-by-picture type interactions were observed within fronto–striato–limbic circuits including the amygdala. In these regions patients showed increased BOLD responses during processing of OCD triggers relative to healthy controls. Amygdala hyperactivation was present across OCD symptom dimensions indicating that it represents a common neural correlate. During distraction, we observed dampening of patients' amygdala hyperactivity to OCD-relevant stimuli. Augmented amygdala involvement in patients during symptom provocation, present across OCD symptom dimensions, might constitute a correlate of fear expression in OCD linking it to other anxiety disorders. Attentional distraction seemed to dampen emotional processing of disorder-relevant stimuli via amygdala downregulation. The clinical impact of this strategy to manage anxiety in OCD should be further elucidated.

  14. The interplay of attention and emotion: top-down attention modulates amygdala activation in psychopathy.

    Science.gov (United States)

    Larson, Christine L; Baskin-Sommers, Arielle R; Stout, Daniel M; Balderston, Nicholas L; Curtin, John J; Schultz, Douglas H; Kiehl, Kent A; Newman, Joseph P

    2013-12-01

    Psychopathic behavior has long been attributed to a fundamental deficit in fear that arises from impaired amygdala function. Growing evidence has demonstrated that fear-potentiated startle (FPS) and other psychopathy-related deficits are moderated by focus of attention, but to date, no work on adult psychopathy has examined attentional modulation of the amygdala or concomitant recruitment of relevant attention-related circuitry. Consistent with previous FPS findings, here we report that psychopathy-related differences in amygdala activation appear and disappear as a function of goal-directed attention. Specifically, decreased amygdala activity was observed in psychopathic offenders only when attention was engaged in an alternative goal-relevant task prior to presenting threat-relevant information. Under this condition, psychopaths also exhibited greater activation in selective-attention regions of the lateral prefrontal cortex (LPFC) than did nonpsychopaths, and this increased LPFC activation mediated psychopathy's association with decreased amygdala activation. In contrast, when explicitly attending to threat, amygdala activation did not differ in psychopaths and nonpsychopaths. This pattern of amygdala activation highlights the potential role of LPFC in mediating the failure of psychopathic individuals to process fear and other important information when it is peripheral to the primary focus of goal-directed attention.

  15. MRI Amygdala Volume in Williams Syndrome

    Science.gov (United States)

    Capitao, Liliana; Sampaio, Adriana; Sampaio, Cassandra; Vasconcelos, Cristiana; Fernandez, Montse; Garayzabal, Elena; Shenton, Martha E.; Goncalves, Oscar F.

    2011-01-01

    One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched…

  16. Perceived Workplace Stress Is Associated with an Increased Risk of Prostate Cancer before Age 65.

    Science.gov (United States)

    Blanc-Lapierre, Audrey; Rousseau, Marie-Claude; Parent, Marie-Elise

    2017-01-01

    Evidence is lacking regarding the potential role of chronic psychological stress on cancer incidence. The workplace is reported to be the main source of stress among Canadian men. We examined the association between perceived lifetime workplace stress and prostate cancer (PCa) risk in a large case-control study. Cases were 1,933 men, aged ≤ 75 years, newly diagnosed with PCa in 2005-2009 across hospitals in Montreal, Canada. Concurrently, 1994 population controls frequency-matched on age were randomly selected from the electoral list based on cases' residential districts. Detailed lifestyle and work histories (including perceived stress, from any type of work stressor, for each job held) were collected during in-person interviews. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between work-related stress and PCa risk in multivariate analyses. Over the lifetime, 58% of subjects reported at least one job as stressful. Occupations described as stressful were most often among white-collar workers. Perceived workplace stress duration was associated with a higher risk of PCa (OR = 1.12, 95% CI:1.04-1.20 per 10-year increase) among men younger than 65 years, but not among older men. Associations were similar irrespective of PCa aggressiveness. Frequent or recent screening for PCa, age at first exposure and time since exposure to work-related stress, and socioeconomic and lifestyle factors, had little influence on risk estimates. Findings are in line with an association between reporting prolonged workplace stress and an increase in risk of PCa before age 65.

  17. Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD.

    Science.gov (United States)

    Andero, Raül; Brothers, Shaun P; Jovanovic, Tanja; Chen, Yen T; Salah-Uddin, Hasib; Cameron, Michael; Bannister, Thomas D; Almli, Lynn; Stevens, Jennifer S; Bradley, Bekh; Binder, Elisabeth B; Wahlestedt, Claes; Ressler, Kerry J

    2013-06-05

    The amygdala-dependent molecular mechanisms driving the onset and persistence of posttraumatic stress disorder (PTSD) are poorly understood. Recent observational studies have suggested that opioid analgesia in the aftermath of trauma may decrease the development of PTSD. Using a mouse model of dysregulated fear, we found altered expression within the amygdala of the Oprl1 gene (opioid receptor-like 1), which encodes the amygdala nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic and central amygdala infusion of SR-8993, a new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, a single-nucleotide polymorphism (SNP) within OPRL1 is associated with a self-reported history of childhood trauma and PTSD symptoms (n = 1847) after a traumatic event. This SNP is also associated with physiological startle measures of fear discrimination and magnetic resonance imaging analysis of amygdala-insula functional connectivity. Together, these data suggest that Oprl1 is associated with amygdala function, fear processing, and PTSD symptoms. Further, our data suggest that activation of the Oprl1/NOP receptor may interfere with fear memory consolidation, with implications for prevention of PTSD after a traumatic event.

  18. Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients.

    Science.gov (United States)

    Koch, Saskia Bj; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-05-01

    Post-traumatic stress disorder (PTSD) is a disabling psychiatric disorder. As a substantial part of PTSD patients responds poorly to currently available psychotherapies, pharmacological interventions boosting treatment response are needed. Because of its anxiolytic and pro-social properties, the neuropeptide oxytocin (OT) has been proposed as promising strategy for treatment augmentation in PTSD. As a first step to investigate the therapeutic potential of OT in PTSD, we conducted a double-blind, placebo-controlled, cross-over functional MRI study examining OT administration effects (40 IU) on amygdala reactivity toward emotional faces in unmedicated male and female police officers with (n=37, 21 males) and without (n=40, 20 males) PTSD. Trauma-exposed controls were matched to PTSD patients based on age, sex, years of service and educational level. Under placebo, the expected valence-dependent amygdala reactivity (ie, greater activity toward fearful-angry faces compared with happy-neutral faces) was absent in PTSD patients. OT administration dampened amygdala reactivity toward all emotional faces in male and female PTSD patients, but enhanced amygdala reactivity in healthy male and female trauma-exposed controls, independent of sex and stimulus valence. In PTSD patients, greater anxiety prior to scanning and amygdala reactivity during the placebo session were associated with greater reduction of amygdala reactivity after OT administration. Taken together, our results indicate presumably beneficial neurobiological effects of OT administration in male and female PTSD patients. Future studies should investigate OT administration in clinical settings to fully appreciate its therapeutic potential.

  19. Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study.

    Science.gov (United States)

    Nakayama, Yoko; Masuda, Hiroshi; Shirozu, Hiroshi; Ito, Yosuke; Higashijima, Takefumi; Kitaura, Hiroki; Fujii, Yukihiko; Kakita, Akiyoshi; Fukuda, Masafumi

    2017-09-01

    It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. There was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm 3 ; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10× -4 number of neurons/μm 2 ; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Reward anticipation modulates the effect of stress-related increases in cortisol on episodic memory.

    Science.gov (United States)

    Quent, Jörn A; McCullough, Andrew M; Sazma, Matt; Wolf, Oliver T; Yonelinas, Andrew P

    2018-01-01

    When acute stress is experienced shortly after an event is encoded into memory, this can slow the forgetting of the study event, which is thought to reflect the effect of cortisol on consolidation. In addition, when events are encoded under conditions of high reward they tend to be remembered better than those encoded under non-rewarding conditions, and these effects are thought to reflect the operation of the dopaminergic reward system. Although both modulatory systems are believed to impact the medial temporal lobe regions critical for episodic memory, the manner, and even the extent, to which these two systems interact is currently unknown. To address this question in the current study, participants encoded words under reward or non-reward conditions, then one half of the participants were stressed using the social evaluation cold pressor task and the other half completed a non-stress control task. After a two-hour delay, all participants received a free recall and recognition memory test. There were no significant effects of stress or reward on overall memory performance. However, for the non-reward items, increases in stress-related cortisol in stressed participants were related to increases in recall and increases in recollection-based recognition responses. In contrast, for the reward items, increases in stress-related cortisol were not related to increases in memory performance. The results indicate that the stress and the reward systems interact in the way they impact episodic memory. The results are consistent with tag and capture models in the sense that cortisol reactivity can only affect non-reward items because plasticity-related products are already provided by reward anticipation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.

    Science.gov (United States)

    Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin

    2016-09-01

    Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene

  2. Early experience of a novel-environment in isolation primes a fearful phenotype characterized by persistent amygdala activation.

    Science.gov (United States)

    Daskalakis, Nikolaos P; Diamantopoulou, Anastasia; Claessens, Sanne E F; Remmers, Elisa; Tjälve, Marika; Oitzl, Melly S; Champagne, Danielle L; de Kloet, E Ronald

    2014-01-01

    Prolonged maternal separation (MS) activates the neonate's hypothalamus-pituitary-adrenal axis causing elevated basal and stress-induced corticosterone levels that may initiate amygdala-dependent fear learning. Here we test the hypothesis that the adult fearful phenotype is programmed by the pup's stressful experience during prolonged MS rather than by prolonged maternal absence per se. For this purpose, Wistar rat pups were exposed, on postnatal-day (pnd) 3, to: (i) repeated-MS in home-environment (HOME-SEP), 8h-MS daily for three days with the pups remaining together in the home-cage; (ii) repeated-MS in a novel-environment (NOVEL-SEP), with the same separation procedure, but now the pups were individually housed in a novel-environment during the 8h dam's absence; (iii) repeated handling, which consisted of daily brief (15 min instead of 8h) MS in the home-altogether or in a novel-environment individually (HOME-HAN and NOVEL-HAN, respectively); (iv) no-separation/no-handling (NON-SEP/NON-HAN) control condition, in which pups were left undisturbed in their home-cage. Compared to HOME-SEP rats, the NOVEL-SEP rats showed one day after the last MS enhanced stress-induced amygdala c-Fos expression and ACTH-release, despite of reduced adrenal corticosterone secretion. The higher amygdala c-Fos expression, ACTH-release and reduced corticosterone output observed postnatally, persisted into adulthood of the NOVEL-SEP animals. Behaviorally, NOVEL-SEP juvenile rats displayed deficits in social play, had intact spatial memory in the peri-pubertal period and showed more contextual fear memory compared to HOME-SEP in adulthood. Finally, NOVEL-HAN, compared to HOME-HAN, displayed increased stress-induced corticosterone output, no deficits in social play and reduced contextual fear. In conclusion, programming of an adult fearful phenotype linked to amygdala priming develops if pups are repeatedly isolated from peers in a novel-environment, while away from the dam for a prolonged

  3. A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

    Science.gov (United States)

    Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

    Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

  4. Stress during adolescence increases novelty seeking and risk taking behavior in male and female rats

    Directory of Open Access Journals (Sweden)

    Maria eToledo

    2011-04-01

    Full Text Available Adolescence is a period of major physical, hormonal and psychological change. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Likewise, stress during adolescence is associated with the development of psychiatric disorders later in life. Previously, using a rat model of psychogenic stress (exposure to predator odor followed by placement on an elevated platform during the pre-pubertal period (postnatal days 28-30, we reported sex-specific effects on auditory and contextual fear conditioning. Here, we study the short-term impact of psychogenic stress before and during puberty (postnatal days 28-42 on behavior (novelty seeking, risk taking, anxiety and depression and hypothalamus-pituitary-adrenocortical (HPA axis activation during late adolescence (postnatal days 45-51. Peri-pubertal stress decreased anxiety-like behavior and increased risk taking and novelty seeking behaviors during late adolescence (measured with the elevated plus maze, open field and exposure to novel object tests and intake of chocopop pellets before or immediate after stress. Finally neither depressive-like behavior (measured at the forced swim test nor HPA response to stress (blood corticosterone and glucose were affected by peri-pubertal stress. Nevertheless, when controlling for the basal anxiety of the mothers, animals exposed to peri-pubertal stress showed a significant decrease in corticosterone levels immediate after an acute stressor. The results from this study suggest that exposure to mild stressors during the peri-pubertal period induces a broad spectrum of behavioral changes in late adolescence, which may exacerbate the independence-building behaviors naturally happening during this transitional period (increase in curiosity, sensation-seeking and risk taking behaviors.

  5. Moderate altitude but not additional endurance training increases markers of oxidative stress in exhaled breath condensate.

    Science.gov (United States)

    Heinicke, Ilmar; Boehler, Annette; Rechsteiner, Thomas; Bogdanova, Anna; Jelkmann, Wolfgang; Hofer, Markus; Rawlings, Pablo; Araneda, Oscar F; Behn, Claus; Gassmann, Max; Heinicke, Katja

    2009-07-01

    Oxidative stress occurs at altitude, and physical exertion might enhance this stress. In the present study, we investigated the combined effects of exercise and moderate altitude on redox balance in ten endurance exercising biathletes, and five sedentary volunteers during a 6-week-stay at 2,800 m. As a marker for oxidative stress, hydrogen peroxide (H(2)O(2)) was analyzed by the biosensor measuring system Ecocheck, and 8-iso prostaglandin F2alpha (8-iso PGF2alpha) was determined by enzyme immunoassay in exhaled breath condensate (EBC). To determine the whole blood antioxidative capacity, we measured reduced glutathione (GSH) enzymatically using Ellman's reagent. Exercising athletes and sedentary volunteers showed increased levels of oxidative markers at moderate altitude, contrary to our expectations; there was no difference between both groups. Therefore, all subjects' data were pooled to examine the oxidative stress response exclusively due to altitude exposure. H(2)O(2) levels increased at altitude and remained elevated for 3 days after returning to sea level (p altitude, but declined immediately after returning to sea level (p altitude resulted in elevated GSH levels (p altitude (p altitude for up to 6 weeks increases markers of oxidative stress in EBC independent of additional endurance training. Notably, this oxidative stress is still detectable 3 days upon return to sea level.

  6. Prefrontal-amygdala fear networks come into focus

    Directory of Open Access Journals (Sweden)

    Maithe eArruda-Carvalho

    2015-10-01

    Full Text Available The ability to form associations between aversive threats and their predictors is fundamental to survival. However, fear and anxiety in excess are detrimental and are a hallmark of psychiatric diseases such as post-traumatic stress disorder (PTSD. PTSD symptomatology includes persistent and intrusive thoughts of an experienced trauma, suggesting an inability to downregulate fear when a corresponding threat has subsided. Convergent evidence from human and rodent studies supports a role for the medial prefrontal cortex (mPFC-amygdala network in both PTSD and the regulation of fear memory expression. In particular, current models stipulate that the prelimbic and infralimbic subdivisions of the rodent mPFC bidirectionally regulate fear expression via differential recruitment of amygdala neuronal subpopulations. However, an array of recent studies that employ new technical approaches has fundamentally challenged this interpretation. Here we explore how a new emphasis on the contribution of inhibitory neuronal populations, subcortical structures and the passage of time is reshaping our understanding of mPFC-amygdala circuits and their control over fear.

  7. DETECTING FOREST STRESS AND DECLINE IN RESPONSE TO INCREASING RIVER FLOW IN SOUTHWEST FLORIDA, USA

    Science.gov (United States)

    Forest stress and decline resulting from increased river flows were investigated in Myakka River State Park (MRSP), Florida, USA. Since 1977, land-use changes around the upper Myakka River watershed have resulted in significant increases in water entering the river, which have...

  8. Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations.

    Science.gov (United States)

    Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

    2017-01-01

    Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated

  9. Increased sensitivity to salt stress in tocopherol-deficient Arabidopsis mutants growing in a hydroponic system

    Science.gov (United States)

    Ellouzi, Hasna; Hamed, Karim Ben; Cela, Jana; Müller, Maren; Abdelly, Chedly; Munné-Bosch, Sergi

    2013-01-01

    Recent studies suggest that tocopherols could play physiological roles in salt tolerance but the mechanisms are still unknown. In this study, we analyzed changes in growth, mineral and oxidative status in vte1 and vte4 Arabidopsis thaliana mutants exposed to salt stress. vte1 and vte4 mutants lack α-tocopherol, but only the vte1 mutant is additionally deficient in γ-tocopherol. Results showed that a deficiency in vitamin E leads to reduced growth and increased oxidative stress in hydroponically-grown plants. This effect was observed at early stages, not only in rosettes but also in roots. The vte1 mutant was more sensitive to salt-induced oxidative stress than the wild type and the vte4 mutant. Salt sensitivity was associated with (i) high contents of Na+, (ii) reduced efficiency of PSII photochemistry (Fv/Fm ratio) and (iii) more pronounced oxidative stress as indicated by increased hydrogen peroxide and malondialdeyde levels. The vte 4 mutant, which accumulates γ- instead of α-tocopherol showed an intermediate sensitivity to salt stress between the wild type and the vte1 mutant. Contents of abscisic acid, jasmonic acid and the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid were higher in the vte1 mutant than the vte4 mutant and wild type. It is concluded that vitamin E-deficient plants show an increased sensitivity to salt stress both in rosettes and roots, therefore indicating the positive role of tocopherols in stress tolerance, not only by minimizing oxidative stress, but also controlling Na+/K+ homeostasis and hormonal balance. PMID:23299430

  10. Factors that Determine the Non-Linear Amygdala Influence on Hippocampus-Dependent Memory

    OpenAIRE

    Akirav, Irit; Richter-Levin, Gal

    2006-01-01

    Stressful experiences are known to either improve or impair hippocampal-dependent memory tasks and synaptic plasticity. These positive and negative effects of stress on the hippocampus have been largely documented, however little is known about the mechanism involved in the twofold influence of stress on hippocampal functioning and about what factors define an enhancing or inhibitory outcome. We have recently demonstrated that activation of the basolateral amygdala can produce a biphasic effe...

  11. Increase in Operator's Sympathetic Nerve Activity during Complicated Hepatobiliary Surgery: Evidence for Surgeons' Mental Stress.

    Science.gov (United States)

    Yamanouchi, Kosho; Hayashida, Naomi; Kuba, Sayaka; Sakimura, Chika; Kuroki, Tamotsu; Togo, Michita; Katayama, Noritada; Takamura, Noboru; Eguchi, Susumu

    2015-11-01

    Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances.

  12. Potassium and zinc increase tolerance to salt stress in wheat (Triticum aestivum L.).

    Science.gov (United States)

    Jan, Amin Ullah; Hadi, Fazal; Midrarullah; Nawaz, Muhammad Asif; Rahman, Khaista

    2017-07-01

    Potassium and zinc are essential elements in plant growth and metabolism and plays a vital role in salt stress tolerance. To investigate the physiological mechanism of salt stress tolerance, a pot experiment was conducted. Potassium and zinc significantly minimize the oxidative stress and increase root, shoot and spike length in wheat varieties. Fresh and dry biomass were significantly increased by potassium followed by zinc as compared to control C. The photosynthetic pigment and osmolyte regulator (proline, total phenolic, and total carbohydrate) were significantly enhanced by potassium and zinc. Salt stress increases MDA content in wheat varieties while potassium and zinc counteract the adverse effect of salinity and significantly increased membrane stability index. Salt stress decreases the activities of antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase) while the exogenous application of potassium and zinc significantly enhanced the activities of these enzymes. A significant positive correlation was found of spike length with proline (R 2  = 0.966 ∗∗∗ ), phenolic (R 2  = 0.741 ∗ ) and chlorophyll (R 2  = 0.853 ∗∗ ). The MDA content showed significant negative correlation (R 2  = 0.983 ∗∗∗ ) with MSI. It is concluded that potassium and zinc reduced toxic effect of salinity while its combine application showed synergetic effect and significantly enhanced salt tolerance. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Maria Bayliak

    2017-01-01

    Full Text Available Alpha-ketoglutarate (AKG is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe2+ and Cu2+ but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG.

  14. 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

  15. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

    Science.gov (United States)

    Hay, Colin W; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J; MacKenzie, Alasdair

    2014-09-01

    Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Stimulus Intensity-dependent Modulations of Hippocampal Long-term Potentiation by Basolateral Amygdala Priming

    Directory of Open Access Journals (Sweden)

    Zexuan eLi

    2012-05-01

    Full Text Available There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdalar modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP. We recently reported that while in CA1 basolateral amygdala (BLA priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG. However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, rasing the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1V, 50 µs pulse duration. In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1V or 2V, 100 µs pulse duration on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus.

  17. Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

    Science.gov (United States)

    Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

    2010-01-01

    In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

  18. Amygdala Signaling during Foraging in a Hazardous Environment.

    Science.gov (United States)

    Amir, Alon; Lee, Seung-Chan; Headley, Drew B; Herzallah, Mohammad M; Pare, Denis

    2015-09-23

    We recorded basolateral amygdala (BL) neurons in a seminaturalistic foraging task. Rats had to leave their nest to retrieve food in an elongated arena inhabited by a mechanical predator. There were marked trial-to-trial variations in behavior. After poking their head into the foraging arena and waiting there for a while, rats either retreated to their nest or initiated foraging. Before initiating foraging, rats waited longer on trials that followed failed than successful trials indicating that prior experience influenced behavior. Upon foraging initiation, most principal cells (Type-1) reduced their firing rate, while in a minority (Type-2) it increased. When rats aborted foraging, Type-1 cells increased their firing rates, whereas in Type-2 cells it did not change. Surprisingly, the opposite activity profiles of Type-1 and Type-2 units were also seen in control tasks devoid of explicit threats or rewards. The common correlate of BL activity across these tasks was movement velocity, although an influence of position was also observed. Thus depending on whether rats initiated movement or not, the activity of BL neurons decreased or increased, regardless of whether threat or rewards were present. Therefore, BL activity not only encodes threats or rewards, but is closely related to behavioral output. We propose that higher order cortical areas determine task-related changes in BL activity as a function of reward/threat expectations and internal states. Because Type-1 and Type-2 cells likely form differential connections with the central amygdala (controlling freezing), this process would determine whether movement aimed at attaining food or exploration is suppressed or facilitated. Significance statement: For decades, amygdala research has been dominated by pavlovian and operant conditioning paradigms. This work has led to the view that amygdala neurons signal threats or rewards, in turn causing defensive or approach behaviors. However, the artificial circumstances of

  19. Depression/anxiety disorder and amygdala

    International Nuclear Information System (INIS)

    Iidaka, Tetsuya

    2007-01-01

    Described and discussed are neuro-imaging studies on the amygdala (Am) concerning its volume, neuro-active drug effect on it and its response to repulsive and attractive stress-evoked character/temperament tests in patients mainly with major depression (MD) and anxiety disorder (AD), by functional MRI (fMRI) and positron emission tomography (PET). A recent trend of volumetry of Am is the voxel-based morphometry by MRI, of which results are still controversial in MD. In contrast, many studies by PET and fMRI using neuro-active drugs have revealed that Am activity in MD is stimulated, and this hyperactivity can be improved by anti-depressive drugs. In addition, difference of activities is suggested in Am left and right hemispheres. The hyperactivity in Am has been reported also in AD and phobic disorders, of which symptoms are conceivably expressed by the sensitivity changes in the cerebral limbic system involving Am. The author considers the central region responsible for the depressive mood is present around cortex of anteroinferior genu of corpus callosum where neuro-network with Am is dense. (R.T.)

  20. Heat-stress increase under climate change twice as large in cities as in rural areas

    Science.gov (United States)

    Wouters, Hendrik; De Ridder, Koen; Poelmans, Lien; Willems, Patrick; Brouwers, Johan; Hosseinzadehtalaei, Parisa; Tabari, Hossein; Vanden Broucke, Sam; van Lipzig, Nicole P. M.; Demuzere, Matthias

    2017-04-01

    Urban areas, being warmer than their surroundings, are particularly vulnerable to global warming and associated increases in extreme temperatures. Yet ensemble climate-model projections are generally performed on a scale that is too coarse to represent the evolution of temperatures in cities. Here, for the first time, we combine a 35-year convection-permitting climate model integrations with information from an ensemble of general circulation models to assess heat stress in a typical densely populated mid-latitude maritime region. We show that the heat-stress increase for the mid-21st century is twice as large in cities compared to their surrounding rural areas. The exacerbation is driven by the urban heat island itself, its concurrence with heatwaves, and urban expansion. Cities experience a heat-stress multiplication by a factor 1.4 and 15 depending on the scenario. Remarkably, the future heat-stress surpasses everywhere the urban hot spots of today. Our novel insights exemplify the need to combine information from climate models, acting on different scales, for climate-change risk assessment in heterogeneous regions. Moreover, these results highlight the necessity for adaptation to increasing heat stress, especially in urban areas.

  1. The multitasking framework: the effects of increasing workload on acute psychobiological stress reactivity.

    Science.gov (United States)

    Wetherell, Mark A; Carter, Kirsty

    2014-04-01

    A variety of techniques exist for eliciting acute psychological stress in the laboratory; however, they vary in terms of their ease of use, reliability to elicit consistent responses and the extent to which they represent the stressors encountered in everyday life. There is, therefore, a need to develop simple laboratory techniques that reliably elicit psychobiological stress reactivity that are representative of the types of stressors encountered in everyday life. The multitasking framework is a performance-based, cognitively demanding stressor, representative of environments where individuals are required to attend and respond to several different stimuli simultaneously with varying levels of workload. Psychological (mood and perceived workload) and physiological (heart rate and blood pressure) stress reactivity was observed in response to a 15-min period of multitasking at different levels of workload intensity in a sample of 20 healthy participants. Multitasking stress elicited increases in heart rate and blood pressure, and increased workload intensity elicited dose-response increases in levels of perceived workload and mood. As individuals rarely attend to single tasks in real life, the multitasking framework provides an alternative technique for modelling acute stress and workload in the laboratory. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Joseph W McFadden

    Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

  3. Enhanced prefrontal-amygdala connectivity following childhood adversity as a protective mechanism against internalizing in adolescence.

    Science.gov (United States)

    Herringa, Ryan J; Burghy, Cory A; Stodola, Diane E; Fox, Michelle E; Davidson, Richard J; Essex, Marilyn J

    2016-07-01

    Much research has focused on the deleterious neurobiological effects of childhood adversity that may underlie internalizing disorders. While most youth show emotional adaptation following adversity, the corresponding neural mechanisms remain poorly understood. In this longitudinal community study, we examined the associations among childhood family adversity, adolescent internalizing symptoms, and their interaction on regional brain activation and amygdala/hippocampus functional connectivity during emotion processing in 132 adolescents. Consistent with prior work, childhood adversity predicted heightened amygdala reactivity to negative, but not positive, images in adolescence. However, amygdala reactivity was not related to internalizing symptoms. Furthermore, childhood adversity predicted increased fronto-amygdala connectivity to negative, but not positive, images, yet only in lower internalizing adolescents. Childhood adversity also predicted increased fronto-hippocampal connectivity to negative images, but was not moderated by internalizing. These findings were unrelated to adolescence adversity or externalizing symptoms, suggesting specificity to childhood adversity and adolescent internalizing. Together, these findings suggest that adaptation to childhood adversity is associated with augmentation of fronto-subcortical circuits specifically for negative emotional stimuli. Conversely, insufficient enhancement of fronto-amygdala connectivity, with increasing amygdala reactivity, may represent a neural signature of vulnerability for internalizing by late adolescence. These findings implicate early childhood as a critical period in determining the brain's adaptation to adversity, and suggest that even normative adverse experiences can have significant impact on neurodevelopment and functioning. These results offer potential neural mechanisms of adaptation and vulnerability which could be used in the prediction of risk for psychopathology following childhood

  4. PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

    Directory of Open Access Journals (Sweden)

    C Makena Hightower

    Full Text Available Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS, decreasing endothelial nitric oxide (NO production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1, a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity.

  5. AMYGDALA MICROCIRCUITS CONTROLLING LEARNED FEAR

    Science.gov (United States)

    Duvarci, Sevil; Pare, Denis

    2014-01-01

    We review recent work on the role of intrinsic amygdala networks in the regulation of classically conditioned defensive behaviors, commonly known as conditioned fear. These new developments highlight how conditioned fear depends on far more complex networks than initially envisioned. Indeed, multiple parallel inhibitory and excitatory circuits are differentially recruited during the expression versus extinction of conditioned fear. Moreover, shifts between expression and extinction circuits involve coordinated interactions with different regions of the medial prefrontal cortex. However, key areas of uncertainty remain, particularly with respect to the connectivity of the different cell types. Filling these gaps in our knowledge is important because much evidence indicates that human anxiety disorders results from an abnormal regulation of the networks supporting fear learning. PMID:24908482

  6. Ropivacaine and Bupivacaine prevent increased pain sensitivity without altering neuroimmune activation following repeated social defeat stress.

    Science.gov (United States)

    Sawicki, Caroline M; Kim, January K; Weber, Michael D; Jarrett, Brant L; Godbout, Jonathan P; Sheridan, John F; Humeidan, Michelle

    2018-03-01

    Mounting evidence indicates that stress influences the experience of pain. Exposure to psychosocial stress disrupts bi-directional communication pathways between the central nervous system and peripheral immune system, and can exacerbate the frequency and severity of pain experienced by stressed subjects. Repeated social defeat (RSD) is a murine model of psychosocial stress that recapitulates the immune and behavioral responses to stress observed in humans, including activation of stress-reactive neurocircuitry and increased pro-inflammatory cytokine production. It is unclear, however, how these stress-induced neuroimmune responses contribute to increased pain sensitivity in mice exposed to RSD. Here we used a technique of regional analgesia with local anesthetics in mice to block the development of mechanical allodynia during RSD. We next investigated the degree to which pain blockade altered stress-induced neuroimmune activation and depressive-like behavior. Following development of a mouse model of regional analgesia with discrete sensory blockade over the dorsal-caudal aspect of the spine, C57BL/6 mice were divided into experimental groups and treated with Ropivacaine (0.08%), Liposomal Bupivacaine (0.08%), or Vehicle (0.9% NaCl) prior to exposure to stress. This specific region was selected for analgesia because it is the most frequent location for aggression-associated pain due to biting during RSD. Mechanical allodynia was assessed 12 h after the first, third, and sixth day of RSD after resolution of the sensory blockade. In a separate experiment, social avoidance behavior was determined after the sixth day of RSD. Blood, bone marrow, brain, and spinal cord were collected for immunological analyses after the last day of RSD in both experiments following behavioral assessments. RSD increased mechanical allodynia in an exposure-dependent manner that persisted for at least one week following cessation of the stressor. Mice treated with either Ropivacaine or

  7. Cold stress improves the production of artemisinin depending on the increase in endogenous jasmonate.

    Science.gov (United States)

    Liu, Wanhong; Wang, Huanyan; Chen, Yupei; Zhu, Shunqin; Chen, Min; Lan, Xiaozhong; Chen, Guoping; Liao, Zhihua

    2017-05-01

    Previous publications reported that the artemisinin level was increased in Artemisia annua following a night-frost period. However, the molecular mechanism was not clear. In this study, we found that exogenous jasmonate (JA) effectively enhanced the freezing tolerance of A. annua. The JA biosynthetic genes (LOX1, LOX2, allene oxide cyclase [AOC], and jasmonate resistant 1 [JAR1]) were induced by cold stress, leading to an increase in endogenous JA in cold-treated A. annua. Increased endogenous JA enhanced the expression of three JA-responsive transcription factors, ethylene response factor 1, ethylene response factor 2, and octadecanoid-responsive AP2/ERF, all of which were reported to transcriptionally activate the expression of artemisinin biosynthetic genes, such as amorpha-4,11-diene synthase (ADS), CYP71AV1, DBR2, and aldehyde dehydrogenase 1 (ALDH1). Furthermore, the expression levels of the four artemisinin biosynthetic genes were also significantly increased under cold stress. Consequently, the levels of artemisinin and related secondary metabolites, such as dihydroartemisinic acid, artemisinin B, and artemisinic acid, were increased in A. annua under cold stress. Our study points to a molecular mechanism in which the production of artemisinin is regulated by cold stress in A. annua. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  8. Hippocampal Structural Plasticity Accompanies the Resulting Contextual Fear Memory Following Stress and Fear Conditioning

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D.; Molina, Victor A.

    2013-01-01

    The present research investigated the resulting contextual fear memory and structural plasticity changes in the dorsal hippocampus (DH) following stress and fear conditioning. This combination enhanced fear retention and increased the number of total and mature dendritic spines in DH. Intra-basolateral amygdala (BLA) infusion of midazolam prior to…

  9. Financial strain is associated with increased oxidative stress levels: the Women's Health and Aging Studies.

    Science.gov (United States)

    Palta, Priya; Szanton, Sarah L; Semba, Richard D; Thorpe, Roland J; Varadhan, Ravi; Fried, Linda P

    2015-01-01

    Elevated oxidative stress levels may be one mechanism contributing to poor health outcomes. Financial strain and oxidative stress are each predictors of morbidity and mortality, but little research has investigated their relationship. Community-dwelling older adults (n = 728) from the Women's Health and Aging Studies I and II were included in this cross-sectional analysis. Financial strain was ascertained as an ordinal response to: "At the end of the month, do you have more than enough money left over, just enough, or not enough?" Oxidative stress was measured using serum protein carbonyl concentrations. Linear regression was used to quantify the relationship between financial strain and oxidative stress. Participants who reported high financial strain exhibited 13.4% higher protein carbonyl concentrations compared to individuals who reported low financial strain (p = 0.002). High financial strain may be associated with increased oxidative stress, suggesting that oxidative stress could mediate associations between financial strain and poor health. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. A Benzimidazole Proton Pump Inhibitor Increases Growth and Tolerance to Salt Stress in Tomato

    Directory of Open Access Journals (Sweden)

    Michael J. Van Oosten

    2017-07-01

    Full Text Available Pre-treatment of tomato plants with micromolar concentrations of omeprazole (OP, a benzimidazole proton pump inhibitor in mammalian systems, improves plant growth in terms of fresh weight of shoot and roots by 49 and 55% and dry weight by 54 and 105% under salt stress conditions (200 mM NaCl, respectively. Assessment of gas exchange, ion distribution, and gene expression profile in different organs strongly indicates that OP interferes with key components of the stress adaptation machinery, including hormonal control of root development (improving length and branching, protection of the photosynthetic system (improving quantum yield of photosystem II and regulation of ion homeostasis (improving the K+:Na+ ratio in leaves and roots. To our knowledge OP is one of the few known molecules that at micromolar concentrations manifests a dual function as growth enhancer and salt stress protectant. Therefore, OP can be used as new inducer of stress tolerance to better understand molecular and physiological stress adaptation paths in plants and to design new products to improve crop performance under suboptimal growth conditions.Highlight: Omeprazole enhances growth of tomato and increases tolerance to salinity stress through alterations of gene expression and ion uptake and transport.

  11. Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.

    Science.gov (United States)

    Kraehenmann, Rainer; Preller, Katrin H; Scheidegger, Milan; Pokorny, Thomas; Bosch, Oliver G; Seifritz, Erich; Vollenweider, Franz X

    2015-10-15

    The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change. This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart. Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state. These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Input from the Medial Geniculate Nucleus Modulates Amygdala Encoding of Fear Memory Discrimination

    Science.gov (United States)

    Ferrara, Nicole C.; Cullen, Patrick K.; Pullins, Shane P.; Rotondo, Elena K.; Helmstetter, Fred J.

    2017-01-01

    Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity…

  13. Meditation and yoga practice are associated with smaller right amygdala volume: the Rotterdam study

    NARCIS (Netherlands)

    R.A. Gotink (Rinske); M.W. Vernooij (Meike); M.K. Ikram (Kamran); W.J. Niessen (Wiro); Krestin, G.P. (Gabriel P.); A. Hofman (Albert); H.W. Tiemeier (Henning); M.G.M. Hunink (Myriam)

    2018-01-01

    textabstractTo determine the association between meditation and yoga practice, experienced stress, and amygdala and hippocampal volume in a large population-based study. This study was embedded within the population-based Rotterdam Study and included 3742 participants for cross-sectional

  14. Human amygdala reactivity is diminished by the beta-noradrenergic antagonist propranolol

    NARCIS (Netherlands)

    Hurlemann, R.; Walter, H.; Rehme, A. K.; Kukolja, J.; Santoro, S. C.; Schmidt, C.; Schnell, K.; Musshoff, F.; Keysers, C.; Maier, W.; Kendrick, K. M.; Onur, O. A.

    Background. Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy

  15. Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro

    NARCIS (Netherlands)

    Bijlsma, P. B.; van Raaij, M. T.; Dobbe, C. J.; Timmerman, A.; Kiliaan, A. J.; Taminiau, J. A.; Groot, J. A.

    2001-01-01

    Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to

  16. Ageing increases the sensitivity of neem (Azadirachta indica) seeds to imbibitional stress

    NARCIS (Netherlands)

    Neya, O.; Golovina, E.A.; Nijsse, J.; Hoekstra, F.A.

    2004-01-01

    Imbibitional stress was imposed on neem (Azadirachta indica) seeds by letting them soak for 1 h in water at unfavourable, low temperatures before further incubation at 30degreesC. Sensitivity to low imbibition temperatures increased with a decrease in seed moisture content (MC). To investigate a

  17. Climatic stress increases forest fire severity across the western United States

    Science.gov (United States)

    Phillip J. van Mantgem; Jonathan C.B. Nesmith; MaryBeth Keifer; Eric E. Knapp; Alan Flint; Lorriane Flint

    2013-01-01

    Pervasive warming can lead to chronic stress on forest trees, which may contribute to mortality resulting from fire-caused injuries. Longitudinal analyses of forest plots from across the western US show that high pre-fire climatic water deficit was related to increased post-fire tree mortality probabilities. This relationship between climate and fire was present after...

  18. Metabotropic glutamate receptor subtype 7 ablation causes dysregulation of the HPA axis and increases hippocampal BDNF protein levels: implications for stress-related psychiatric disorders.

    Science.gov (United States)

    Mitsukawa, Kayo; Mombereau, Cedric; Lötscher, Erika; Uzunov, Doncho P; van der Putten, Herman; Flor, Peter J; Cryan, John F

    2006-06-01

    Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety. For instance, mice with a targeted deletion of the gene for mGluR7 (mGluR7-/-) showed antidepressant and anxiolytic-like effects in a variety of stress-related paradigms, including the forced swim stress and the stress-induced hyperthermia tests. Deletion of mGluR7 reduces also amygdala- and hippocampus-dependent conditioned fear and aversion responses. Since the hypothalamic-pituitary-adrenal (HPA) axis regulates the stress response we investigate whether parameters of the HPA axis at the levels of selected mRNA transcripts and endocrine hormones are altered in mGluR7-deficient mice. Over all, mGluR7-/- mice showed only moderately lower serum levels of corticosterone and ACTH compared with mGluR7+/+ mice. More strikingly however, we found strong evidence for upregulated glucocorticoid receptor (GR)-dependent feedback suppression of the HPA axis in mice with mGluR7 deficiency: (i) mRNA transcripts of GR were significantly upregulated in the hippocampus of mGluR7-/- animals, (ii) similar increases were seen with 5-HT1A receptor transcripts, which are thought to be directly controlled by the transcription factor GR and finally (iii) mGluR7-/- mice showed elevated sensitivity to dexamethasone-induced suppression of serum corticosterone when compared with mGluR7+/+ animals. These results indicate that mGluR7 deficiency causes dysregulation of HPA axis parameters, which may account, at least in part, for the phenotype of mGluR7-/- mice in animal models for anxiety and depression. In addition, we present evidence that protein levels of brain-derived neurotrophic factor are also elevated in the hippocampus of mGluR7-/- mice, which we discuss in the context of the antidepressant-like phenotype found in those animals. We conclude that genetic ablation of m

  19. Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

    Directory of Open Access Journals (Sweden)

    Isabella M. Fuentes

    2016-12-01

    Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

  20. Hypoxia increases the behavioural activity of schooling herring: a response to physiological stress or respiratory distress?

    DEFF Research Database (Denmark)

    Herbert, Neill A.; Steffensen, John F.

    2006-01-01

    a deviation in physiological homeostasis is associated with any change in behavioural activity, we exposed C. harengus in a school to a progressive stepwise decline in water oxygen pressure  and measured fish swimming speed and valid indicators of primary and secondary stress (i.e. blood cortisol, lactate......Atlantic herring, Clupea harengus, increase their swimming speed during low O2 (hypoxia) and it has been hypothesised that the behavioural response is modulated by the degree of "respiratory distress" (i.e. a rise in anaerobic metabolism and severe physiological stress). To test directly whether...

  1. Effect of Trinexapac-ethyl on Increased Resistance to Drought Stress in Wheatgrass (Agropyron desertorum L.

    Directory of Open Access Journals (Sweden)

    mohamad hossein sheikh mohamadi

    2017-10-01

    Full Text Available Introduction: Drought is one of the most detrimental abiotic stresses for turfgrass growth across a wide range of geographic locations. Most cool-season grass species are not well adapted to extended periods of drought, particularly during summer months. Decline in turf quality caused by drought stress is a major concern in turfgrass culture. Therefore, developing management practices for improving drought resistance of turfgrasses has become essential in arid and semi-arid regions, especially during water use restriction. One strategy to improve plant drought resistance is to promote drought avoidance by reducing water loss during drought, which may be achieved by slowing growth rate of shoots and lowering leaf area canopy to reduce demand for water. Application of growth regulators is one of the methods for increasing resistance of plants to biotic and abiotic stresses. Trinexapac-ethyl (TE is one of the most widely used PGRs in the management of cool-season and warm-season turfgrass species. TE absorbed quickly by foliage and slow cell elongation through inhibiting of converting one form of gibberellic acid (GA20 to another (GA1. Most studies conducted under non-stressed conditions found that TE application increased chlorophyll content, turf quality, turf density and reduced shoot extension rate. We hypothesized that TE may influence plant tolerance to drought stress. Limited available data─ as reported in the above referred studies─ suggest that TE application may be beneficial for plant tolerance to stresses, but the effectiveness varies with turfgrass species, dose and duration of TE treatment, and type of stress. The main aim of this research is to evaluate the effect of Trinexapac-ethyl on increased resistance to drought stress in wheatgrass. Materials and Methods: Wheatgrass (Agropyron desertorum L. was used in this study. This study was conducted in field conditions at Isfahan University of Technology, Isfahan, Iran.. Wheatgrass

  2. Differential activation of amygdala, dorsal and ventral hippocampus following an exposure to a reminder ofunderwater trauma

    Directory of Open Access Journals (Sweden)

    Gilad eRitov

    2014-01-01

    Full Text Available Recollection of emotional memories is attributed in part to the activation of the amygdala and the hippocampus. Recent hypothesis suggest a pivotal role for the ventral hippocampus in traumatic stress processing and emotional memory retrieval. Persistent re-experiencing and intrusive recollections are core symptoms in acute and posttraumatic stress disorders (ASD; PTSD. Such intrusive recollections are often triggered by reminders associated with the trauma.We examined the impact of exposure to a trauma reminder (under water trauma on the activation of the basolateral amygdala (BLA, dorsal and ventral hippocampus. Rats were exposed to underwater trauma and 24 hours later were re-exposed to the context of the trauma. Phosphorylation of the extracellular signal-regulated kinase (ERK was used as a marker for level of activation of these regions. Significant increase in ERK activation was found in the ventral hippocampus and BLA. Such pattern of activation was not found in animals exposed only to the trauma or in animals exposed only to the trauma reminder. Additionally, the dissociative pattern of activation of the ventral hippocampus sub-regions positively correlated with the activation of the BLA.Our findings suggest a specific pattern of neural activation during recollection of a trauma reminder, with a unique contribution of the ventral hippocampus. Measured 24 hrs after the exposure to the traumatic experience, the current findings relate to relatively early stages of traumatic memory consolidation. Understanding the neural mechanisms underlying these initial stages may contribute to developing intervention strategies that could reduce the risk of eventually developing PTSD.

  3. Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

    Science.gov (United States)

    Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

    2015-11-01

    It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the

  4. The Amygdala and the Relevance Detection Theory of Autism: An Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Tiziana eZalla

    2013-12-01

    Full Text Available In the last few decades, there has been increasing interest in the role of the amygdala in psychiatric disorders and in particular its contribution to the socio-emotional impairments in autism spectrum disorders (ASDs. Given that the amygdala is a component structure of the social brain, several theoretical explanations compatible with amygdala dysfunction have been proposed to account for socio-emotional impairments in ASDs, including abnormal eye contact, gaze monitoring, face processing, mental state understanding and empathy. Nevertheless, many theoretical accounts, based on the Amygdala Theory of Autism, fail to elucidate the complex pattern of impairments observed in this population, which extends beyond the social domain. As posited by the Relevance Detector theory (Sander, Grafman and Zalla, 2003, the human amygdala is a critical component of a brain circuit involved in the appraisal of self-relevant events that include, but are not restricted to, social stimuli. Here, we propose that the behavioral and social-emotional features of ASDs may be better understood in terms of a disruption in a ‘Relevance Detector Network’ affecting the processing of stimuli that are relevant for the organism’s self-regulating functions. In the present review, we will first summarize the main literature supporting the involvement of the amygdala in socio-emotional disturbances in ASDs. Next, we will present a revised version of the amygdala Relevance Detector hypothesis and we will show that this theoretical framework can provide a better understanding of the heterogeneity of the impairments and symptomatology of ASDs. Finally, we will discuss some predictions of our model, and suggest new directions in the investigation of the role of the amygdala within the more generally disrupted cortical connectivity framework as a model of neural organization of the autistic brain.

  5. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Genaro Gabriel Ortiz

    2009-01-01

    Full Text Available Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old and 7 men (5 aged from 20 to 30 and 2 were > 40 years old fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites, lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals, and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.

  6. Increased salivary oxidative stress parameters in patients with type 2 diabetes: Relation with periodontal disease.

    Science.gov (United States)

    Arana, Carlos; Moreno-Fernández, Ana María; Gómez-Moreno, Gerardo; Morales-Portillo, Cristóbal; Serrano-Olmedo, Isabel; de la Cuesta Mayor, M Carmen; Martín Hernández, Tomás

    2017-05-01

    The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (Pperiodontal health. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Dopamine in the medial amygdala network mediates human bonding.

    Science.gov (United States)

    Atzil, Shir; Touroutoglou, Alexandra; Rudy, Tali; Salcedo, Stephanie; Feldman, Ruth; Hooker, Jacob M; Dickerson, Bradford C; Catana, Ciprian; Barrett, Lisa Feldman

    2017-02-28

    Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers' dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the "medial amygdala network") that supports social functioning. We also measured the mothers' behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother's infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.

  8. Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

    Science.gov (United States)

    Elzinga, B M; Bremner, J D

    2002-06-01

    A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed.

  9. Working the night shift causes increased vascular stress and delayed recovery in young women.

    Science.gov (United States)

    Lo, Shih-Hsiang; Lin, Lian-Yu; Hwang, Jing-Shiang; Chang, Yu-Yin; Liau, Chiau-Suong; Wang, Jung-Der

    2010-08-01

    Shiftwork has been associated with elevated blood pressure (BP) and decreased heart-rate variability (HRV), factors that may increase the long-term risk of cardiovascular-related mortality and morbidity. This study explored the effect of shiftwork on dynamic changes in autonomic control of HRV (cardiac stress), systolic BP and diastolic BP, i.e., SBP and DBP (vascular stress), and recovery in the same subjects working different shifts. By studying the same subjects, the authors could reduce the effect of possible contribution of between-subject variation from genetic predisposition and environmental factors. The authors recruited 16 young female nurses working rotating shifts--day (08:00-16:00 h), evening (16:00-00:00 h), and night (00:00-08:00 h)--and 6 others working the regular day shift. Each nurse received simultaneous and repeated 48-h ambulatory electrocardiography and BP monitoring during their work day and the following off-duty day. Using a linear mixed-effect model to adjust for day shift, the results of the repeated-measurements and self-comparisons found significant shift differences in vascular stress. While working the night shift, the nurses showed significant increases in vascular stress, with increased SBP of 9.7 mm Hg. The changes of SBP and DBP seemed to peak during waking time at the same time on the day off as they did on the working day. Whereas HRV profiles usually returned to baseline level after each shift, the SBP and DBP of night-shift workers did not completely return to baseline levels the following off-duty day (p night shift, they do not completely recover from increases in vascular stress on that day.

  10. Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

    2017-03-15

    A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

  11. Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism.

    Science.gov (United States)

    Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K; Lehtonen, Jukka Y A

    2016-04-20

    As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. The association between rotating shift work and increased occupational stress in nurses.

    Science.gov (United States)

    Lin, Pei-Chen; Chen, Chung-Hey; Pan, Shung-Mei; Chen, Yao-Mei; Pan, Chih-Hong; Hung, Hsin-Chia; Wu, Ming-Tsang

    2015-01-01

    The aim of this study was to investigate whether rotating shift work increases occupational stress in nurses. This study measured shift work scheduling and occupational stress by using the Effort-Reward Imbalance model with self-reported questionnaires in a sample of 654 female nurses. Overcommitment risk was higher in nurses who worked rotating shifts than in those who worked day/non-night shifts (OR, 2.16; 95% CI, 1.03-4.66). However, an effort/reward imbalance was not directly associated with work schedules (OR, 1.88; 95% CI, 0.87-4.35). Among nurses working rotation rotating shifts, those who had 2 days off after their most recent night shifts showed an alleviated risk of overcommitment (OR, 0.52; 95% CI, 0.32-0.82), but those who had worked for at least one series of 7 consecutive work days per month had an increased risk of effort/reward imbalance (OR, 2.75; 95% CI, 1.69-4.48). Additionally, those who had little or no participation in planning working hours and shift scheduling and worked overtime at least three times per week during the preceding 2 months tended to have high stress. The nurses who worked rotating shifts tended to experience work-related stress, but their stress levels improved if they had at least 2 days off after their most recent night shift and if they were not scheduled to work 7 consecutive days. These empirical data can be used to optimize work schedules for nurses to alleviate work stress.

  13. Chronic stress undermines the compensatory sleep efficiency increase in response to sleep restriction in adolescents.

    Science.gov (United States)

    Astill, Rebecca G; Verhoeven, Dorit; Vijzelaar, Romy L; Van Someren, Eus J W

    2013-08-01

    To investigate the effects of real-life stress on the sleep of adolescents, we performed a repeated-measures study on actigraphic sleep estimates and subjective measures during one regular school week, two stressful examination weeks and a week's holiday. Twenty-four adolescents aged 17.63 ± 0.10 years (mean ± standard error of the mean) wore actigraphs and completed diaries on subjective stress, fatigue, sleep quality, number of examinations and consumption of caffeine and alcohol for 4 weeks during their final year of secondary school. The resulting almost 500 assessments were analysed using mixed-effect models to estimate the effects of mere school attendance and additional examination stress on sleep estimates and subjective ratings. Total sleep time decreased from 7:38 h ± 12 min during holidays to 6:40 h ± 12 min during a regular school week. This 13% decrease elicited a partial compensation, as indicated by a 3% increase in sleep efficiency and a 6% decrease in the duration of nocturnal awakenings. During examination weeks total sleep time decreased to 6:23 h ± 8 min, but it was now accompanied by a decrease in sleep efficiency and subjective sleep quality and an increase in wake bout duration. In conclusion, school examination stress affects the sleep of adolescents. The compensatory mechanism of more consolidated sleep, as elicited by the sleep restriction associated with mere school attendance, collapsed during 2 weeks of sustained examination stress. © 2013 European Sleep Research Society.

  14. Direction of Amygdala-Neocortex Interaction During Dynamic Facial Expression Processing.

    Science.gov (United States)

    Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshikawa, Sakiko; Toichi, Motomi

    2017-03-01

    Dynamic facial expressions of emotion strongly elicit multifaceted emotional, perceptual, cognitive, and motor responses. Neuroimaging studies revealed that some subcortical (e.g., amygdala) and neocortical (e.g., superior temporal sulcus and inferior frontal gyrus) brain regions and their functional interaction were involved in processing dynamic facial expressions. However, the direction of the functional interaction between the amygdala and the neocortex remains unknown. To investigate this issue, we re-analyzed functional magnetic resonance imaging (fMRI) data from 2 studies and magnetoencephalography (MEG) data from 1 study. First, a psychophysiological interaction analysis of the fMRI data confirmed the functional interaction between the amygdala and neocortical regions. Then, dynamic causal modeling analysis was used to compare models with forward, backward, or bidirectional effective connectivity between the amygdala and neocortical networks in the fMRI and MEG data. The results consistently supported the model of effective connectivity from the amygdala to the neocortex. Further increasing time-window analysis of the MEG demonstrated that this model was valid after 200 ms from the stimulus onset. These data suggest that emotional processing in the amygdala rapidly modulates some neocortical processing, such as perception, recognition, and motor mimicry, when observing dynamic facial expressions of emotion. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety.

    Science.gov (United States)

    Makovac, Elena; Watson, David R; Meeten, Frances; Garfinkel, Sarah N; Cercignani, Mara; Critchley, Hugo D; Ottaviani, Cristina

    2016-11-01

    Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology. © The Author (2016). Published by Oxford University Press.

  16. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

    Science.gov (United States)

    Paret, Christian; Ruf, Matthias; Gerchen, Martin Fungisai; Kluetsch, Rosemarie; Demirakca, Traute; Jungkunz, Martin; Bertsch, Katja; Schmahl, Christian; Ende, Gabriele

    2016-01-15

    Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: pneurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Volumetric analysis of the hypothalamus, amygdala and hippocampus in non-suicidal and suicidal mood disorder patients--a post-mortem study.

    Science.gov (United States)

    Bielau, Hendrik; Brisch, Ralf; Gos, Tomasz; Dobrowolny, Henrik; Baumann, Bruno; Mawrin, Christian; Kreutzmann, Peter; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

    2013-11-01

    In recent years, the hypothalamus, amygdala and hippocampus have attracted increased interest with regard to the effects of stress on neurobiological systems in individuals with depression and suicidal behaviour. A large body of evidence indicates that these subcortical regions are involved in the pathogenetic mechanisms of mood disorders and suicide. The current neuroimaging techniques inadequately resolve the structural components of small and complex brain structures. In previous studies, our group was able to demonstrate a structural and neuronal pathology in mood disorders. However, the impact of suicide remains unclear. In the current study we used volumetric measurements of serial postmortem sections with combined Nissl-myelin staining to investigate the hypothalamus, amygdala and hippocampus in suicide victims with mood disorders (n = 11), non-suicidal mood disorder patients (n = 9) and control subjects (n = 23). Comparisons between the groups by using an ANCOVA showed a significant overall difference for the hypothalamus (p = 0.001) with reduced volumes in non-suicidal patients compared to suicide victims (p = 0.018) and controls (p = 0.006). To our surprise, the volumes between the suicide victims and controls did not differ significantly. For the amygdala and hippocampus no volume changes between the groups could be detected (all p values were n. s.). In conclusion our data suggest a structural hypothalamic pathology in non-suicidal mood disorder patients. The detected differences between suicidal and non-suicidal patients suggest that suicidal performances might be related to the degree of structural deficits.

  18. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability

    Directory of Open Access Journals (Sweden)

    Karin ede Punder

    2015-05-01

    Full Text Available Chronic non-communicable diseases (NCDs are the leading causes of work absence, disability and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here we hypothesize that stresses (defined as homeostatic disturbances can induce low-grade inflammation by increasing the availability of water, sodium and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases.

  19. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    Science.gov (United States)

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  20. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  1. The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

    Science.gov (United States)

    Bliss-Moreau, Eliza; Moadab, Gilda; Santistevan, Anthony; Amaral, David G

    2017-03-30

    The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Acute social stress increases biochemical and self report markers of stress without altering spatial learning in humans.

    Science.gov (United States)

    Klopp, Christine; Garcia, Carlos; Schulman, Allan H; Ward, Christopher P; Tartar, Jaime L

    2012-01-01

    Spatial learning is shown to be influenced by acute stress in both human and other animals. However, the intricacies of this relationship are unclear. Based on prior findings we hypothesized that compared to a control condition, a social stress condition would not affect spatial learning performance despite elevated biochemical markers of stress. The present study tested the effects of social stress in human males and females on a subsequent spatial learning task. Social stress induction consisted of evaluative stress (the Trier Social Stress Test, TSST) compared to a placebo social stress. Compared to the placebo condition, the TSST resulted in significantly elevated cortisol and alpha amylase levels at multiple time points following stress induction. In accord, cognitive appraisal measures also showed that participants in the TSST group experienced greater perceived stress compared to the placebo group. However, there were no group differences in performance on a spatial learning task. Our findings suggest that unlike physiological stress, social stress does not result in alterations in spatial learning in humans. It is possible that moderate social evaluative stress in humans works to prevent acute stress-mediated alterations in hippocampal learning processes..

  3. [The effect of work-related stress on the occurrence of increased blood pressure].

    Science.gov (United States)

    Budaj, A; Cybulski, J; Kułakowski, P; Makowska, E; Rezler, J; Lange, J; Gorzkowska, J; Abramowski, S

    In 546 officials the arterial blood pressure was measured twice at the beginning and at the end of a working day, filling also an inquiry form. As hypertension systolic BP over 160 mm Hg (21.3 kPa) or more, and diastolic BP 96 mm Hg (12.7 kPa) or more were accepted. In 90 subjects (16.5%) above normal pressure values were found. Hypertension had been diagnosed previously in 50 subjects in this group (55.5%) but only 13 of them (26%) were treated systematically. Excessive stress of work was complained of by 62.6% of the subjects. Increased blood pressure was found significantly more frequently in the group perceiving excessive stress of work (19.9%) as compared to those not experiencing this stress (10.8%, p less than 0.1). In the group in managerial posts these proportions were 24.8% and 14.4% respectively (p less than 0.1). Blood pressure rise to abnormal levels during the working day occurred also significantly more frequently in the group experiencing it this was noted only in 1.6% of cases (p less than 0.5). The knowledge of own hypertension was very low in this group. These results indicate the necessity of increasing prophylactic measures in the form of greater frequency of control measurements of the blood pressure, better health education, and limitation of stress situations in working environment.

  4. Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dong Hou

    2018-07-01

    Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer

  5. Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.

    Science.gov (United States)

    Mullan, Lorna A; Mularczyk, Ewa J; Kung, Louise H; Forouhan, Mitra; Wragg, Jordan Ma; Goodacre, Royston; Bateman, John F; Swanton, Eileithyia; Briggs, Michael D; Boot-Handford, Raymond P

    2017-10-02

    The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture. Depending on the nature of the mutation, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal degradation, thereby reducing intracellular accumulation of mutant collagen. In MCDS mice expressing the Col10a1.pN617K mutation, CBZ reduced the MCDS-associated expansion of the growth plate hypertrophic zone, attenuated enhanced expression of ER stress markers such as Bip and Atf4, increased bone growth, and reduced skeletal dysplasia. CBZ produced these beneficial effects by reducing the MCDS-associated abnormalities in hypertrophic chondrocyte differentiation. Stimulation of intracellular proteolysis using CBZ treatment may therefore be a clinically viable way of treating the ER stress-associated dwarfism MCDS.

  6. Oral sucrose for heel lance increases adenosine triphosphate use and oxidative stress in preterm neonates.

    Science.gov (United States)

    Asmerom, Yayesh; Slater, Laurel; Boskovic, Danilo S; Bahjri, Khaled; Holden, Megan S; Phillips, Raylene; Deming, Douglas; Ashwal, Stephen; Fayard, Elba; Angeles, Danilyn M

    2013-07-01

    To examine the effects of sucrose on pain and biochemical markers of adenosine triphosphate (ATP) degradation and oxidative stress in preterm neonates experiencing a clinically required heel lance. Preterm neonates that met study criteria (n = 131) were randomized into 3 groups: (1) control; (2) heel lance treated with placebo and non-nutritive sucking; and (3) heel lance treated with sucrose and non-nutritive sucking. Plasma markers of ATP degradation (hypoxanthine, xanthine, and uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured with the Premature Infant Pain Profile. Data were analyzed by the use of repeated-measures ANOVA and Spearman rho. We found significant increases in plasma hypoxanthine and uric acid over time in neonates who received sucrose. We also found a significant negative correlation between pain scores and plasma allantoin concentration in a subgroup of neonates who received sucrose. A single dose of oral sucrose, given before heel lance, significantly increased ATP use and oxidative stress in premature neonates. Because neonates are given multiple doses of sucrose per day, randomized trials are needed to examine the effects of repeated sucrose administration on ATP degradation, oxidative stress, and cell injury. Copyright © 2013 Mosby, Inc. All rights reserved.

  7. Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a nonforensic sample.

    Science.gov (United States)

    Yoder, Keith J; Porges, Eric C; Decety, Jean

    2015-04-01

    Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self-Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. © 2014 Wiley Periodicals, Inc.

  8. Finnish physicians' stress related to information systems keeps increasing: a longitudinal three-wave survey study.

    Science.gov (United States)

    Heponiemi, Tarja; Hyppönen, Hannele; Vehko, Tuulikki; Kujala, Sari; Aalto, Anna-Mari; Vänskä, Jukka; Elovainio, Marko

    2017-10-17

    Poorly functioning, time-consuming, and inadequate information systems are among the most important work-related psychosocial factors causing stress in physicians. The present study examined the trend in the perceived stress that was related to information systems (SRIS) among Finnish physicians during a nine-year follow-up. In addition, we examined the associations of gender, age, employment sector, specialization status, leadership position, on-call burden, and time pressure with SRIS change and levels. A longitudinal design with three survey data collection waves (2006, 2010 and 2015) based on a random sample of Finnish physicians in 2006 was used. The study sample included 1095 physicians (62.3% women, mean age 54.4 years) who provided data on SRIS in every wave. GLM repeated measures analyses were used to examine the associations between independent variables and the SRIS trend during the years 2006, 2010, and 2015. SRIS increased during the study period. The estimated marginal mean of SRIS in 2006 was 2.80 (95% CI = 2.68-2.92) and the mean increase was 0.46 (95% CI = 0.30-0.61) points from 2006 to 2010 and 0.25 (95% CI = 0.11-0.39) points from 2010 to 2015. Moreover, our results show that the increase was most pronounced in primary care, whereas in hospitals SRIS did not increase between 2010 and 2015. SRIS increased more among those in a leadership position. On-call duties and high time-pressures were associated with higher SRIS levels during all waves. Changing, difficult, and poorly functioning information systems (IS) are a prominent source of stress among Finnish physicians and this perceived stress continues to increase. Organizations should implement arrangements to ease stress stemming from IS especially for those with a high workload and on-call or leadership duties. To decrease IS-related stress, it would be important to study in more detail the main IS factors that contribute to SRIS. Earlier studies indicate that the usability and stability

  9. Amygdala Activity During Autobiographical Memory Recall in Depressed and Vulnerable Individuals: Association With Symptom Severity and Autobiographical Overgenerality.

    Science.gov (United States)

    Young, Kymberly D; Siegle, Greg J; Bodurka, Jerzy; Drevets, Wayne C

    2016-01-01

    In healthy individuals, autobiographical memory recall is biased toward positive and away from negative events, while the opposite is found in depressed individuals. This study examined amygdala activity during autobiographical memory recall as a putative mechanism underlying biased memory recall and depressive symptoms in currently depressed adults and two vulnerable populations: individuals remitted from depression and otherwise healthy individuals at high familial risk of developing depression. Identification of such vulnerability factors could enable interception strategies that prevent depression onset. Sixty healthy control subjects, 45 unmedicated currently depressed individuals, 25 unmedicated remitted depressed individuals, and 30 individuals at high familial risk of developing depression underwent functional MRI while recalling autobiographical memories in response to emotionally valenced cue words. Amygdala reactivity and connectivity with anatomically defined amygdala regions were examined. During positive recall, depressed participants exhibited significantly decreased left amygdala activity and decreased connectivity with regions of the salience network compared with the other groups. During negative recall, control subjects had significantly decreased left amygdala activity compared with the other groups, while depressed participants exhibited increased amygdala connectivity with the salience network. In depressed participants, left amygdala activity during positive recall correlated significantly with depression severity (r values >-0.38) and percent of positive specific memories recalled (r values >0.59). The results suggest that left amygdala hyperactivity during negative autobiographical recall is a trait-like marker of depression, as both vulnerable groups showed activity similar to the depressed group, while amygdala hypoactivity during positive autobiographical recall is a state marker of depression manifesting in active disease. Treatments

  10. Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval.

    Science.gov (United States)

    Janitzky, K; Peine, A; Kröber, A; Yanagawa, Y; Schwegler, H; Roskoden, T

    2014-10-01

    The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice. Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure. Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Amygdala activity associated with social choice in mice.

    Science.gov (United States)

    Mihara, Takuma; Mensah-Brown, Kobina; Sobota, Rosanna; Lin, Robert; Featherstone, Robert; Siegel, Steven J

    2017-08-14

    Studies suggest that the amygdala is a key region for regulation of anxiety, fear and social function. Therefore, dysfunction of the amygdala has been proposed as a potential mechanism for negative symptoms in schizophrenia. This may be due to NMDA receptor-mediated hypofunction, which is thought to be related to the pathogenesis of schizophrenia. In this study, electroencephalographic amygdala activity was assessed in mice during the three-chamber social test. This activity was also evaluated following exposure to the NMDA receptor antagonist ketamine. Vehicle-treated mice spent significantly more time in the social than the non-social chamber. This social preference was eliminated by ketamine. However, ketamine-treated mice spent significantly less time in the social chamber and significantly more time in the nonsocial chamber than vehicle-treated mice. There were no significant differences in induced powers between social and non-social chamber entries in vehicle-treated mice, except for theta frequencies, which featured greater induced theta power during non-social chamber entry. Ketamine eliminated differences in induced theta power between social and non-social chamber entries. Moreover, ketamine increased the induced gamma power during social chamber entry compared to that of vehicle-treated mice. All other frequency ranges were not significantly influenced by zone or drug condition. All significant findings were upon entry to chambers not during interaction. Results suggest that impaired function of NMDA receptor-mediated glutamate transmission can induce social impairments and amygdala dysfunction, similar to the pattern in schizophrenia. Future studies will utilize this method to evaluate mechanisms of social dysfunction and development of treatments of social impairments in schizophrenia. Copyright © 2017. Published by Elsevier B.V.

  12. Academic examination stress increases disordered eating symptomatology in female university students.

    Science.gov (United States)

    Costarelli, V; Patsai, A

    2012-09-01

    It is well documented that stress and anxiety can affect eating behaviour and food intake in humans. The purpose of the current study was to explore the possible effect of academic examination stress on disordered eating attitudes, emotional eating, restraint eating, body image, anxiety levels and self-esteem in a group of female university students. The interrelationships of the above parameters were also examined. Sixty Greek female university students, 18-25 years old, have been recruited and completed, on two separate occasions: a) during an examination stress period, and b) during a control period, the following questionnaires: the Eating Attitudes Test (EAT-26), the Dutch Eating Behavior Questionnaire (DEBQ), the State-Trait Anxiety Inventory (STAI), the Rosenberg Self- Esteem Scale, the Body Image Pictorial Instrument Scale (COLLINS) and a specially designed General Background Questionnaire. Subjects reported significantly higher levels of disordered eating attitudes (EAT-26, p=0.01), higher levels of anxiety (p=0.000) and lower levels of self-esteem (p=0.016) during the examination stress period compared to the control period. Disordered eating attitudes (EAT-26) were significantly positively correlated with emotional eating (p=0.04) and restrained eating (p=0.010) and negatively correlated with levels of self-esteem (p=0.05) and perceived desired body image (p=0.008) during the exam stress period. Finally, EAT-26 was significantly positively correlated with levels of anxiety in both study periods. Academic examination stress seems to increase disordered eating symptomatology in female university students and is associated with lower levels of self-esteem, an important finding which warrants further investigation.

  13. Midlife Work-Related Stress Increases Dementia Risk in Later Life: The CAIDE 30-Year Study.

    Science.gov (United States)

    Sindi, Shireen; Hagman, Göran; Håkansson, Krister; Kulmala, Jenni; Nilsen, Charlotta; Kåreholt, Ingemar; Soininen, Hilkka; Solomon, Alina; Kivipelto, Miia

    2017-10-01

    To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimer's disease later in life, in a large representative population. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders. Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimer's disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up. Midlife work-related stress increases the risk for MCI, dementia, and Alzheimer's disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Zinc release in the lateral nucleus of the amygdala by stimulation of the entorhinal cortex.

    Science.gov (United States)

    Takeda, Atsushi; Imano, Sachie; Itoh, Hiromasa; Oku, Naoto

    2006-11-06

    Zinc release in the lateral nucleus of the amygdala was examined using rat brain slices. The lateral and basolateral nuclei in the amygdala were evidently stained by Timm's sulfide-silver staining method. When the amygdala including both the nuclei was stimulated with 100 mM KCl by means of in vivo microdialysis, extracellular zinc concentration was increased significantly. Zinc release in the lateral nucleus of the amygdala innervated by the entorhinal cortex was next examined in brain slices double-stained with zinc and calcium indicators. Extracellular zinc signal (ZnAF-2) in the lateral nucleus was increased with intracellular calcium signal (calcium orange) during delivery of tetanic stimuli to the entorhinal cortex. Both the increases were completely inhibited by addition of 1 micro M tetrodotoxin, a sodium channel blocker. Furthermore, calcium signal in the lateral nucleus during delivery of tetanic stimuli to the entorhinal cortex was increased in the presence of 10 micro M CNQX, an AMPA/KA receptor antagonist, and this increase was facilitated by addition of 1 mM CaEDTA, a membrane-impermeable zinc chelator. The present study suggested that zinc is released in the lateral nucleus of the amygdala by depolarization of the entorhinal neurons. In the lateral nucleus, zinc released may suppress the increase in presynaptic calcium signal.

  15. The Amygdala: An Agent of Change in Adolescent Neural Networks

    Science.gov (United States)

    Scherf, K. Suzanne; Smyth, Joshua M.; Delgado, Mauricio R.

    2013-01-01

    A unique component of adolescent development is the need to master new developmental tasks in which peer interactions become primary (for the purposes of becoming autonomous from parents, forming intimate friendships, and romantic/sexual partnerships). Previously, it has been suggested that the ability to master these tasks requires an important re-organization in the relation between perceptual, motivational, affective, and cognitive systems in a very general and broad way that is fundamentally influenced by the infusion of sex hormones during pubertal development (Scherf et al., 2012). Herein, we extend this argument to suggest that the amygdala, which is vastly connected with cortical and subcortical regions and contains sex hormone receptors, may lie at the heart of this re-organization. We propose that during adolescent development there is a shift in the attribution of relevance to existing stimuli and contexts that is mediated by the amygdala (e.g., heightened relevance of peer faces, reduced relevance of physical distance from parents). As a result, amygdala inputs to existing stable neural networks are re-weighted (increased or decreased), which destabilizes the functional interactions among regions within these networks and allows for a critical restructuring of the network functional organization. This process of network re-organization enables processing of qualitatively new kinds of social information and the emergence of novel behaviors that support mastery of adolescent-specific developmental tasks. PMID:23756154

  16. Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity

    Science.gov (United States)

    Lapate, R. C.; Rokers, B.; Tromp, D. P. M.; Orfali, N. S.; Oler, J. A.; Doran, S. T.; Adluru, N.; Alexander, A. L.; Davidson, R. J.

    2016-01-01

    Conscious awareness of negative cues is thought to enhance emotion-regulatory capacity, but the neural mechanisms underlying this effect are unknown. Using continuous flash suppression (CFS) in the MRI scanner, we manipulated visual awareness of fearful faces during an affect misattribution paradigm, in which preferences for neutral objects can be biased by the valence of a previously presented stimulus. The amygdala responded to fearful faces independently of awareness. However, when awareness of fearful faces was prevented, individuals with greater amygdala responses displayed a negative bias toward unrelated novel neutral faces. In contrast, during the aware condition, inverse coupling between the amygdala and prefrontal cortex reduced this bias, particularly among individuals with higher structural connectivity in the major white matter pathway connecting the prefrontal cortex and amygdala. Collectively, these results indicate that awareness promotes the function of a critical emotion-regulatory network targeting the amygdala, providing a mechanistic account for the role of awareness in emotion regulation. PMID:27181344

  17. Violent Video Games Don't Increase Hostility in Teens, but They Do Stress Girls Out.

    Science.gov (United States)

    Ferguson, Christopher J; Trigani, Benjamin; Pilato, Steven; Miller, Stephanie; Foley, Kimberly; Barr, Hayley

    2016-03-01

    The impact of violent video games (VVGs) on youth remains unclear given inconsistent results in past literature. Most previous experimental studies have been done with college students, not youth. The current study examined the impact of VVGs in an experimental study of teens (12-18). Participants were randomized to play either a violent or non-violent video game. Teens also reported their levels of stress and hostility both before and after video game play. Hostility levels neither decreased nor increased following violent game play, and Bayesian analyzes confirmed that results are supportive of the null hypothesis. By contrast, VVG exposure increased stress, but only for girls. The impact of VVGs on teen hostility is minimal. However, players unfamiliar with such games may find them unpleasant. These results are put into the context of Uses and Gratifications Theory with suggestions for how medical professionals should address the issue of VVG play with concerned parents.

  18. Biosynthesis of vitamin C by yeast leads to increased stress resistance.

    Directory of Open Access Journals (Sweden)

    Paola Branduardi

    Full Text Available BACKGROUND: In industrial large scale bio-reactions micro-organisms are generally exposed to a variety of environmental stresses, which might be detrimental for growth and productivity. Reactive oxygen species (ROS play a key role among the common stress factors--directly--through incomplete reduction of O(2 during respiration, or indirectly--caused by other stressing factors. Vitamin C or L-ascorbic acid acts as a scavenger of ROS, thereby potentially protecting cells from harmful oxidative products. While most eukaryotes synthesize ascorbic acid, yeast cells produce erythro-ascorbic acid instead. The actual importance of this antioxidant substance for the yeast is still a subject of scientific debate. METHODOLOGY/PRINCIPAL FINDINGS: We set out to enable Saccharomyces cerevisiae cells to produce ascorbic acid intracellularly to protect the cells from detrimental effects of environmental stresses. We report for the first time the biosynthesis of L-ascorbic acid from D-glucose by metabolically engineered yeast cells. The amount of L-ascorbic acid produced leads to an improved robustness of the recombinant cells when they are subjected to stress conditions as often met during industrial fermentations. Not only resistance against oxidative agents as H(2O(2 is increased, but also the tolerance to low pH and weak organic acids at low pH is increased. CONCLUSIONS/SIGNIFICANCE: This platform provides a new tool whose commercial applications may have a substantial impact on bio-industrial production of Vitamin C. Furthermore, we propose S. cerevisiae cells endogenously producing vitamin C as a cellular model to study the genesis/protection of ROS as well as genotoxicity.

  19. Increased levels of thioredoxin in patients with abdominal aortic aneurysms (AAAs). A potential link of oxidative stress with AAA evolution

    DEFF Research Database (Denmark)

    Martinez-Pinna, R; Lindholt, Jes S.; Blanco-Colio, L M

    2010-01-01

    Oxidative stress is a main mechanism involved in vascular pathologies. Increased thioredoxin (TRX) levels have been observed in several oxidative stress-associated cardiovascular diseases. We aim to test the potential role of TRX as a biomarker of oxidative stress in abdominal aortic aneurysm (AAA)....

  20. Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage 0 COPD

    OpenAIRE

    Rytilä, Paula; Rehn, Tiina; Ilumets, Helen; Rouhos, Annamari; Sovijärvi, Anssi; Myllärniemi, Marjukka; Kinnula, Vuokko L

    2006-01-01

    Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress. The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD. Methods Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage...

  1. Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

    Science.gov (United States)

    Delis, Foteini; Thanos, Panayotis K; Rombola, Christina; Rosko, Lauren; Grandy, David; Wang, Gene-Jack; Volkow, Nora D

    2013-02-01

    Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  2. Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels

    International Nuclear Information System (INIS)

    Dutta, Anindita; Ray, Manas Ranjan; Banerjee, Anirban

    2012-01-01

    The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate > 100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM 10 and PM 2.5 , respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM 10 and PM 2.5 levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD. -- Highlights: ► Effect of chronic biomass smoke exposure on cardiovascular health was

  3. Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Anindita, E-mail: anidu14@gmail.com [College of Environmental Sciences and Engineering, Peking University, Beijing (China); Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700 026 (India); Ray, Manas Ranjan; Banerjee, Anirban [Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700 026 (India)

    2012-06-15

    The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate > 100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM{sub 10} and PM{sub 2.5}, respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM{sub 10} and PM{sub 2.5} levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD. -- Highlights: ► Effect of chronic biomass smoke exposure on

  4. Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat.

    Science.gov (United States)

    Linley, Stephanie B; Olucha-Bordonau, Francisco; Vertes, Robert P

    2017-01-01

    As is well recognized, serotonergic (5-HT) fibers distribute widely throughout the forebrain, including the amygdala. Although a few reports have examined the 5-HT innervation of select nuclei of the amygdala in the rat, no previous report has described overall 5-HT projections to the amygdala in the rat. Using immunostaining for the serotonin transporter, SERT, we describe the complete pattern of distribution of 5-HT fibers to the amygdala (proper) and to the extended amygdala in the rat. Based on its ontogenetic origins, the amygdala was subdivided into two major parts, pallial and subpallial components, with the pallial component further divided into superficial and deep nuclei (Olucha-Bordonau et al. 2015). SERT + fibers were shown to distributed moderately to densely to the deep and cortical pallial nuclei, but, by contrast, lightly to the subpallial nuclei. Specifically, 1) of the deep pallial nuclei, the lateral, basolateral, and basomedial nuclei contained a very dense concentration of 5-HT fibers; 2) of the cortical pallial nuclei, the anterior cortical and amygdala-cortical transition zone rostrally and the posteromedial and posterolateral nuclei caudally contained a moderate concentration of 5-HT fibers; and 3) of the subpallial nuclei, the anterior nuclei and the rostral part of the medial (Me) nuclei contained a moderate concentration of 5-HT fibers, whereas caudal regions of Me as well as the central nuclei and the intercalated nuclei contained a sparse/light concentration of 5-HT fibers. With regard to the extended amygdala (primarily the bed nucleus of stria terminalis; BST), on the whole, the BST contained moderate numbers of 5-HT fibers, spread fairly uniformly throughout BST. The findings are discussed with respect to a critical serotonergic influence on the amygdala, particularly on the basal complex, and on the extended amygdala in the control of states of fear and anxiety. J. Comp. Neurol. 525:116-139, 2017. © 2016 Wiley Periodicals, Inc.

  5. Gradually Increased Training Intensity Benefits Rehabilitation Outcome after Stroke by BDNF Upregulation and Stress Suppression

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2014-01-01

    Full Text Available Physical training is necessary for effective rehabilitation in the early poststroke period. Animal studies commonly use fixed training intensity throughout rehabilitation and without adapting it to the animals' recovered motor ability. This study investigated the correlation between training intensity and rehabilitation efficacy by using a focal ischemic stroke rat model. Eighty male Sprague-Dawley rats were induced with middle cerebral artery occlusion/reperfusion surgery. Sixty rats with successful stroke were then randomly assigned into four groups: control (CG, n=15, low intensity (LG, n=15, gradually increased intensity (GIG, n=15, and high intensity (HG, n=15. Behavioral tests were conducted daily to evaluate motor function recovery. Stress level and neural recovery were evaluated via plasma corticosterone and brain-derived neurotrophic factor (BDNF concentration, respectively. GIG rats significantly (P<0.05 recovered motor function and produced higher hippocampal BDNF (112.87 ± 25.18 ng/g. GIG and LG rats exhibited similar stress levels (540.63 ± 117.40 nM/L and 508.07 ± 161.30 nM/L, resp., which were significantly lower (P<0.05 than that (716.90 ± 156.48 nM/L of HG rats. Training with gradually increased intensity achieved better recovery with lower stress. Our observations indicate that a training protocol that includes gradually increasing training intensity should be considered in both animal and clinical studies for better stroke recovery.

  6. Gradually Increased Oxygen Administration Improved Oxygenation and Mitigated Oxidative Stress after Resuscitation from Severe Hemorrhagic Shock.

    Science.gov (United States)

    Luo, Xin; Yin, Yujing; You, Guoxing; Chen, Gan; Wang, Ying; Zhao, Jingxiang; Wang, Bo; Zhao, Lian; Zhou, Hong

    2015-11-01

    The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid-base status, oxygenation, and oxidative injury were observed and evaluated. Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor-α and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining. GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.

  7. Color It Real: A Program to Increase Condom Use and Reduce Substance Abuse and Perceived Stress

    Directory of Open Access Journals (Sweden)

    Tiffany Zellner

    2015-12-01

    Full Text Available Few interventions have targeted perceived stress as a co-occurring construct central to substance use and subsequent HIV/AIDS risk reduction among African American urban young adults. The Color It Real Program was a seven session, weekly administered age-specific and culturally-tailored intervention designed to provide substance abuse and HIV education and reduce perceived stress among African Americans ages 18 to 24 in Atlanta, GA. Effectiveness was assessed through a quasi-experimental study design that consisted of intervention (n = 122 and comparison (n = 70 groups completing a pre- and post-intervention survey. A series of Analysis of Variance (ANOVA tests were used to assess pre- to post-intervention changes between study groups. For intervention participants, perceived stress levels were significantly reduced by the end of the intervention (t(70 = 2.38, p = 0.020, condom use at last sexual encounter significantly increased (F = 4.43, p = 0.0360, intervention participants were significantly less likely to drink five or more alcoholic drinks in one sitting (F = 5.10, p = 0.0245, and to use clean needles when injecting the drug (F = 36.99, p = 0.0001. This study is among the first of its kind to incorporate stress management as an integral approach to HIV/SA prevention. The program has implications for the design of other community-based, holistic approaches to addressing substance use and risky behaviors for young adults.

  8. Stress system changes associated with marijuana dependence may increase craving for alcohol and cocaine

    Science.gov (United States)

    Fox, Helen C.; Tuit, Keri L.; Sinha, Rajita

    2013-01-01

    Objective To date, little research exists defining bio-behavioral adaptations associated with both marijuana abuse and risk of craving and relapse to other drugs of abuse during early abstinence. Method Fifty-nine treatment-seeking individuals dependent on alcohol and cocaine were recruited. Thirty of these individuals were also marijuana (MJ) dependent; 29 were not. Twenty-six socially drinking healthy controls were also recruited. All participants were exposed to three 5-min guided imagery conditions (stress, alcohol/cocaine cue and relaxing), presented randomly, one per day across three consecutive days. Measures of craving, anxiety, heart rate, blood pressure, plasma adrenocorticotrophic hormone and cortisol were collected at baseline and subsequent recovery time points. Results The MJ-dependent group showed increased basal anxiety ratings and cardiovascular output alongside enhanced alcohol craving and cocaine craving, and dampened cardiovascular response to stress and cue. They also demonstrated elevated cue-induced anxiety and stress-induced cortisol and adrenocorticotrophic hormone levels, which were not observed in the non-MJ-dependent group or controls. Cue-related alcohol craving and anxiety were both predictive of a shorter number of days to marijuana relapse following discharge from inpatient treatment. Conclusions Findings provide some support for drug cross-sensitization in terms of motivational processes associated with stress-related and cue-related craving and relapse. PMID:23280514

  9. Color It Real: A Program to Increase Condom Use and Reduce Substance Abuse and Perceived Stress.

    Science.gov (United States)

    Zellner, Tiffany; Trotter, Jennie; Lenoir, Shelia; Walston, Kelvin; Men-Na'a, L'dia; Henry-Akintobi, Tabia; Miller, Assia

    2015-12-22

    Few interventions have targeted perceived stress as a co-occurring construct central to substance use and subsequent HIV/AIDS risk reduction among African American urban young adults. The Color It Real Program was a seven session, weekly administered age-specific and culturally-tailored intervention designed to provide substance abuse and HIV education and reduce perceived stress among African Americans ages 18 to 24 in Atlanta, GA. Effectiveness was assessed through a quasi-experimental study design that consisted of intervention (n = 122) and comparison (n = 70) groups completing a pre- and post-intervention survey. A series of Analysis of Variance (ANOVA) tests were used to assess pre- to post-intervention changes between study groups. For intervention participants, perceived stress levels were significantly reduced by the end of the intervention (t(70) = 2.38, p = 0.020), condom use at last sexual encounter significantly increased (F = 4.43, p = 0.0360), intervention participants were significantly less likely to drink five or more alcoholic drinks in one sitting (F = 5.10, p = 0.0245), and to use clean needles when injecting the drug (F = 36.99, p = 0.0001). This study is among the first of its kind to incorporate stress management as an integral approach to HIV/SA prevention. The program has implications for the design of other community-based, holistic approaches to addressing substance use and risky behaviors for young adults.

  10. Positive Facial Affect – An fMRI Study on the Involvement of Insula and Amygdala

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    Pohl, Anna; Anders, Silke; Schulte-Rüther, Martin; Mathiak, Klaus; Kircher, Tilo

    2013-01-01

    Imitation of facial expressions engages the putative human mirror neuron system as well as the insula and the amygdala as part of the limbic system. The specific function of the latter two regions during emotional actions is still under debate. The current study investigated brain responses during imitation of positive in comparison to non-emotional facial expressions. Differences in brain activation of the amygdala and insula were additionally examined during observation and execution of facial expressions. Participants imitated, executed and observed happy and non-emotional facial expressions, as well as neutral faces. During imitation, higher right hemispheric activation emerged in the happy compared to the non-emotional condition in the right anterior insula and the right amygdala, in addition to the pre-supplementary motor area, middle temporal gyrus and the inferior frontal gyrus. Region-of-interest analyses revealed that the right insula was more strongly recruited by (i) imitation and execution than by observation of facial expressions, that (ii) the insula was significantly stronger activated by happy than by non-emotional facial expressions during observation and imitation and that (iii) the activation differences in the right amygdala between happy and non-emotional facial expressions were increased during imitation and execution, in comparison to sole observation. We suggest that the insula and the amygdala contribute specifically to the happy emotional connotation of the facial expressions depending on the task. The pattern of the insula activity might reflect increased bodily awareness during active execution compared to passive observation and during visual processing of the happy compared to non-emotional facial expressions. The activation specific for the happy facial expression of the amygdala during motor tasks, but not in the observation condition, might reflect increased autonomic activity or feedback from facial muscles to the amygdala. PMID

  11. Positive facial affect - an fMRI study on the involvement of insula and amygdala.

    Directory of Open Access Journals (Sweden)

    Anna Pohl

    Full Text Available Imitation of facial expressions engages the putative human mirror neuron system as well as the insula and the amygdala as part of the limbic system. The specific function of the latter two regions during emotional actions is still under debate. The current study investigated brain responses during imitation of positive in comparison to non-emotional facial expressions. Differences in brain activation of the amygdala and insula were additionally examined during observation and execution of facial expressions. Participants imitated, executed and observed happy and non-emotional facial expressions, as well as neutral faces. During imitation, higher right hemispheric activation emerged in the happy compared to the non-emotional condition in the right anterior insula and the right amygdala, in addition to the pre-supplementary motor area, middle temporal gyrus and the inferior frontal gyrus. Region-of-interest analyses revealed that the right insula was more strongly recruited by (i imitation and execution than by observation of facial expressions, that (ii the insula was significantly stronger activated by happy than by non-emotional facial expressions during observation and imitation and that (iii the activation differences in the right amygdala between happy and non-emotional facial expressions were increased during imitation and execution, in comparison to sole observation. We suggest that the insula and the amygdala contribute specifically to the happy emotional connotation of the facial expressions depending on the task. The pattern of the insula activity might reflect increased bodily awareness during active execution compared to passive observation and during visual processing of the happy compared to non-emotional facial expressions. The activation specific for the happy facial expression of the amygdala during motor tasks, but not in the observation condition, might reflect increased autonomic activity or feedback from facial muscles to the

  12. Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

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    Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

    2016-12-01

    Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses.

    Science.gov (United States)

    Klumpers, Floris; Kroes, Marijn C W; Baas, Johanna M P; Fernández, Guillén

    2017-10-04

    The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we used data from two independent functional magnetic resonance imaging studies [ n = 108 males and n = 70 (45 females)] to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from Sample 2 ( n = 48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses, respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST toward the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance toward acute threat responding and via that route predispose for affective disorder. SIGNIFICANCE STATEMENT Previously proposed differential contributions of the BNST and amygdala to fear and anxiety have been recently debated. Despite the significance of understanding their

  14. Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

    Science.gov (United States)

    Bijlsma, P B; van Raaij, M T; Dobbe, C J; Timmerman, A; Kiliaan, A J; Taminiau, J A; Groot, J A

    2001-05-01

    Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

  15. Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2015-02-01

    Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

  16. Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat