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Sample records for alters memory anxiety

  1. Anxiety promotes memory for mood-congruent faces but does not alter loss aversion

    PubMed Central

    Charpentier, Caroline J.; Hindocha, Chandni; Roiser, Jonathan P.; Robinson, Oliver J.

    2016-01-01

    Pathological anxiety is associated with disrupted cognitive processing, including working memory and decision-making. In healthy individuals, experimentally-induced state anxiety or high trait anxiety often results in the deployment of adaptive harm-avoidant behaviours. However, how these processes affect cognition is largely unknown. To investigate this question, we implemented a translational within-subjects anxiety induction, threat of shock, in healthy participants reporting a wide range of trait anxiety scores. Participants completed a gambling task, embedded within an emotional working memory task, with some blocks under unpredictable threat and others safe from shock. Relative to the safe condition, threat of shock improved recall of threat-congruent (fearful) face location, especially in highly trait anxious participants. This suggests that threat boosts working memory for mood-congruent stimuli in vulnerable individuals, mirroring memory biases in clinical anxiety. By contrast, Bayesian analysis indicated that gambling decisions were better explained by models that did not include threat or treat anxiety, suggesting that: (i) higher-level executive functions are robust to these anxiety manipulations; and (ii) decreased risk-taking may be specific to pathological anxiety. These findings provide insight into the complex interactions between trait anxiety, acute state anxiety and cognition, and may help understand the cognitive mechanisms underlying adaptive anxiety. PMID:27098489

  2. Anxiety promotes memory for mood-congruent faces but does not alter loss aversion.

    PubMed

    Charpentier, Caroline J; Hindocha, Chandni; Roiser, Jonathan P; Robinson, Oliver J

    2016-01-01

    Pathological anxiety is associated with disrupted cognitive processing, including working memory and decision-making. In healthy individuals, experimentally-induced state anxiety or high trait anxiety often results in the deployment of adaptive harm-avoidant behaviours. However, how these processes affect cognition is largely unknown. To investigate this question, we implemented a translational within-subjects anxiety induction, threat of shock, in healthy participants reporting a wide range of trait anxiety scores. Participants completed a gambling task, embedded within an emotional working memory task, with some blocks under unpredictable threat and others safe from shock. Relative to the safe condition, threat of shock improved recall of threat-congruent (fearful) face location, especially in highly trait anxious participants. This suggests that threat boosts working memory for mood-congruent stimuli in vulnerable individuals, mirroring memory biases in clinical anxiety. By contrast, Bayesian analysis indicated that gambling decisions were better explained by models that did not include threat or treat anxiety, suggesting that: (i) higher-level executive functions are robust to these anxiety manipulations; and (ii) decreased risk-taking may be specific to pathological anxiety. These findings provide insight into the complex interactions between trait anxiety, acute state anxiety and cognition, and may help understand the cognitive mechanisms underlying adaptive anxiety. PMID:27098489

  3. Alterations in spatial memory and anxiety in the MAM E17 rat model of hippocampal pathology in schizophrenia.

    PubMed

    Gastambide, Francois; Taylor, Amy M; Palmer, Clare; Svard, Heta; Karjalainen, Maija; Janhunen, Sanna K; Tricklebank, Mark; Bannerman, David M

    2015-11-01

    Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia. PMID:25633092

  4. Alterations in spatial memory and anxiety in the MAM E17 rat model of hippocampal pathology in schizophrenia.

    PubMed

    Gastambide, Francois; Taylor, Amy M; Palmer, Clare; Svard, Heta; Karjalainen, Maija; Janhunen, Sanna K; Tricklebank, Mark; Bannerman, David M

    2015-11-01

    Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia.

  5. Episodic Memories in Anxiety Disorders: Clinical Implications

    PubMed Central

    Zlomuzica, Armin; Dere, Dorothea; Machulska, Alla; Adolph, Dirk; Dere, Ekrem; Margraf, Jürgen

    2014-01-01

    The aim of this review is to summarize research on the emerging role of episodic memories in the context of anxiety disorders (AD). The available literature on explicit, autobiographical, and episodic memory function in AD including neuroimaging studies is critically discussed. We describe the methodological diversity of episodic memory research in AD and discuss the need for novel tests to measure episodic memory in a clinical setting. We argue that alterations in episodic memory functions might contribute to the etiology of AD. We further explain why future research on the interplay between episodic memory function and emotional disorders as well as its neuroanatomical foundations offers the promise to increase the effectiveness of modern psychological treatments. We conclude that one major task is to develop methods and training programs that might help patients suffering from AD to better understand, interpret, and possibly actively use their episodic memories in a way that would support therapeutic interventions and counteract the occurrence of symptoms. PMID:24795583

  6. How Misinformation Alters Memories.

    ERIC Educational Resources Information Center

    Wright, Daniel B.; Loftus, Elizabeth F.

    1998-01-01

    Notes that a multitude of studies have demonstrated that misleading postevent information affects people's memories. Contents that the fuzzy-trace theory is a positive step toward understanding the malleability of memory. Discusses fuzzy-trace theory in terms of three primary areas of study: altered response format, maximized misinformation…

  7. Autobiographical memory bias in social anxiety.

    PubMed

    Krans, Julie; de Bree, June; Bryant, Richard A

    2014-01-01

    In social anxiety the psychological self is closely related to the feared stimulus. Socially anxious individuals are, by definition, concerned about how the self is perceived and evaluated by others. As autobiographical memory is strongly related to views of the self it follows that biases in autobiographical memory play an important role in social anxiety. In the present study high (n = 19) and low (n = 29) socially anxious individuals were compared on autobiographical memory bias, current goals, and self-discrepancy. Individuals high in social anxiety showed a bias towards recalling more negative and more social anxiety-related autobiographical memories, reported more current goals related to overcoming social anxiety, and showed larger self-discrepancies. The pattern of results is largely in line with earlier research in individuals with PTSD and complicated grief. This suggests that the relation between autobiographical memory bias and the self is a potentially valuable trans-diagnostic factor.

  8. Emotions shape memory suppression in trait anxiety.

    PubMed

    Marzi, Tessa; Regina, Antonio; Righi, Stefania

    2014-01-01

    The question that motivated this study was to investigate the relation between trait anxiety, emotions and memory control. To this aim, memory suppression was explored in high and low trait anxiety individuals with the Think/No-think paradigm. After learning associations between neutral words and emotional scenes (negative, positive, and neutral), participants were shown a word and were requested either to think about the associated scene or to block it out from mind. Finally, in a test phase, participants were again shown each word and asked to recall the paired scene. The results show that memory control is influenced by high trait anxiety and emotions. Low trait anxiety individuals showed a memory suppression effect, whereas there was a lack of memory suppression in high trait anxious individuals, especially for emotionally negative scenes. Thus, we suggest that individuals with anxiety may have difficulty exerting cognitive control over memories with a negative valence. These findings provide evidence that memory suppression can be impaired by anxiety thus highlighting the crucial relation between cognitive control, emotions, and individual differences in regulating emotions.

  9. Effects of Mineralocorticoid Receptor Overexpression on Anxiety and Memory after Early Life Stress in Female Mice.

    PubMed

    Kanatsou, Sofia; Ter Horst, Judith P; Harris, Anjanette P; Seckl, Jonathan R; Krugers, Harmen J; Joëls, Marian

    2015-01-01

    Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice.

  10. Effects of Mineralocorticoid Receptor Overexpression on Anxiety and Memory after Early Life Stress in Female Mice

    PubMed Central

    Kanatsou, Sofia; Ter Horst, Judith P.; Harris, Anjanette P.; Seckl, Jonathan R.; Krugers, Harmen J.; Joëls, Marian

    2016-01-01

    Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice. PMID:26858618

  11. Influence of anxiety on memory performance in temporal lobe epilepsy

    PubMed Central

    Brown, Franklin C.; Westerveld, Michael; Langfitt, John T.; Hamberger, Marla; Hamid, Hamada; Shinnar, Shlomo; Sperling, Michael R.; Devinsky, Orrin; Barr, William; Tracy, Joseph; Masur, David; Bazil, Carl W.; Spencer, Susan S.

    2013-01-01

    This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 temporal lobe epilepsy patients from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was lower for those with high versus low level of anxiety, but was not found to be related to side of TLE. Verbal memory on the California Verbal Learning Test (CVLT) was significantly lower for left than right TLE patients with low anxiety, but equally impaired for those with high anxiety. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left TLE for those with low anxiety, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety level. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among TLE patients, regardless of anxiety level. PMID:24291525

  12. Influence of anxiety on memory performance in temporal lobe epilepsy.

    PubMed

    Brown, Franklin C; Westerveld, Michael; Langfitt, John T; Hamberger, Marla; Hamid, Hamada; Shinnar, Shlomo; Sperling, Michael R; Devinsky, Orrin; Barr, William; Tracy, Joseph; Masur, David; Bazil, Carl W; Spencer, Susan S

    2014-02-01

    This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 patients with temporal lobe epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was poorer for those with high versus low levels of anxiety but was not found to be related to the TLE side. The verbal memory score on the California Verbal Learning Test (CVLT) was significantly lower for patients with left-sided TLE than for patients with right-sided TLE with low anxiety levels but equally impaired for those with high anxiety levels. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left-sided TLE for those with low anxiety levels, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety levels. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety levels. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety levels. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among patients with TLE, regardless of anxiety levels.

  13. Influence of anxiety on memory performance in temporal lobe epilepsy.

    PubMed

    Brown, Franklin C; Westerveld, Michael; Langfitt, John T; Hamberger, Marla; Hamid, Hamada; Shinnar, Shlomo; Sperling, Michael R; Devinsky, Orrin; Barr, William; Tracy, Joseph; Masur, David; Bazil, Carl W; Spencer, Susan S

    2014-02-01

    This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 patients with temporal lobe epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was poorer for those with high versus low levels of anxiety but was not found to be related to the TLE side. The verbal memory score on the California Verbal Learning Test (CVLT) was significantly lower for patients with left-sided TLE than for patients with right-sided TLE with low anxiety levels but equally impaired for those with high anxiety levels. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left-sided TLE for those with low anxiety levels, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety levels. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety levels. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety levels. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among patients with TLE, regardless of anxiety levels. PMID:24291525

  14. Fluoxetine disrupts the integration of anxiety and aversive memories.

    PubMed

    Degroot, Aldemar; Nomikos, George G

    2005-02-01

    Anxiety disorders may result from an overexpression of aversive memories. Evidence suggests that the hippocampal cholinergic system could be the point of convergence of anxiety and memory. We propose that clinically effective anxiolytics may exert their effect by interfering with this integration mechanism. To assess anxiety and aversive memory, we used the shock-probe burying test. A reduction in anxiety in this test is indicated by decreased burying, whereas impaired cognition is reflected by an increased number of probe-contacts and/or reduced retention latency. Both an aversive stimulus and the memory of that stimulus significantly increased hippocampal acetylcholine (ACh) levels (Experiment 1). In fact, the memory of the event seemed to be more important than the event itself since the aversive memory induced a greater increase in hippocampal ACh. Injections (i.p.) of fluoxetine (Prozac) reduced burying behavior, while not affecting probe contacts or retention latency (Experiment 2). Although injections of fluoxetine did not affect basal hippocampal ACh efflux (Experiment 3), fluoxetine abolished the increase in ACh induced by the aversive stimulus and the memory of that stimulus (Experiment 4), emphasizing the significance of aversive memories in anxiety disorders. These actions may be mediated by a decrease in the event-related enhancement in cholinergic neurotransmission through M1 cholinergic receptors (Experiment 5). Therefore, anxiety disorders may stem from an unopposed formation of aversive memories and clinically effective anxiolytics hinder the association between emotional and cognitive processing. This reduces the emotional impact of aversive memories, thereby opposing consequent anxiety.

  15. Glucose enhancement of memory is modulated by trait anxiety in healthy adolescent males.

    PubMed

    Smith, Michael A; Hii, Hilary L; Foster, Jonathan K; van Eekelen, J A M

    2011-01-01

    Glucose administration is associated with memory enhancement in healthy young individuals under conditions of divided attention at encoding. While the specific neurocognitive mechanisms underlying this 'glucose memory facilitation effect' are currently uncertain, it is thought that individual differences in glucoregulatory efficiency may alter an individual's sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic-pituitary-adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14-17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic-pituitary-adrenal axis function did not appear to influence the glucose memory facilitation effect; however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety.

  16. Test Anxiety and Depression in Sentence Memory: Parallel Effects?

    ERIC Educational Resources Information Center

    Hedl, John J., Jr.

    Level of state test anxiety and depression were related to encoding strategy (imagery versus sematic instructions) in a study of sentence memory. Subjects were 80 female undergraduate students. Negative effects for test anxiety were found in both strategy conditions. Negative effects were found for depression when the semantic encoding strategy…

  17. High Trait Anxiety: A Challenge for Disrupting Fear Memory Reconsolidation

    PubMed Central

    Soeter, Marieke; Kindt, Merel

    2013-01-01

    Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation - n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice. PMID:24260096

  18. Impaired decision making and delayed memory are related with anxiety and depressive symptoms in acromegaly.

    PubMed

    Crespo, Iris; Santos, Alicia; Valassi, Elena; Pires, Patricia; Webb, Susan M; Resmini, Eugenia

    2015-12-01

    Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Moreover, the presence of affective disorders in these patients is common. Our aim was to evaluate memory and decision making in acromegalic patients and explore their relationship with affective disorders like anxiety and depressive symptoms. Thirty-one patients with acromegaly (mean age 49.5 ± 8.5 years, 14 females and 17 males) and thirty-one healthy controls participated in this study. The Iowa Gambling Task (IGT), Rey Auditory Verbal Learning Test, State-Trait Anxiety Inventory, and Beck Depression Inventory-II (BDI-II) were used to evaluate decision making, verbal memory, anxiety, and depressive symptoms, respectively. Acromegalic patients showed impairments in delayed verbal memory (p < 0.05) and more anxiety and depressive symptoms (p < 0.05) than controls. In the IGT, acromegalic patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (p < 0.05) and higher number of the riskier cards (p < 0.05). Moreover, multiple correlations between anxiety and depressive symptoms and performance in memory and decision making were found. Impaired delayed memory and decision making observed in acromegalic patients are related to anxiety and depressive symptoms. Providing emotional support to the patients could improve their cognitive function. A key clinical application of this research is the finding that depressive symptoms and anxiety are essentially modifiable factors.

  19. Treatment-related alteration of cortisol predicts change in neuropsychological function during acute treatment of late-life anxiety disorder

    PubMed Central

    Lenze, Eric J.; Dixon, David; Mantella, Rose C.; Dore, Peter M.; Andreescu, Carmen; Reynolds, Charles F.; Newcomer, John W.; Butters, Meryl A.

    2012-01-01

    Objective Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function. Methods We examined 60 adults aged 60 and older, who took part in a 12-week trial of escitalopram vs. placebo for Generalized Anxiety Disorder. All subjects had pre- and post-treatment assessments that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation. Results Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory, but no association with executive tasks (measures of working memory and set-shifting). Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes: memory improvement was seen with cortisol reduction among patients receiving escitalopram, but not among patients receiving placebo. Conclusion Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of Generalized Anxiety Disorder predicted changes in immediate and delayed memory. This finding suggests a novel treatment strategy in late-life anxiety disorders: targeting HPA axis dysfunction to improve memory. PMID:21681817

  20. Nicotine Modulation of Fear Memories and Anxiety: Implications for Learning and Anxiety Disorders

    PubMed Central

    Kutlu, Munir Gunes; Gould, Thomas J.

    2015-01-01

    Anxiety disorders are a group of crippling mental diseases affecting millions of Americans with a 30% lifetime prevalence and costs associated with healthcare of $42.3 billion. While anxiety disorders show high levels of co-morbidity with smoking (45.3% vs. 22.5% in healthy individuals), anxiety disorders are also more common among the smoking population (22% vs. 11.1% in the non-smoking population). Moreover, there is clear evidence that smoking modulates symptom severity in patients with anxiety disorders. In order to better understand this relationship, several animal paradigms are used to model several key symptoms of anxiety disorders; these include fear conditioning and measures of anxiety. Studies clearly demonstrate that nicotine mediates acquisition and extinction of fear as well as anxiety through the modulation of specific subtypes of nicotinic acetylcholine receptors (nAChRs) in brain regions involved in emotion processing such as the hippocampus. However, the direction of nicotine’s effects on these behaviors is determined by several factors that include the length of administration, hippocampus-dependency of the fear learning task, and source of anxiety (novelty-driven vs. social anxiety). Overall, the studies reviewed here suggest that nicotine alters behaviors related to fear and anxiety and that nicotine contributes to the development, maintenance, and reoccurrence of anxiety disorders. PMID:26231942

  1. The Contribution of Memory and Anxiety to the Math Performance of College Students with Learning Disabilities

    ERIC Educational Resources Information Center

    Prevatt, Frances; Welles, Theresa L.; Li, Huijun; Proctor, Briley

    2010-01-01

    The impact of memory and anxiety on math performance was analyzed in a sample of 115 college undergraduates, all of whom had a diagnosed learning disability. The direct effects of memory and anxiety on math performance were first examined, followed by an examination of whether anxiety moderates the relationship between memory and math. Both memory…

  2. Test Anxiety and Effort-Toward-Comprehension in Sentence Memory.

    ERIC Educational Resources Information Center

    Hedl, John J., Jr.; Bartlett, James

    Using an effort toward comprehension paradigm developed by P. M. Auble, J. J. Franks, and S. A. Soraci, Jr. (1979), the worry component of state test anxiety was related to long-term memory for sentence encoding conditions that involved comprehension, but low effort (embedded-cue) and comprehension-high effort (post-cue). A noncomprehension…

  3. Anxiety, Methylphenidate Response, and Working Memory in Children with ADHD

    ERIC Educational Resources Information Center

    Bedard, Anne-Claude; Tannock, Rosemary

    2008-01-01

    Objective: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in children with ADHD and determine whether MPH produces differential effects on WM in children with comorbid anxiety (ANX). Method: Participants were a clinical sample of 130 children with ADHD, aged 6 to 12 years old (32% comorbid ANX). Each child…

  4. Worrying Thoughts Limit Working Memory Capacity in Math Anxiety

    PubMed Central

    Shi, Zhan; Liu, Peiru

    2016-01-01

    Sixty-one high-math-anxious persons and sixty-one low-math-anxious persons completed a modified working memory capacity task, designed to measure working memory capacity under a dysfunctional math-related context and working memory capacity under a valence-neutral context. Participants were required to perform simple tasks with emotionally benign material (i.e., lists of letters) over short intervals while simultaneously reading and making judgments about sentences describing dysfunctional math-related thoughts or sentences describing emotionally-neutral facts about the world. Working memory capacity for letters under the dysfunctional math-related context, relative to working memory capacity performance under the valence-neutral context, was poorer overall in the high-math-anxious group compared with the low-math-anxious group. The findings show a particular difficulty employing working memory in math-related contexts in high-math-anxious participants. Theories that can provide reasonable interpretations for these findings and interventions that can reduce anxiety-induced worrying intrusive thoughts or improve working memory capacity for math anxiety are discussed. PMID:27788235

  5. The endocannabinoid system in anxiety, fear memory and habituation

    PubMed Central

    Ruehle, S; Rey, A Aparisi; Remmers, F

    2012-01-01

    Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations. This dual functionality, together with the plasticity of CB1 receptor expression, particularly on GABAergic neurons, as induced by stressful and rewarding experiences, gives the ECS a unique regulatory capacity for maintaining emotional homeostasis. However, the promiscuity of the endogenous ligands of the CB1 receptor complicates the interpretation of experimental data concerning ECS and anxiety. In fear memory paradigms, the ECS is mostly involved in the two opposing processes of reconsolidation and extinction of the fear memory. Whereas ECS activation deteriorates reconsolidation, proper extinction depends on intact CB1 receptor signalling. Thus, both for anxiety and fear memory processing, endocannabinoid signalling may ensure an appropriate reaction to stressful events. Therefore, the ECS can be considered as a regulatory buffer system for emotional responses. PMID:21768162

  6. Memory bias for threatening information in anxiety and anxiety disorders: a meta-analytic review.

    PubMed

    Mitte, Kristin

    2008-11-01

    Although some theories suggest that anxious individuals selectively remember threatening stimuli, findings remain contradictory despite a considerable amount of research. A quantitative integration of 165 studies with 9,046 participants (clinical and nonclinical samples) examined whether a memory bias exists and which moderator variables influence its magnitude. Implicit memory bias was investigated in lexical decision/stimulus identification and word-stem completion paradigms; explicit memory bias was investigated in recognition and recall paradigms. Overall, effect sizes showed no significant impact of anxiety on implicit memory and recognition. Analyses indicated a memory bias for recall, whose magnitude depended on experimental study procedures like the encoding procedure or retention interval. Anxiety influenced recollection of previous experiences; anxious individuals favored threat-related information. Across all paradigms, clinical status was not significantly linked to effect sizes, indicating no qualitative difference in information processing between anxiety patients and high-anxious persons. The large discrepancy between study effects in recall and recognition indicates that future research is needed to identify moderator variables for avoidant and preferred remembering.

  7. The Relationship between Anxiety-Stability, Working Memory and Cognitive Style

    ERIC Educational Resources Information Center

    Grimley, Michael; Dahraei, Hassan; Riding, Richard J.

    2008-01-01

    While prior research indicates that relationships exist between anxiety-stability and working memory, and cognitive style and anxiety-stability, they have not been considered together. The aim of this study was to consider how anxiety-stability is related to working memory, gender and style in interaction. The sample consisted of 179…

  8. Effects of Anxiety on Memory Storage and Updating in Young Children

    ERIC Educational Resources Information Center

    Visu-Petra, Laura; Cheie, Lavinia; Benga, Oana; Alloway, Tracy Packiam

    2011-01-01

    The relationship between trait anxiety and memory functioning in young children was investigated. Two studies were conducted, using tasks tapping verbal and visual-spatial short-term memory (Study 1) and working memory (Study 2) in preschoolers. On the verbal storage tasks, there was a detrimental effect of anxiety on processing efficiency…

  9. ERP measures of math anxiety: how math anxiety affects working memory and mental calculation tasks?

    PubMed

    Klados, Manousos A; Simos, Panagiotis; Micheloyannis, Sifis; Margulies, Daniel; Bamidis, Panagiotis D

    2015-01-01

    There have been several attempts to account for the impact of Mathematical Anxiety (MA) on brain activity with variable results. The present study examines the effects of MA on ERP amplitude during performance of simple arithmetic calculations and working memory tasks. Data were obtained from 32 university students as they solved four types of arithmetic problems (one- and two-digit addition and multiplication) and a working memory task comprised of three levels of difficulty (1, 2, and 3-back task). Compared to the Low-MA group, High-MA individuals demonstrated reduced ERP amplitude at frontocentral (between 180-320 ms) and centroparietal locations (between 380-420 ms). These effects were independent of task difficulty/complexity, individual performance, and general state/trait anxiety levels. Results support the hypothesis that higher levels of self-reported MA are associated with lower cortical activation during the early stages of the processing of numeric stimuli in the context of cognitive tasks.

  10. Effects of bilobalide on anxiety, spatial learning, memory and levels of hippocampal glucocorticoid receptors in male Kunming mice.

    PubMed

    Ma, Leige; Wang, Shiyan; Tai, Fadao; Yuan, Gang; Wu, Ruiyong; Liu, Xiao; Wei, Bin; Yang, Xiangping

    2012-12-15

    With various constituents in ginkgo biloba extract, the detailed internal mechanism underlying a reduction in anxiety and improvements to learning and memory from GBE is not well understood. The present study investigated whether bilobalide, an important constituent in GBE, could affect anxiety, spatial learning and memory in male mice and whether hippocampal glucocorticoid receptor expression is associated with alteration in these behaviors. Mice were treated orally either with sesame seed oil or one of three dosages of bilobalide (2.5, 5.0 and 10.0 mg/kg) daily until testing. A series of behavioral tests showed that repeated bilobalide treatment decreased levels of anxiety-like behavior and increased locomotor activity in open field and elevated plus maze tests. Treatment with bilobalide also shortened the time taken to find the platform in a Morris water-maze test. Mice exposed to bilobalide showed higher and dose-dependent levels of glucocorticoid receptor expression in the hippocampus. These results suggest that bilobalide reduces anxiety levels and enhances spatial learning and memory, possibly through an increase in hippocampal glucocorticoid receptor expression. This finding sheds light on the mechanisms underlying the effect of ginkgo biloba extract on behavior and also provides an important candidate drug in treatment of anxiety, depression, hypomnesia and amnesia.

  11. Influence of chronic moderate sleep restriction and exercise training on anxiety, spatial memory, and associated neurobiological measures in mice.

    PubMed

    Zielinski, Mark R; Davis, J Mark; Fadel, James R; Youngstedt, Shawn D

    2013-08-01

    Sleep deprivation can have deleterious effects on cognitive function and mental health. Moderate exercise training has myriad beneficial effects on cognition and mental health. However, physiological and behavioral effects of chronic moderate sleep restriction and its interaction with common activities, such as moderate exercise training, have received little investigation. The aims of this study were to examine the effects of chronic moderate sleep restriction and moderate exercise training on anxiety-related behavior, spatial memory, and neurobiological correlates in mice. Male mice were randomized to one of four 11-week treatments in a 2 [sleep restriction (∼4h loss/day) vs. ad libitum sleep] × 2 [exercise (1h/day/6 d/wk) vs. sedentary activity] experimental design. Anxiety-related behavior was assessed with the elevated-plus maze, and spatial learning and memory were assessed with the Morris water maze. Chronic moderate sleep restriction did not alter anxiety-related behavior, but exercise training significantly attenuated anxiety-related behavior. Spatial learning and recall, hippocampal cell activity (i.e., number of c-Fos positive cells), and brain derived neurotrophic factor were significantly lower after chronic moderate sleep restriction, but higher after exercise training. Further, the benefit of exercise training for some memory variables was evident under normal sleep, but not chronic moderate sleep restriction conditions. These data indicate clear detrimental effects of chronic moderate sleep restriction on spatial memory and that the benefits of exercise training were impaired after chronic moderate sleep restriction.

  12. Fmr1 knockout mice show reduced anxiety and alterations in neurogenesis that are specific to the ventral dentate gyrus.

    PubMed

    Eadie, B D; Zhang, W N; Boehme, F; Gil-Mohapel, J; Kainer, L; Simpson, J M; Christie, B R

    2009-11-01

    Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the selective loss of the expression of the Fmr1 gene. Key symptoms in FXS include intellectual impairment and abnormal anxiety-related behaviors. Fmr1 knockout (KO) mice exhibited reduced anxiety on two behavioral tests as well as a blunted corticosterone response to acute stress. Spatial learning and memory was not impaired when tested with both the classic Morris water and Plus-shaped mazes. Adult hippocampal neurogenesis has been associated with spatial learning and memory and emotions such as anxiety and depression. The process of neurogenesis appears abnormal in young adult Fmr1 KO mice, with significantly fewer bromodeoxyuridine-positive cells surviving for at least 4 weeks in the ventral subregion of the dentate gyrus (DG), a hippocampal subregion more closely associated with emotion than the dorsal DG. Within this smaller pool of surviving cells, we observed a concomitant increase in the proportion of surviving cells that acquire a neuronal phenotype. We did not observe a clear difference in cell proliferation using both endogenous and exogenous markers. This work indicates that loss of Fmr1 expression can alter anxiety-related behaviors in mice as well as produce region-specific alterations in hippocampal adult neurogenesis.

  13. Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression.

    PubMed

    Darcet, Flavie; Mendez-David, Indira; Tritschler, Laurent; Gardier, Alain M; Guilloux, Jean-Philippe; David, Denis J

    2014-01-01

    Cognitive disturbances are often reported as serious incapacitating symptoms by patients suffering from major depressive disorders (MDDs). Such deficits have been observed in various animal models based on environmental stress. Here, we performed a complete characterization of cognitive functions in a neuroendocrine mouse model of depression based on a chronic (4 weeks) corticosterone administration (CORT). Cognitive performances were assessed using behavioral tests measuring episodic (novel object recognition test, NORT), associative (one-trial contextual fear conditioning, CFC), and visuo-spatial (Morris water maze, MWM; Barnes maze, BM) learning/memory. Altered emotional phenotype after chronic corticosterone treatment was confirmed in mice using tests predictive of anxiety or depression-related behaviors. In the NORT, CORT-treated mice showed a decrease in time exploring the novel object during the test session and a lower discrimination index compared to control mice, characteristic of recognition memory impairment. Associative memory was also impaired, as observed with a decrease in freezing duration in CORT-treated mice in the CFC, thus pointing out the cognitive alterations in this model. In the MWM and in the BM, spatial learning performance but also short-term spatial memory were altered in CORT-treated mice. In the MWM, unlike control animals, CORT-treated animals failed to learn a new location during the reversal phase, suggesting a loss of cognitive flexibility. Finally, in the BM, the lack of preference for the target quadrant during the recall probe trial in animals receiving corticosterone regimen demonstrates that long-term retention was also affected in this paradigm. Taken together, our results highlight that CORT-induced anxio-depressive-like phenotype is associated with a cognitive deficit affecting all aspects of memory tested.

  14. ERP measures of math anxiety: how math anxiety affects working memory and mental calculation tasks?

    PubMed Central

    Klados, Manousos A.; Simos, Panagiotis; Micheloyannis, Sifis; Margulies, Daniel; Bamidis, Panagiotis D.

    2015-01-01

    There have been several attempts to account for the impact of Mathematical Anxiety (MA) on brain activity with variable results. The present study examines the effects of MA on ERP amplitude during performance of simple arithmetic calculations and working memory tasks. Data were obtained from 32 university students as they solved four types of arithmetic problems (one- and two-digit addition and multiplication) and a working memory task comprised of three levels of difficulty (1, 2, and 3-back task). Compared to the Low-MA group, High-MA individuals demonstrated reduced ERP amplitude at frontocentral (between 180–320 ms) and centroparietal locations (between 380–420 ms). These effects were independent of task difficulty/complexity, individual performance, and general state/trait anxiety levels. Results support the hypothesis that higher levels of self-reported MA are associated with lower cortical activation during the early stages of the processing of numeric stimuli in the context of cognitive tasks. PMID:26578912

  15. ERP measures of math anxiety: how math anxiety affects working memory and mental calculation tasks?

    PubMed

    Klados, Manousos A; Simos, Panagiotis; Micheloyannis, Sifis; Margulies, Daniel; Bamidis, Panagiotis D

    2015-01-01

    There have been several attempts to account for the impact of Mathematical Anxiety (MA) on brain activity with variable results. The present study examines the effects of MA on ERP amplitude during performance of simple arithmetic calculations and working memory tasks. Data were obtained from 32 university students as they solved four types of arithmetic problems (one- and two-digit addition and multiplication) and a working memory task comprised of three levels of difficulty (1, 2, and 3-back task). Compared to the Low-MA group, High-MA individuals demonstrated reduced ERP amplitude at frontocentral (between 180-320 ms) and centroparietal locations (between 380-420 ms). These effects were independent of task difficulty/complexity, individual performance, and general state/trait anxiety levels. Results support the hypothesis that higher levels of self-reported MA are associated with lower cortical activation during the early stages of the processing of numeric stimuli in the context of cognitive tasks. PMID:26578912

  16. Prenatal Stress Alters Hippocampal Neuroglia and Increases Anxiety in Childhood.

    PubMed

    Bennett, Greer A; Palliser, Hannah K; Shaw, Julia C; Walker, David; Hirst, Jonathan J

    2015-01-01

    Prenatal stress has been associated with detrimental outcomes of pregnancy, including altered brain development leading to behavioural pathologies. The neurosteroid allopregnanolone has been implicated in mediating some of these adverse outcomes following prenatal stress due to its potent inhibitory and anxiolytic effects on the brain. The aims of the current study were to characterise key markers for brain development as well as behavioural parameters, adrenocortical responses to handling and possible neurosteroid influences towards outcomes in guinea pig offspring in childhood. Pregnant guinea pig dams were exposed to strobe light for 2 h (9-11 a.m.) on gestational days 50, 55, 60, and 65 and were left to deliver spontaneously at term and care for their litter. Behavioural testing (open-field test, object exploration test) of the offspring was performed at postnatal day 18 (with salivary cortisol and DHEA measured), and brains were collected at post-mortem on day 21. Markers of brain development myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry, and the neurosteroid allopregnanolone and its rate-limiting enzymes 5α-reductase types 1 and 2 (5αR1/2) were measured in neonatal brains by radioimmunoassay, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot, respectively. Brain-derived neurotrophic factor protein was measured as a marker of synaptic plasticity, and GABAA receptor subunit expression was also assessed using RT-PCR. Neonates born from mothers stressed during late pregnancy showed a reduction in both MBP (p < 0.01) and GFAP (p < 0.05) expression in the CA1 region of the hippocampus at 21 days of age. Pups of prenatally stressed pregnancies also showed higher levels of anxiety and neophobic behaviours at the equivalent of childhood (p < 0.05). There were no significant changes observed in allopregnanolone levels, 5αR1/2 expression, or GABAA receptor subunit expression in

  17. Mathematics anxiety and working memory: support for the existence of a deficient inhibition mechanism.

    PubMed

    Hopko, D R; Ashcraft, M H; Gute, J; Ruggiero, K J; Lewis, C

    1998-01-01

    A current theory of anxiety effects in cognition claims that anxiety disrupts normal processing within the working memory system. We examined this theory in the context of a reading task, for participants who were high or low in assessed mathematics anxiety. The task was designed to measure the ability to inhibit attention to distracting information and the effects of this ability on explicit memory performance. The results suggested that math-anxious individuals have a deficient inhibition mechanism whereby working memory resources are consumed by task-irrelevant distracters. A consequence of this deficiency was that explicit memory performance was poorer for high-anxious individuals. Based on these results, the recommendation is made that Eysenck and Calvo's (1992) processing efficiency theory be integrated with Connelly, Hasher, and Zack's (1991) inhibition theory to portray more comprehensively the relation between anxiety and performance. PMID:9699118

  18. The Role of Anxiety and Working Memory in Gender Differences in Mathematics

    ERIC Educational Resources Information Center

    Ganley, Colleen M.; Vasilyeva, Marina

    2014-01-01

    This research examined a potential mechanism underlying gender differences in math performance by testing a mediation model in which women's higher anxiety taxes their working memory resources, leading to underperformance on a mathematics test. Participants for the 2 studies were college students (N = 87, N = 118) who completed an anxiety measure,…

  19. Associations among Selective Attention, Memory Bias, Cognitive Errors and Symptoms of Anxiety in Youth

    ERIC Educational Resources Information Center

    Watts, Sarah E.; Weems, Carl F.

    2006-01-01

    The purpose of this study was to examine the linkages among selective attention, memory bias, cognitive errors, and anxiety problems by testing a model of the interrelations among these cognitive variables and childhood anxiety disorder symptoms. A community sample of 81 youth (38 females and 43 males) aged 9-17 years and their parents completed…

  20. Neural activity during self-referential working memory and the underlying role of the amygdala in social anxiety disorder.

    PubMed

    Yoon, Hyung-Jun; Kim, Jin Seong; Shin, Yu-Bin; Choi, Soo-Hee; Lee, Seung-Koo; Kim, Jae-Jin

    2016-08-01

    Self-referential processing, theory of mind, and working memory are distorted in social anxiety disorder (SAD). This study aimed to investigate characteristics of altered self-referential working memory processing and resting-state functional connectivity in patients with SAD. Twenty patients and 20 healthy controls underwent functional magnetic resonance imaging at resting-state and while performing a working memory task containing faces with self-referential positive or negative comments and three memory phases (encoding, maintenance, and retrieval). Task-related results were compared between groups and tested for correlations. Resting-state connectivity between amygdala subregions and regions showing a task-related difference was also compared between groups. Patients compared to controls showed augmented memory for the negative comments, hyperactivation of the dorsomedial prefrontal cortex and temporo-parietal junction during encoding, and hypoactivation of the dorsolateral prefrontal cortex and insula during retrieval. At resting-state, increased connectivity of amygdala subregions with multiple task-related regions was found in patients. These findings suggest that the encoding process in SAD is accompanied by altered involvement of self-referential processing and theory of mind, whereas the retrieval process reflects impaired cognitive control. These memory-related processing may be affected by predisposing resting-state hyperconnectivity with the amygdala, and may underlie a hypersensitivity to negative comments and post-event reflection in SAD. PMID:27260987

  1. High intelligence prevents the negative impact of anxiety on working memory.

    PubMed

    Chuderski, Adam

    2015-01-01

    Using a large sample and the confirmatory factor analysis, the study investigated the relationships between anxiety, working memory (WM) and (fluid) intelligence. The study showed that the negative impact of anxiety on WM functioning diminishes with increasing intelligence, and that anxiety can significantly affect WM only in people below average intelligence. This effect could not be fully explained by the sheer differences in WM capacity (WMC), suggesting the importance of higher-level cognition in coping with anxiety. Although intelligence moderated the impact of anxiety on WM, it was only weakly related to anxiety. In contrast to previous studies, anxiety explained the substantial amount of WMC variance (17.8%) in less intelligent participants, but none of the variance in more intelligent ones. These results can be explained in terms of either increased motivation of intelligent but anxious people to cope with a WM task, or their ability to compensate decrements in WM.

  2. Stereotype Threat Alters the Subjective Experience of Memory.

    PubMed

    Mazerolle, Marie; Régner, Isabelle; Rigalleau, François; Huguet, Pascal

    2015-01-01

    There is now evidence that negative age-related stereotypes about memory reduce older adults' memory performance, and inflate age differences in this domain. Here, we examine whether stereotype threat may also influence the basic feeling that one is more or less able to remember. Using the Remember/Know paradigm, we demonstrated that stereotype threat conducted older adults to a greater feeling of familiarity with events, while failing to retrieve any contextual detail. This finding indicates that stereotype threat alters older adults' subjective experience of memory, and strengthens our understanding of the mechanisms underlying stereotype threat effects. PMID:27120561

  3. Stereotype Threat Alters the Subjective Experience of Memory.

    PubMed

    Mazerolle, Marie; Régner, Isabelle; Rigalleau, François; Huguet, Pascal

    2015-01-01

    There is now evidence that negative age-related stereotypes about memory reduce older adults' memory performance, and inflate age differences in this domain. Here, we examine whether stereotype threat may also influence the basic feeling that one is more or less able to remember. Using the Remember/Know paradigm, we demonstrated that stereotype threat conducted older adults to a greater feeling of familiarity with events, while failing to retrieve any contextual detail. This finding indicates that stereotype threat alters older adults' subjective experience of memory, and strengthens our understanding of the mechanisms underlying stereotype threat effects.

  4. Memory generalization is selectively altered in the psychosis dimension.

    PubMed

    Ivleva, Elena I; Shohamy, Daphna; Mihalakos, Perry; Morris, David W; Carmody, Thomas; Tamminga, Carol A

    2012-06-01

    Global deficits in declarative memory are commonly reported in individuals with schizophrenia and psychotic bipolar disorder, and in their biological relatives. However, it remains unclear whether there are specific components within the global declarative memory dysfunction that are unique to schizophrenia and bipolar disorder, or whether these impairments overlap the two psychoses. This study sought to characterize differential components of learning and memory in individuals within the psychosis dimension: probands with schizophrenia (SZP, n=33), probands with psychotic bipolar I disorder (BDP, n=20), and biological relatives of SZP (SZR, n=21), contrasted with healthy controls (HC, n=26). A computerized cognitive paradigm, the Acquired Equivalence test, with probes for associative learning, memory for learned associations, and memory generalization was administered, along with standardized neuropsychological measures of declarative memory. All study groups were able to learn and remember the associations, although SZP were slower than HC in the initial learning stages. Both SZP (significantly) and BDP (at a trend level) showed altered memory generalization compared to HC (SZP vs. HC, p=.038, d=.8; BDP vs. HC, p=.069, d=.95). SZR showed memory generalization intermediate between SZP and HC, although their performance did not differ significantly from either group. These findings indicate that probands with schizophrenia and bipolar psychoses have similar alteration in the ability to flexibly generalize learned knowledge when probed with novel stimuli, despite overall sufficient associative learning and memory for what they learned. These results suggest that the two disorders present a clinical continuum with overlapping hippocampus-mediated memory generalization dysfunction underlying the psychosis phenotype.

  5. Faces in the dark: interactive effects of darkness and anxiety on the memory for threatening faces.

    PubMed

    Nakashima, Satoshi F; Morimoto, Yuko; Takano, Yuji; Yoshikawa, Sakiko; Hugenberg, Kurt

    2014-01-01

    In the current research, we extend past work on the effects of ambient darkness and threat to the domain of memory for expressive faces. In one study, we examined the effects of ambient darkness and individual differences in state anxiety on memory of unfamiliar expressive faces. Here, participants were seated in either a dark or light room and encoded a set of unfamiliar faces with angry, happy, and neutral facial expressions. A subsequent recognition task revealed an interactive effect of ambient darkness, anxiety, and target expression. Highly anxious participants in ambient darkness had worse memory for angry faces than did low-anxiety participants. On the other hand, the recognition performance for happy faces was affected neither by the darkness nor state anxiety. The results suggest not only that ambient darkness has its strongest effect on anxious perceivers, but also that person × situation effects should be considered in face recognition research.

  6. Altered Human Memory Modification in the Presence of Normal Consolidation.

    PubMed

    Censor, Nitzan; Buch, Ethan R; Nader, Karim; Cohen, Leonardo G

    2016-09-01

    Following initial learning, the memory is stabilized by consolidation mechanisms, and subsequent modification of memory strength occurs via reconsolidation. Yet, it is not clear whether consolidation and memory modification are the same or different systems-level processes. Here, we report disrupted memory modification in the presence of normal consolidation of human motor memories, which relate to differences in lesioned brain structure after stroke. Furthermore, this behavioral dissociation was associated with macrostructural network architecture revealed by a graph-theoretical approach, and with white-matter microstructural integrity measured by diffusion-weighted MRI. Altered macrostructural network architecture and microstructural integrity of white-matter underlying critical nodes of the related network predicted disrupted memory modification. To the best of our knowledge, this provides the first evidence of mechanistic differences between consolidation, and subsequent memory modification through reconsolidation, in human procedural learning. These findings enable better understanding of these memory processes, which may guide interventional strategies to enhance brain function and resulting behavior. PMID:26271110

  7. The effects of imperatorin on anxiety and memory-related behavior in male Swiss mice.

    PubMed

    Budzynska, Barbara; Kruk-Slomka, Marta; Skalicka-Wozniak, Krystyna; Biala, Grazyna; Glowniak, Kazimierz

    2012-08-01

    The purpose of the reported experiments was to examine the effects of imperatorin [9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one], a bioactive furanocoumarin isolated from the fruits of Angelica archangelica (Angelica officinalis) on anxiety and memory-related behaviors of mice. Male Swiss mice were tested for anxiety and cognition, in the elevated plus maze test (EPM), using two different procedures. In the present experiments, imperatorin was administered acutely (at the doses of 5, 10, 20, 30, and 50 mg/kg); injections were made 15, 30, and 60 min before test (anxiety); 30 min before the first trial (memory acquisition); or immediately after the first trial (memory consolidation), as well as subchronically, twice a day for 6 days. On the seventh day, the mice were injected once with imperatorin (10 and 20 mg/kg, i.p.) 30 min before the test (anxiety) and 30 min before the first trial (memory acquisition), or immediately after the first trial (memory consolidation). We observed that imperatorin when administered acutely and repeatedly, at the doses of 10 and 20 mg/kg, exerted an anxiolytic effect on mice tested 30 min after the injection measured in the EPM test. By contrast, no such effect was observed after the acute administration of imperatorin at the doses of 5, 30 and 50 mg/kg. Moreover, other observations carried out 15 and 60 min after a single injection of the drug did not reveal any effect of imperatorin on anxiety behavior in the EPM test. Furthermore, acute and repeated administration of imperatorin (10 and 20 mg/kg) improved different stages of memory processes (both acquisition and consolidation) in a modified EPM test (mEPM). The results of our research suggest imperatorin to be an interesting therapeutical option in disorders with high anxiety levels and memory impairment. PMID:22686497

  8. The effects of competitive anxiety on memory span and rebound shooting tasks in basketball players.

    PubMed

    Parfitt, G; Hardy, L

    1993-12-01

    Two theoretical models were used to investigate aspects of basketball performance: Eysenck's (1979, 1984) compensatory arousal model and Humphreys and Revelle's (1984) twin resources model. Cognitive and somatic anxiety were manipulated using a 'time to event' paradigm. The aspects of performance were a short-term memory task (letter span) and a low memory demand, motoric-sustained information transfer task (rebound shooting). Hypotheses based on the different models were formulated and subsequently tested using analysis of variance and polynomial regression analysis. The results indicated significant (P < 0.01) linear relationships with negative slopes between cognitive anxiety and letter span, and between somatic anxiety and letter span; while significant (P < 0.01) linear relationships with positive slopes were recorded between cognitive anxiety and rebound shooting, and between somatic anxiety and rebound shooting. The analysis of variance results were in agreement with a positive effect (P < 0.05) for cognitive anxiety upon rebound shooting, and a negative effect which approached significance (P < 0.07) for somatic anxiety upon letter span. The results were interpreted as offering partial support for Eysenck's (1979) theoretical model, although further examination of multidimensional anxiety effects via the two models is warranted.

  9. The Relation between Test Anxiety and Need for Memory Support in Problem Solving. Revised Research Memorandum No. 11.

    ERIC Educational Resources Information Center

    Sieber, Joan E.; Kameya, Lawrence I.

    Forty fifth and sixth graders, matched on sex and measures of test anxiety, defensiveness, and IQ, were divided into two groups, each of which solved Porteus maze tasks and a marble puzzle, with and without memory support, respectively. An anxiety-by-memory support interaction occurred in the number of errors made prior to solving the marble…

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

    PubMed Central

    Sarro, Emma C; Sullivan, Regina M; Barr, Gordon

    2014-01-01

    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, PTSD 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. PMID:24240029

  11. Early deprivation reduced anxiety and enhanced memory in adult male rats.

    PubMed

    Zhang, Xuliang; Wang, Bo; Jin, Jing; An, Shuming; Zeng, Qingwen; Duan, Yanhong; Yang, Liguo; Ma, Jing; Cao, Xiaohua

    2014-09-01

    The effects of early deprivation (ED, which involves both dam and littermate deprivation) on anxiety and memory are less investigated in comparison with maternal separation (MS), and it is not yet clear how ED affects long-term potentiation (LTP) in the hippocampal Schaffer collateral pathway. By using a series of behavioral tests, enzyme-linked immunosorbent assay and field potential recording, we explored the effect of pre-weaning daily 3-h ED on anxiety, memory and potential mechanisms in adult male rats. Compared with control, ED rats spent longer time in open arms of elevated plus maze and in light compartment of light-dark transition box. Consistently, stress-induced blood plasma corticosterone level was also lower in ED rats. Moreover, ED rats showed better performance in social recognition and Morris water maze test. In accordance with results in memory tests, the threshold of LTP induction in hippocampal CA3-CA1 pathway of ED rats was also reduced. Our results indicate ED reduced anxiety, but enhanced social recognition and spatial reference memory. We suggest the diminished hypothalamic-pituitary-adrenal axis response and facilitated hippocampal LTP may contribute to the anxiety-reducing and memory-enhancing effects of ED, respectively.

  12. The Structural Connectivity Pattern of the Default Mode Network and Its Association with Memory and Anxiety

    PubMed Central

    Tao, Yan; Liu, Bing; Zhang, Xiaolong; Li, Jin; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2015-01-01

    The default mode network (DMN) is one of the most widely studied resting state functional networks. The structural basis for the DMN is of particular interest and has been studied by several researchers using diffusion tensor imaging (DTI). Most of these previous studies focused on a few regions or white matter tracts of the DMN so that the global structural connectivity pattern and network properties of the DMN remain unclear. Moreover, evidences indicate that the DMN is involved in both memory and emotion, but how the DMN regulates memory and anxiety from the perspective of the whole DMN structural network remains unknown. We used multimodal neuroimaging methods to investigate the structural connectivity pattern of the DMN and the association of its network properties with memory and anxiety in 205 young healthy subjects with age ranging from 18 to 29 years old. The Group ICA method was used to extract the DMN component from functional magnetic resonance imaging (fMRI) data and a probabilistic fiber tractography technique based on DTI data was applied to construct the global structural connectivity pattern of the DMN. Then we used the graph theory method to analyze the DMN structural network and found that memory quotient (MQ) score was significantly positively correlated with the global and local efficiency of the DMN whereas anxiety was found to be negatively correlated with the efficiency. The strong structural connectivity between multiple brain regions within DMN may reflect that the DMN has certain structural basis. Meanwhile, the results we found that the network efficiency of the DMN were related to memory and anxiety measures, indicated that the DMN may play a role in the memory and anxiety. PMID:26635544

  13. Mathematics Anxiety, Working Memory, and Mathematics Performance in Secondary-School Children.

    PubMed

    Passolunghi, Maria C; Caviola, Sara; De Agostini, Ruggero; Perin, Chiara; Mammarella, Irene C

    2016-01-01

    Mathematics anxiety (MA) has been defined as "a feeling of tension and anxiety that interferes with the manipulation of numbers and the solving of math problems in a wide variety of ordinary life and academic situations." Previous studies have suggested that a notable proportion of children in primary and secondary school suffer from MA, which is negatively correlated with calculation skills. The processing efficiency and attentional control theories suggest that working memory (WM) also plays an important part in such anxious feelings. The present study aimed to analyze the academic achievement and cognitive profiles of students with high math anxiety (HMA) and low math anxiety (LMA). Specifically, 32 students with HMA and 34 with LMA matched for age, gender, generalized anxiety, and vocabulary attending sixth to eighth grades were selected from a larger sample. The two groups were tested on reading decoding, reading comprehension, mathematics achievement, and on verbal short-term memory and WM. Our findings showed that HMA students were weak in several measures of mathematics achievement, but not in reading and writing skills, and that students with HMA reported lower scores on short-term memory and WM performances (with associated difficulties in inhibiting irrelevant information) than children with LMA. In addition, a logistic regression showed that weaknesses in inhibitory control and fact retrieval were the strongest variables for classifying children as having HMA or LMA.

  14. Mathematics Anxiety, Working Memory, and Mathematics Performance in Secondary-School Children.

    PubMed

    Passolunghi, Maria C; Caviola, Sara; De Agostini, Ruggero; Perin, Chiara; Mammarella, Irene C

    2016-01-01

    Mathematics anxiety (MA) has been defined as "a feeling of tension and anxiety that interferes with the manipulation of numbers and the solving of math problems in a wide variety of ordinary life and academic situations." Previous studies have suggested that a notable proportion of children in primary and secondary school suffer from MA, which is negatively correlated with calculation skills. The processing efficiency and attentional control theories suggest that working memory (WM) also plays an important part in such anxious feelings. The present study aimed to analyze the academic achievement and cognitive profiles of students with high math anxiety (HMA) and low math anxiety (LMA). Specifically, 32 students with HMA and 34 with LMA matched for age, gender, generalized anxiety, and vocabulary attending sixth to eighth grades were selected from a larger sample. The two groups were tested on reading decoding, reading comprehension, mathematics achievement, and on verbal short-term memory and WM. Our findings showed that HMA students were weak in several measures of mathematics achievement, but not in reading and writing skills, and that students with HMA reported lower scores on short-term memory and WM performances (with associated difficulties in inhibiting irrelevant information) than children with LMA. In addition, a logistic regression showed that weaknesses in inhibitory control and fact retrieval were the strongest variables for classifying children as having HMA or LMA. PMID:26869951

  15. Mathematics Anxiety, Working Memory, and Mathematics Performance in Secondary-School Children

    PubMed Central

    Passolunghi, Maria C.; Caviola, Sara; De Agostini, Ruggero; Perin, Chiara; Mammarella, Irene C.

    2016-01-01

    Mathematics anxiety (MA) has been defined as “a feeling of tension and anxiety that interferes with the manipulation of numbers and the solving of math problems in a wide variety of ordinary life and academic situations.” Previous studies have suggested that a notable proportion of children in primary and secondary school suffer from MA, which is negatively correlated with calculation skills. The processing efficiency and attentional control theories suggest that working memory (WM) also plays an important part in such anxious feelings. The present study aimed to analyze the academic achievement and cognitive profiles of students with high math anxiety (HMA) and low math anxiety (LMA). Specifically, 32 students with HMA and 34 with LMA matched for age, gender, generalized anxiety, and vocabulary attending sixth to eighth grades were selected from a larger sample. The two groups were tested on reading decoding, reading comprehension, mathematics achievement, and on verbal short-term memory and WM. Our findings showed that HMA students were weak in several measures of mathematics achievement, but not in reading and writing skills, and that students with HMA reported lower scores on short-term memory and WM performances (with associated difficulties in inhibiting irrelevant information) than children with LMA. In addition, a logistic regression showed that weaknesses in inhibitory control and fact retrieval were the strongest variables for classifying children as having HMA or LMA. PMID:26869951

  16. State Anxiety and Working Memory in Children: A Test of Processing Efficiency Theory

    ERIC Educational Resources Information Center

    Hadwin, Julie A.; Brogan, Joanna; Stevenson, Jim

    2005-01-01

    This study investigated the effect of individual differences in state anxiety on tasks tapping the central executive, phonological, and visuo-spatial components of working memory (WM). It was designed to test Eysenck and Calvo's processing efficiency theory (PET) which suggests that the phonological and executive components of WM may be important…

  17. Processing Efficiency in Preschoolers' Memory Span: Individual Differences Related to Age and Anxiety

    ERIC Educational Resources Information Center

    Visu-Petra, Laura; Miclea, Mircea; Cheie, Lavinia; Benga, Oana

    2009-01-01

    In self-paced auditory memory span tasks, the microanalysis of response timing measures represents a developmentally sensitive measure, providing insights into the development of distinct processing rates during recall performance. The current study first examined the effects of age and trait anxiety on span accuracy (effectiveness) and response…

  18. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness

    PubMed Central

    Hamilton, Trevor James; Kwan, Garfield T.; Gallup, Joshua; Tresguerres, Martin

    2016-01-01

    Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab. PMID:26806870

  19. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

    PubMed Central

    Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

    2015-01-01

    Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be—in part—due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID

  20. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients.

    PubMed

    Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

    2015-01-01

    Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be-in part-due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID:26191015

  1. Do negative affect characteristics and subjective memory concerns increase risk for late life anxiety?

    PubMed

    Wilkes, Chelsey M; Wilson, Helen W; Woodard, John L; Calamari, John E

    2013-08-01

    To better understand the development and exacerbation of late-life anxiety, we tested a risk model positing that trait negative affect (NA) characteristics would interact with cognitive functioning, thereby increasing some older adults' risk for increased anxiety symptoms. The moderator-mediator model consisted of measures of NA, cognitive functioning, and their interaction, as predictors of later Hamilton Anxiety Rating Scale scores (HARS) via a mediational process, subjective memory concerns (SMCs). Older adults (aged 65-years and over; M(age)=76.7 years, SD=6.90 years) completed evaluations four times over approximately 18 months. A latent growth curve model including Anxiety Sensitivity Index total score (ASI), Mattis Dementia Rating Scale-2 (DRS) total raw score, the ASI×DRS interaction, a SMC measure as mediator, HARS intercept (scores at times 3 and 4), and HARS slope provided good fit. The ASI×DRS-2 interaction at Time 1 predicted HARS slope score (β=-.34, p<.05). When ASI score was high, stronger cognitive functioning was associated with fewer anxiety symptoms. The indirect effect of ASI score predicting HARS score 18-months later through the SMC mediator was statistically significant (β=.08, p<.05). Results suggest that the cognitive functioning changes associated with aging might contribute to the development of anxiety symptoms in older adults with specific NA traits. Implications for predicting and preventing late life anxiety disorders are discussed.

  2. Anxiety

    MedlinePlus

    ... to leave home. These people have anxiety disorders. Types include Panic disorder Obsessive-compulsive disorder Post-traumatic stress disorder Phobias Generalized anxiety disorder Treatment can involve ...

  3. Working Memory at Work: How the Updating Process Alters the Nature of Working Memory Transfer

    PubMed Central

    Zhang, Yanmin; Verhaeghen, Paul; Cerella, John

    2011-01-01

    In three N-Back experiments, we investigated components of the process of working memory (WM) updating, more specifically access to items stored outside the focus of attention and transfer from the focus to the region of WM outside the focus. We used stimulus complexity as a marker. We found that when WM transfer occurred under full attention, it was slow and highly sensitive to stimulus complexity, much more so than WM access. When transfer occurred in conjunction with access, however, it was fast and no longer sensitive to stimulus complexity. Thus the updating context altered the nature of WM processing: The dual-task situation (transfer in conjunction with access) drove memory transfer into a more efficient mode, indifferent to stimulus complexity. In contrast, access times consistently increased with complexity, unaffected by the processing context. This study reinforces recent reports that retrieval is a (perhaps the) key component of working memory functioning. PMID:22105718

  4. CO2-induced ocean acidification increases anxiety in Rockfish via alteration of GABAA receptor functioning

    PubMed Central

    Hamilton, Trevor James; Holcombe, Adam; Tresguerres, Martin

    2014-01-01

    The average surface pH of the ocean is dropping at a rapid rate due to the dissolution of anthropogenic CO2, raising concerns for marine life. Additionally, some coastal areas periodically experience upwelling of CO2-enriched water with reduced pH. Previous research has demonstrated ocean acidification (OA)-induced changes in behavioural and sensory systems including olfaction, which is due to altered function of neural gamma-aminobutyric acid type A (GABAA) receptors. Here, we used a camera-based tracking software system to examine whether OA-dependent changes in GABAA receptors affect anxiety in juvenile Californian rockfish (Sebastes diploproa). Anxiety was estimated using behavioural tests that measure light/dark preference (scototaxis) and proximity to an object. After one week in OA conditions projected for the next century in the California shore (1125 ± 100 µatm, pH 7.75), anxiety was significantly increased relative to controls (483 ± 40 µatm CO2, pH 8.1). The GABAA-receptor agonist muscimol, but not the antagonist gabazine, caused a significant increase in anxiety consistent with altered Cl− flux in OA-exposed fish. OA-exposed fish remained more anxious even after 7 days back in control seawater; however, they resumed their normal behaviour by day 12. These results show that OA could severely alter rockfish behaviour; however, this effect is reversible. PMID:24285203

  5. Images of the self in social anxiety: effects on the retrieval of autobiographical memories.

    PubMed

    Stopa, Lusia; Jenkins, Andy

    2007-12-01

    Cognitive models of social phobia propose that negative self-images play an important role in maintaining anxiety. This study examines the effect of holding a positive or a negative image in mind during a speech on the retrieval of autobiographical memories. Twenty high socially anxious participants performed a standard autobiographical memory task (AMT), which used positive, negative and neutral cue words. Participants performed the AMT twice: once after giving a speech holding a positive image and once while holding a negative image. Participants were more anxious and rated their performance worse in the negative image condition. Negative memories were retrieved faster in the negative image condition and positive memories were retrieved faster in the positive image condition. In the negative image condition, positive memories were retrieved more slowly than either negative or neutral memories. Inhibition and facilitation are proposed as two processes that could explain the effects of differently valenced imagery on autobiographical memory. The clear evidence for an inhibitory effect on positive autobiographical memories in the negative imagery condition is considered in relation to Brewin's [(2006). Understanding cognitive behaviour therapy: A retrieval competition account. Behaviour Research and Therapy, 44, 765-784] retrieval competition hypothesis. The paper concludes with a brief discussion of the potential role of inhibition in imagery rescripting. PMID:17931596

  6. Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder.

    PubMed

    Wingo, Aliza P; Gibson, Greg

    2015-01-01

    Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD. PMID:25300922

  7. A mouse model of anxiety molecularly characterized by altered protein networks in the brain proteome.

    PubMed

    Szego, Eva M; Janáky, Tamás; Szabó, Zoltán; Csorba, Attila; Kompagne, Hajnalka; Müller, Géza; Lévay, György; Simor, Attila; Juhász, Gábor; Kékesi, Katalin A

    2010-02-01

    Recently, several attempts have been made to describe changes related to certain anxiety states in the proteome of experimental animal models. However, these studies are restricted by limitations regarding the number and correct identification of separated proteins. Moreover, the application of a systems biology approach to discover the molecular mechanisms of anxiety requires genetically homogenous inbred animal models. Therefore, we developed a novel mouse model of anxiety using a combination of crossbreeding (inbred for 35 generations) and behavioral selection. We found significant changes in 82 proteins in the total brain proteome compared to the control proteome. Thirty-four of these proteins had been previously identified in other anxiety, depression or repeated psychosocial stress studies. The identified proteins are associated with different cellular functions, including synaptic transmission, metabolism, proteolysis, protein biosynthesis and folding, cytoskeletal proteins, brain development and neurogenesis, oxidative stress, signal transduction. Our proteomics data suggest that alterations in serotonin receptor-associated proteins, in the carbohydrate metabolism, in the cellular redox system and in synaptic docking are all involved in anxiety.

  8. Increased anxiety and impaired spatial memory in young adult rats following adolescent exposure to methylone.

    PubMed

    Daniel, Jollee J; Hughes, Robert N

    2016-01-01

    This study investigated the possibility that treatment of adolescent rats with the substituted cathinone, 3,4-methylenedioxymethcathinone (methylone), might result in heightened anxiety and/or impaired memory during early adulthood, as has been shown for other designer drugs. For 10 consecutive days from 35days after birth (PND35-44, early adolescence) or 45days after birth (PND45-54, late adolescence), male and female PVG/c rats were administered saline or 8.0mg/kg methylone via intraperitoneal injection. When 90days old (early adulthood), their anxiety-related behavior was recorded in an open field and a light/dark box. Acoustic startle amplitude was also measured as well as their spatial memory which was determined by their ability to detect which arm of a Y maze had changed in brightness between an acquisition and a retention trial. Previously methylone-treated rats showed increased anxiety-related behavior only in the open field as reflected in decreased ambulation, and increased corner occupancy and defecation. In the latter two cases, the increases depended on the age of treatment. Also, for defecation, only male rats were affected. In addition, methylone-treated rats displayed signs of impaired spatial memory, independent of anxiety, through their reduced ability to detect a novel changed Y-maze arm. The results of the study suggested some possible consequences in adulthood of methylone use during adolescence. There were also several examples of female rats exhibiting higher overall frequencies of activity and anxiety-related responding than males that were consistent with them being the more active and less anxious of the two sexes. PMID:27178814

  9. Anxiety and Depression in Academic Performance: An Exploration of the Mediating Factors of Worry and Working Memory

    ERIC Educational Resources Information Center

    Owens, Matthew; Stevenson, Jim; Hadwin, Julie A.; Norgate, Roger

    2012-01-01

    Anxiety and depression are linked to lower academic performance. It is proposed that academic performance is reduced in young people with high levels of anxiety or depression as a function of increased test-specific worry that impinges on working memory central executive processes. Participants were typically developing children (12 to…

  10. Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice.

    PubMed

    Moseley, Amy E; Williams, Michael T; Schaefer, Tori L; Bohanan, Cynthia S; Neumann, Jon C; Behbehani, Michael M; Vorhees, Charles V; Lingrel, Jerry B

    2007-01-17

    Several disorders have been associated with mutations in Na,K-ATPase alpha isoforms (rapid-onset dystonia parkinsonism, familial hemiplegic migraine type-2), as well as reduction in Na,K-ATPase content (depression and Alzheimer's disease), thereby raising the issue of whether haploinsufficiency or altered enzymatic function contribute to disease etiology. Three isoforms are expressed in the brain: the alpha1 isoform is found in many cell types, the alpha2 isoform is predominantly expressed in astrocytes, and the alpha3 isoform is exclusively expressed in neurons. Here we show that mice heterozygous for the alpha2 isoform display increased anxiety-related behavior, reduced locomotor activity, and impaired spatial learning in the Morris water maze. Mice heterozygous for the alpha3 isoform displayed spatial learning and memory deficits unrelated to differences in cued learning in the Morris maze, increased locomotor activity, an increased locomotor response to methamphetamine, and a 40% reduction in hippocampal NMDA receptor expression. In contrast, heterozygous alpha1 isoform mice showed increased locomotor response to methamphetamine and increased basal and stimulated corticosterone in plasma. The learning and memory deficits observed in the alpha2 and alpha3 heterozygous mice reveal the Na,K-ATPase to be an important factor in the functioning of pathways associated with spatial learning. The neurobehavioral changes seen in heterozygous mice suggest that these mouse models may be useful in future investigations of the associated human CNS disorders.

  11. Anxiety.

    PubMed

    Dean, Erin

    2016-07-13

    Essential facts Anxiety is the feeling of fear that occurs when faced with threatening or stressful situations. It is a normal response when confronted with danger, but, if it is overwhelming or the feeling persists, it could be regarded as an anxiety disorder. The Royal College of Psychiatrists says anxiety disorders, including panic disorder, post-traumatic stress disorder and social anxiety disorder, affect about one in ten. PMID:27406490

  12. Anxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study.

    PubMed

    Pietrzak, Robert H; Scott, J Cobb; Neumeister, Alexander; Lim, Yen Ying; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Szoeke, Cassandra; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

    2014-01-01

    Although beta-amyloid, anxiety and depression have linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.

  13. Altered responsiveness of BNST and amygdala neurons in trauma-induced anxiety.

    PubMed

    Rodríguez-Sierra, O E; Goswami, S; Turesson, H K; Pare, D

    2016-01-01

    A highly conserved network of brain structures regulates the expression of fear and anxiety in mammals. Many of these structures display abnormal activity levels in post-traumatic stress disorder (PTSD). However, some of them, like the bed nucleus of the stria terminalis (BNST) and amygdala, are comprised of several small sub-regions or nuclei that cannot be resolved with human neuroimaging techniques. Therefore, we used a well-characterized rat model of PTSD to compare neuronal properties in resilient vs PTSD-like rats using patch recordings obtained from different BNST and amygdala regions in vitro. In this model, a persistent state of extreme anxiety is induced in a subset of susceptible rats following predatory threat. Previous animal studies have revealed that the central amygdala (CeA) and BNST are differentially involved in the genesis of fear and anxiety-like states, respectively. Consistent with these earlier findings, we found that between resilient and PTSD-like rats were marked differences in the synaptic responsiveness of neurons in different sectors of BNST and CeA, but whose polarity was region specific. In light of prior data about the role of these regions, our results suggest that control of fear/anxiety expression is altered in PTSD-like rats such that the influence of CeA is minimized whereas that of BNST is enhanced. A model of the amygdalo-BNST interactions supporting the PTSD-like state is proposed. PMID:27434491

  14. Working Memory Training and CBT Reduces Anxiety Symptoms and Attentional Biases to Threat: A Preliminary Study.

    PubMed

    Hadwin, Julie A; Richards, Helen J

    2016-01-01

    Research indicates that cognitive processes linked to the detection of threat stimuli are associated with poor attentional control, placing children and adolescents at increased risk for the development of anxious affect. The current study aimed to provide preliminary data to assess whether an intervention designed to improve attentional control (via working memory; WM) would lead to better performance in tests of WM and would be associated with positive changes in symptoms of trait and test anxiety, increased inhibitory control and reduced attention to threat. Forty adolescents aged 11-14 years who reported elevated anxiety and low attentional control were randomly allocated to a WM training or an active cognitive behavioural therapy (CBT) control group. Post intervention, WM training was associated with greater improvements (versus. CBT) in trained WM tasks. Both groups, however, reported fewer anxiety symptoms, demonstrated increased inhibitory control and a reduction in attentional biases to threat post intervention and these results were maintained at follow up. The study provides indicative evidence which suggests that WM training has similar benefits to a more traditional CBT intervention on reduced anxiety and attentional biases for threat. Future research should aim to replicate the findings in a large sample size and explore the broader impact of training on day-to-day functioning. In addition, further research is needed to identify which participants benefit most from different interventions (using baseline characteristics) on treatment compliance and outcome.

  15. Individual differences in anxiety predict neural measures of visual working memory for untrustworthy faces.

    PubMed

    Meconi, Federica; Luria, Roy; Sessa, Paola

    2014-12-01

    When facing strangers, one of the first evaluations people perform is to implicitly assess their trustworthiness. However, the underlying processes supporting trustworthiness appraisal are poorly understood. We hypothesized that visual working memory (VWM) maintains online face representations that are sensitive to physical cues of trustworthiness, and that differences among individuals in representing untrustworthy faces are associated with individual differences in anxiety. Participants performed a change detection task that required encoding and maintaining for a short interval the identity of one face parametrically manipulated to be either trustworthy or untrustworthy. The sustained posterior contralateral negativity (SPCN), an event-related component (ERP) time-locked to the onset of the face, was used to index the resolution of face representations in VWM. Results revealed greater SPCN amplitudes for trustworthy faces when compared with untrustworthy faces, indicating that VWM is sensitive to physical cues of trustworthiness, even in the absence of explicit trustworthiness appraisal. In addition, differences in SPCN amplitude between trustworthy and untrustworthy faces correlated with participants' anxiety, indicating that healthy college students with sub-clinical high anxiety levels represented untrustworthy faces in greater detail compared with students with sub-clinical low anxiety levels. This pattern of findings is discussed in terms of the high flexibility of aversive/avoidance and appetitive/approach motivational systems. PMID:24493843

  16. Working Memory Training and CBT Reduces Anxiety Symptoms and Attentional Biases to Threat: A Preliminary Study

    PubMed Central

    Hadwin, Julie A.; Richards, Helen J.

    2016-01-01

    Research indicates that cognitive processes linked to the detection of threat stimuli are associated with poor attentional control, placing children and adolescents at increased risk for the development of anxious affect. The current study aimed to provide preliminary data to assess whether an intervention designed to improve attentional control (via working memory; WM) would lead to better performance in tests of WM and would be associated with positive changes in symptoms of trait and test anxiety, increased inhibitory control and reduced attention to threat. Forty adolescents aged 11–14 years who reported elevated anxiety and low attentional control were randomly allocated to a WM training or an active cognitive behavioural therapy (CBT) control group. Post intervention, WM training was associated with greater improvements (versus. CBT) in trained WM tasks. Both groups, however, reported fewer anxiety symptoms, demonstrated increased inhibitory control and a reduction in attentional biases to threat post intervention and these results were maintained at follow up. The study provides indicative evidence which suggests that WM training has similar benefits to a more traditional CBT intervention on reduced anxiety and attentional biases for threat. Future research should aim to replicate the findings in a large sample size and explore the broader impact of training on day-to-day functioning. In addition, further research is needed to identify which participants benefit most from different interventions (using baseline characteristics) on treatment compliance and outcome. PMID:26869956

  17. Spatial anxiety relates to spatial abilities as a function of working memory in children.

    PubMed

    Ramirez, Gerardo; Gunderson, Elizabeth A; Levine, Susan C; Beilock, Sian L

    2012-01-01

    Spatial ability is a strong predictor of students' pursuit of higher education in science and mathematics. However, very little is known about the affective factors that influence individual differences in spatial ability, particularly at a young age. We examine the role of spatial anxiety in young children's performance on a mental rotation task. We show that even at a young age, children report experiencing feelings of nervousness at the prospect of engaging in spatial activities. Moreover, we show that these feelings are associated with reduced mental rotation ability among students with high but not low working memory (WM). Interestingly, this WM × spatial anxiety interaction was only found among girls. We discuss these patterns of results in terms of the problem-solving strategies that boys versus girls use in solving mental rotation problems.

  18. Effects of environmental enrichment on anxiety responses, spatial memory and cytochrome c oxidase activity in adult rats.

    PubMed

    Sampedro-Piquero, P; Zancada-Menendez, C; Begega, A; Rubio, S; Arias, J L

    2013-09-01

    We have studied the effect of an environmental enrichment (EE) protocol in adult Wistar rats on the activity in the elevated zero-maze (EZM), performance in the radial-arm water maze (RAWM) and we have also examined the changes in the neuronal metabolic activity of several brain regions related to anxiety response and spatial memory through cytochrome c oxidase histochemistry (COx). Our EE protocol had anxiolytic effect in the EZM; the animals spent more time and made more entries into the open quadrants, they had lower latency to enter into the open quadrant and lower levels of defecation. Also, the EE group showed fewer working memory and reference memory errors, as well as lesser distance travelled in the first day of the spatial training. In relation to the neuronal metabolic activity, EE reduced the COx activity in brain regions related to anxiety response, such as the infralimbic cortex, the paraventricular thalamic and hypothalamic nucleus, the basolateral amygdala, and the ventral hippocampus. Interestingly, there were no significant differences between groups in the dorsal hippocampus, more related to spatial cognition. These results suggest a beneficial effect of EE on spatial memory as a result of reducing anxiety levels and the COx activity in brain regions involved in anxiety response. We also found a differential pattern of activation inside the hippocampus, suggesting that the dorsal hippocampus has a preferential involvement in spatial learning and memory, whereas the ventral hippocampus has a role in anxiety response.

  19. Intrusive imagery in severe health anxiety: Prevalence, nature and links with memories and maintenance cycles

    PubMed Central

    Muse, Kate; McManus, Freda; Hackmann, Ann; Williams, Matthew; Williams, Mark

    2010-01-01

    Increased understanding of the nature and role of intrusive imagery has contributed to the development of effective treatment protocols for some anxiety disorders. However, intrusive imagery in severe health anxiety (hypochondriasis) has been comparatively neglected. Hence, the current study investigates the prevalence, nature and content of intrusive imagery in 55 patients who met DSM-IV-TR (APA, 2000) criteria for the diagnosis of hypochondriasis. A semi-structured interview was used to assess the prevalence, nature and possible role of intrusive imagery in this disorder. Over 78% of participants reported experiencing recurrent, distressing intrusive images, the majority (72%) of which either were a memory of an earlier event or were strongly associated with a memory. The images tended to be future orientated, and were reliably categorised into four themes: i) being told ‘the bad news’ that you have a serious/life threatening-illness (6.9%), ii) suffering from a serious or life-threatening illness (34.5%), iii) death and dying due to illness (22.4%) and iv) impact of own death or serious illness on loved ones (36.2%). Participants reported responding to experiencing intrusive images by engaging in avoidance, checking, reassurance seeking, distraction and rumination. Potential treatment implications and links to maintenance cycles are considered. PMID:20627270

  20. Impact of Working Memory Load on Cognitive Control in Trait Anxiety: An ERP Study

    PubMed Central

    Qi, Senqing; Zeng, Qinghong; Luo, Yangmei; Duan, Haijun; Ding, Cody; Hu, Weiping; Li, Hong

    2014-01-01

    Whether trait anxiety is associated with a general impairment of cognitive control is a matter of debate. This study investigated whether and how experimentally manipulated working memory (WM) load modulates the relation between trait anxiety and cognitive control. This question was investigated using a dual-task design in combination with event-related potentials. Participants were required to remember either one (low WM load) or six letters (high WM load) while performing a flanker task. Our results showed that a high WM load disrupted participants' ability to overcome distractor interference and this effect was exacerbated for the high trait-anxious (HTA) group. This exacerbation was reflected by larger interference effects (i.e., incongruent minus congruent) on reaction times (RTs) and N2 amplitudes for the HTA group than for the low trait-anxious group under high WM load. The two groups, however, did not differ in their ability to inhibit task-irrelevant distractors under low WM load, as indicated by both RTs and N2 amplitudes. These findings underscore the significance of WM-related cognitive demand in contributing to the presence (or absence) of a general cognitive control deficit in trait anxiety. Furthermore, our findings show that when limited WM resources are depleted by high WM load, HTA individuals exhibit less efficient recruitments of cognitive control required for the inhibition of distractors, therefore resulting in a greater degree of response conflict. PMID:25369121

  1. Manufactured Memory, Altered Belief and Self Report Mirage: The Alleged False Memory of Jean Piaget Revisited.

    ERIC Educational Resources Information Center

    Leavitt, Frank

    1999-01-01

    It is argued that a Jean Piaget anecdote about an alleged memory implanted in a young child leading to both a visual and semantic memory that persists despite disconfirming evidence is entirely different than the recovered memory debate, which is about the alleged introduction of memories to grown adults. (CR)

  2. Anxiety

    MedlinePlus

    ... the Experts Tools & Tips Latest Research Related Topics COPD Delirium Dementia Depression Drug and Substance Abuse High Blood Pressure Join our e-newsletter! Aging & Health A to Z Anxiety Basic Facts & Information ...

  3. Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone.

    PubMed

    Silva, Anatildes Feitosa; Sousa, Diego Silveira; Medeiros, André Macêdo; Macêdo, Priscila Tavares; Leão, Anderson Henrique; Ribeiro, Alessandra Mussi; Izídio, Geison Souza; Silva, Regina Helena

    2016-10-01

    Studies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women. PMID:27208614

  4. Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder.

    PubMed

    Dias, Gisele Pereira; Bevilaqua, Mário Cesar do Nascimento; da Luz, Anna Claudia Domingos Silveira; Fleming, Renata Lopes; de Carvalho, Lítia Alves; Cocks, Graham; Beckman, Danielle; Hosken, Lucas Costa; de Sant'Anna Machado, William; Corrêa-e-Castro, Ana Carolina; Mousovich-Neto, Felippe; de Castro Gomes, Vítor; Bastos, Gilmara de Nazareth Tavares; Kubrusly, Regina Célia Cussa; da Costa, Vânia Maria Corrêa; Srivastava, Deepak; Landeira-Fernandez, Jesus; Nardi, Antonio Egidio; Thuret, Sandrine; Gardino, Patricia Franca

    2014-04-15

    Generalized anxiety disorder (GAD) is highly prevalent and incapacitating. Here we used the Carioca High-Conditioned Freezing (CHF) rats, a previously validated animal model for GAD, to identify biomarkers and structural changes in the hippocampus that could be part of the underlying mechanisms of their high-anxiety profile. Spatial and fear memory was assessed in the Morris water maze and passive avoidance test. Serum corticosterone levels, immunofluorescence for glucocorticoid receptors (GR) in the dentate gyrus (DG), and western blotting for hippocampal brain derived neurotrophic factor (BDNF) were performed. Immunohistochemistry for markers of cell proliferation (bromodeoxiuridine/Ki-67), neuroblasts (doublecortin), and cell survival were undertaken in the DG, along with spine staining (Golgi) and dendritic arborization tracing. Hippocampal GABA release was assessed by neurochemical assay. Fear memory was higher among CHF rats whilst spatial learning was preserved. Serum corticosterone levels were increased, with decreased GR expression. No differences were observed in hippocampal cell proliferation/survival, but the number of newborn neurons was decreased, along with their number and length of tertiary dendrites. Increased expression of proBDNF and dendritic spines was observed; lower ratio of GABA release in the hippocampus was also verified. These findings suggest that generalized anxiety/fear could be associated with different hippocampal biomarkers, such as increased spine density, possibly as a compensatory mechanism for the decreased hippocampal number of neuroblasts and dendritic arborization triggered by high corticosterone. Disruption of GABAergic signaling and BDNF impairment are also proposed as part of the hippocampal mechanisms possibly underlying the anxious phenotype of this model. PMID:24462725

  5. Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone.

    PubMed

    Silva, Anatildes Feitosa; Sousa, Diego Silveira; Medeiros, André Macêdo; Macêdo, Priscila Tavares; Leão, Anderson Henrique; Ribeiro, Alessandra Mussi; Izídio, Geison Souza; Silva, Regina Helena

    2016-10-01

    Studies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women.

  6. Hormonal contraception usage is associated with altered memory for an emotional story.

    PubMed

    Nielsen, Shawn E; Ertman, Nicole; Lakhani, Yasmeen S; Cahill, Larry

    2011-09-01

    Substantial evidence now documents sex-related influences on the neurobiology of emotional memory. Robust sex influences exist, for example, on the amygdala's role in emotional memory formation, as well as on retention of central information (gist) and detail for an emotional event. Evidence also suggests that the well-documented effects of stress hormones on memory depend upon sex hormone levels. Since hormonal contraception alters sex hormone levels, and must by extension alter sex/stress hormone interactions in memory, we examined whether the use of hormonal contraception also alters memory for an emotional story. Two groups of healthy female subjects--one naturally cycling, one using hormonal contraception--viewed either a brief, emotionally arousing story, or a closely matched, but more emotionally neutral story. Each subject's eye movements and pupil dilation changes were recorded as they viewed the story. Additionally, saliva samples were taken throughout the experimental session to examine salivary alpha-amylase, a biomarker for norepinephrine. A surprise free recall test one week later measured story memory in all subjects. Naturally cycling women exhibited enhanced memory of story details, but not of central information (gist), in the emotional compared with neutral story conditions. In contrast, women using hormonal contraception exhibited enhanced memory of gist, but not story details, in the emotional compared with neutral story conditions. Analysis of eye movements made while watching the stories indicated that the differences in memory could not be attributed either to a differential attention focus or to the degree of arousal induced by the stories in the two groups. These findings suggest that the use of hormonal contraception alters memory for an emotional event, perhaps by altering sex/stress hormone interactions in memory formation. They also suggest that further investigation of the mnemonic effects of these very widely used treatments is

  7. What Was I Supposed to Do? Effects of Individual Differences in Age and Anxiety on Preschoolers' Prospective Memory

    ERIC Educational Resources Information Center

    Cheie, Lavinia; Miclea, Mircea; Visu-Petra, Laura

    2014-01-01

    Prospective memory (PM) refers to remembering to perform a previously planned action at the appropriate time or in the appropriate context. The present study investigated the effects of individual differences in age and trait anxiety on PM performance in 3-5- and 5-7-year-olds. Two types of PM measures were used: an event-based task, requiring…

  8. Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection.

    PubMed

    Smelser, Lisa K; Walker, Callum; Burns, Erin M; Curry, Michael; Black, Nathanael; Metzler, Jennifer A; McDowell, Susan A; Bruns, Heather A

    2016-01-01

    Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function. PMID:26927218

  9. Early Life Manipulations Alter Learning and Memory in Rats

    PubMed Central

    Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.

    2012-01-01

    Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985

  10. Strain and sex differences in brain and behaviour of adult rats: Learning and memory, anxiety and volumetric estimates.

    PubMed

    Keeley, R J; Bye, C; Trow, J; McDonald, R J

    2015-07-15

    Alterations in behaviour can arise through a number of factors, including strain and sex. Here, we explored strain and sex differences between Long-Evans (LER) and Wistar (WR) male and female rats that had been trained in a myriad of behavioural tasks. Tests included those assessing motor learning (skilled reaching task), spatial learning and memory (Morris water task), contextual learning (discriminative fear-conditioning to context) and anxiety behaviour (elevated plus maze). Following behavioural assessment, associated brain areas were examined for volumetric differences, including the hippocampus and its subregions, prefrontal cortex areas and the amygdala. LER and WR differed in their rates of performance in the skilled reaching task throughout the training period. Overall, LER outperformed WR in tasks related to contextual and spatial learning, although this was not accompanied by larger volumes of associated brain areas. Males outperformed females in spatial learning, and females outperformed males in the contextual fear-conditioning task and had an associated larger amygdalar volume, although these sexual dimorphisms were only observed within the LER strain. Overall, this study highlights differences between these two rat strains as well as highlights that larger volumetric estimates of brain areas do not always confer improved function of associated behaviours.

  11. Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder.

    PubMed

    Moon, Chung-Man; Sundaram, Thirunavukkarasu; Choi, Nam-Gil; Jeong, Gwang-Woo

    2016-08-30

    Generalized anxiety disorder (GAD) is associated with brain functional and morphological changes in connected with emotional dysregulation and cognitive deficit. This study dealt with the neural functional deficits and metabolic abnormalities in working memory (WM) task with emotion-inducing distractors in patients with GAD. Fourteen patients with GAD and 14 healthy controls underwent functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1)H-MRS) at 3T. In response to the emotional distractors in WM tasks, the patients concurrently showed higher activity in the hippocampus and lower activities in the superior occipital gyrus, superior parietal gyrus, dorsolateral prefrontal cortex (DLPFC) and precentral gyrus compared to the controls. MRS revealed significantly lower choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC. In particular, the Cho ratios were positively correlated with the brain activities based on blood oxygenation level-dependent signal change in the DLPFC. This study provides the first evidence for the association between the metabolic alterations and functional deficit in WM processing with emotion-inducing distractors in GAD. These findings will be helpful to understand the neural dysfunction in connection with WM impairment in GAD. PMID:27442922

  12. Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder.

    PubMed

    Moon, Chung-Man; Sundaram, Thirunavukkarasu; Choi, Nam-Gil; Jeong, Gwang-Woo

    2016-08-30

    Generalized anxiety disorder (GAD) is associated with brain functional and morphological changes in connected with emotional dysregulation and cognitive deficit. This study dealt with the neural functional deficits and metabolic abnormalities in working memory (WM) task with emotion-inducing distractors in patients with GAD. Fourteen patients with GAD and 14 healthy controls underwent functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1)H-MRS) at 3T. In response to the emotional distractors in WM tasks, the patients concurrently showed higher activity in the hippocampus and lower activities in the superior occipital gyrus, superior parietal gyrus, dorsolateral prefrontal cortex (DLPFC) and precentral gyrus compared to the controls. MRS revealed significantly lower choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC. In particular, the Cho ratios were positively correlated with the brain activities based on blood oxygenation level-dependent signal change in the DLPFC. This study provides the first evidence for the association between the metabolic alterations and functional deficit in WM processing with emotion-inducing distractors in GAD. These findings will be helpful to understand the neural dysfunction in connection with WM impairment in GAD.

  13. Effects of eszopiclone and zolpidem on sleep-wake behavior, anxiety-like behavior and contextual memory in rats

    PubMed Central

    Huang, Max P.; Radadia, Kushan; Macone, Brian W.; Auerbach, Sanford H.; Datta, Subimal

    2010-01-01

    At present, eszopiclone and zolpidem are the most commonly prescribed drugs for treating insomnia. Despite the established relationship between sleep disturbance and anxiety, it remains unknown whether targeted treatment for insomnia may affect acute anxiety. Therefore, the objective of this study was to examine the effects of three different doses (1, 3, and 10 mg/kg) of eszopiclone and zolpidem on the states of sleep and wakefulness, levels of anxiety-like behavior, and long-term contextual memory in footshock-induced anxious rats. The results of this study demonstrated that the administration of eszopiclone and zolpidem both were equally effective in attenuating footshock stressor-induced suppression of slow-wave sleep (SWS). The administration of eszopiclone at 1 mg/kg or zolpidem at 1 and 3 mg/kg doses showed a tendency for attenuating stressor-induced suppression of REM sleep. However, the REM sleep attenuating effects of these drugs disappeared when they were administered at higher doses. The administration of eszopiclone at 3 and 10 mg/kg doses and zolpidem at all three doses reduced the power of electroencephalographic theta band frequencies during wakefulness. In addition, the administration of eszopiclone at 1 and 3 mg/kg doses suppressed stressor-induced anxiety-like behavior. The administration of zolpidem at 1, 3, or 10 mg/kg doses was not effective in attenuating stressor-induced anxiety-like behavior. Contextual memory after administration of eszopiclone at 1 mg/kg dose had no effects, but was reduced significantly with increased dosage. Contextual memory after administration of zolpidem, at all three doses, was severely disrupted. The results of this study suggest that eszopiclone at a low dose could be used effectively to control anxiety and anxiety-induced insomnia. PMID:20153782

  14. Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice.

    PubMed

    Papaleo, Francesco; Silverman, Jill L; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L; Chadman, Kathryn K; Crawley, Jacqueline N

    2011-08-01

    BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders. PMID:21791566

  15. Early memories in social anxiety: A meaningful and enduring collaboration with my Dad.

    PubMed

    Moscovitch, David A

    2016-09-01

    In this short paper in honour of my father's Festschrift, I describe a recent collaboration with him in which we joined forces to investigate the nature of autobiographical images and memories in social anxiety. I outline our work together and the unique insights that were gleaned from our interactive contributions. Then, I reflect on how this collaboration has helped to lay the foundation for subsequent work in my lab and illuminate new directions in my program of research, enhance my career as a scientist-practitioner, and ultimately, enrich both my personal and professional identities. In so doing, I aim to highlight one of the most important and enduring aspects of my father's legacy: the profound positive impact he has on the people with whom he has worked. PMID:26994594

  16. Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

    PubMed Central

    Papaleo, Francesco; Silverman, Jill L.; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L.; Chadman, Kathryn K.; Crawley, Jacqueline N.

    2011-01-01

    BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders. PMID:21791566

  17. Intra-amygdala microinjections of chlorpheniramine impair memory formation or memory retrieval in anxiety- and fear-mediated models.

    PubMed

    Serafim, K R; Russo, P S T; Fernandes, C E M; Gianlorenço, A C L; Mattioli, R

    2016-07-01

    H1 receptor histaminergic antagonist, chlorpheniramine (CPA) participates in cognitive performance in various animal models. However, little is known regarding the effects of CPA microinjection into the amygdala on emotional behavior. The purpose of this study was to investigate whether CPA microinjection into the amygdala has the same effect on two models, one anxiety- and the other fear-mediated, in various memory stages using the elevated plus maze (EPM) and the inhibitory avoidance task (IAT) tests. Two experiments were performed with seventy-two adult male Swiss mice. Behavioral testing was performed on two consecutive days, and in both experiments, before each trial, the animals received bilateral microinjections of saline (SAL) or CPA (0.16 nmol). The animals were re-exposed to the EPM or IAT 24h after the first trial. Four experimental groups were tested: SAL-SAL, SAL-CPA, CPA-SAL and CPA-CPA. In experiment 1, a decreased open arm exploration (% open arm entries, %OAE and% open arms time, %OAT) for SAL-SAL and SAL-CPA was showed, while these measures did not decrease for the CPA-SAL and CPA-CPA groups in Trial 2. In experiment 2, an increase of retention latency in relation to training 2 for the groups SAL-SAL and CPA-SAL and a significant decrease in latency for the group SAL-CPA was revealed. These results indicate that chlorpheniramine microinjection into the amygdala impairs emotional memory acquisition and/or consolidation in the EPM and retrieval of IAT.

  18. Alterations in Memory for Text by Leading Questions.

    ERIC Educational Resources Information Center

    Robertson, Scott P.; And Others

    Two experiments were conducted to test three hypotheses related to comprehension. The hypotheses were: that actions are harder to modify than states; that implications or inferences from modified concepts would also change in memory; and that propagation of modifications would be less likely to states than to actions. The first experiment tested…

  19. Alteration in anxiety with relation to the volume of the locus ceruleus in progranulin-deficient mice.

    PubMed

    Chiba, Shuichi; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2009-10-01

    The mammalian brain exhibits sex differences with respect to structure and function. In our previous report, we found that progranulin (PGRN)-deficient (pgrn(-/-)) mice displayed an alteration in male-type behaviors, including reduced frequency of ejaculation and elevated levels of aggression and anxiety. The aim of the present study was to elucidate the role of PGRN in sex differences in anxiety. In the elevated plus maze, wild-type (pgrn(+/+)) female mice spent more time in the closed arms than the pgrn(+/+) males, suggesting that the level of anxiety was higher in females than males. On the other hand, no sex difference was observed in the pgrn(-/-) mice, and their anxiety levels were almost the same as those of the pgrn(+/+) females. To elucidate the effect of testosterone on male anxiety, male mice were castrated at 5 weeks of age and silastic tubes filled with either testosterone or cholesterol were then implanted into them for one week. These treatments did not affect anxiety in the open field in either genotypes, although the pgrn(-/-) males exhibited higher anxiety than pgrn(+/+) males. Next, we measured the volume of the paraventricular nucleus (PVN) and the locus ceruleus (LC), as these are anxiety/stress-related nuclei that are known to have sex differences in their structures. In the pgrn(+/+) mice, there was a tendency for the volume of the LC to be larger in males than females. In addition, the pgrn(-/-) mice had a larger volume of LC than the pgrn(+/+) mice, although no sexual differences were observed. The number of cells in the LC was also larger in the pgrn(-/-) than in the pgrn(+/+) mice. No significant differences in the volumes of the PVN were observed between genotypes or sexes. These results suggest that PGRN plays a role in organization of the LC, which eventually modulates anxiety in novel environments. PMID:19550107

  20. Effects of environmental enrichment on exploration, anxiety, and memory in female TgCRND8 Alzheimer mice.

    PubMed

    Görtz, Nicole; Lewejohann, Lars; Tomm, Manuel; Ambrée, Oliver; Keyvani, Kathy; Paulus, Werner; Sachser, Norbert

    2008-08-01

    After we could recently demonstrate a beneficial effect of environmental enrichment on AD-like brain pathology in female TgCRND8 mice [Ambrée O, Leimer U, Herring A, Görtz N, Sachser N, Heneka MT, et al. Reduction of amyloid angiopathy and Abeta plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways. Am J Pathol 2006;169:544-52] the present study focuses on the behavioural effects of environmental enrichment with special emphasis on learning and memory performance in this AD model. In the first experiment spontaneous exploration, locomotor activity and anxiety-related behaviour were assessed as the performance in learning tasks can be biased substantially by exploratory behavioural traits. In the second experiment spatial memory in the Barnes maze test and object recognition memory were examined. Regarding exploratory behaviour transgenic mice from standard housing condition were statistically indistinguishable from wild-type controls. Enrichment had comparable effects in both genotypes indicated by higher levels of exploration and locomotor activity. In transgenic mice the elevated plus-maze revealed less anxiety-related behaviour due to enrichment in contrast to wild-type mice that statistically did not differ in anxiety-related behaviour. Concerning learning and memory performance, cognitive deficits of standard housed transgenic mice could be demonstrated in both learning tasks. Surprisingly, in both housing conditions a significantly higher number of transgenic mice refused to explore any objects compared to wild-type mice. Furthermore, the Barnes maze test revealed deficits of the transgenic mice in spatial memory compared to wild-type mice whereas no effect of environmental enrichment was detectable. Thus environmental enrichment increased exploratory behaviour and decreased anxiety-related behaviour but could not clearly ameliorate deficits in learning and memory performance of TgCRND8 mice.

  1. Hippocampal effects of neuronostatin on memory, anxiety-like behavior and food intake in rats.

    PubMed

    Carlini, V P; Ghersi, M; Gabach, L; Schiöth, H B; Pérez, M F; Ramirez, O A; Fiol de Cuneo, M; de Barioglio, S R

    2011-12-01

    A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro-hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra-hippocampally administered at 3.0 nmol/μl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/μl and 3.0 nmol/μl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/μl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity. PMID:21978882

  2. Hippocampal effects of neuronostatin on memory, anxiety-like behavior and food intake in rats.

    PubMed

    Carlini, V P; Ghersi, M; Gabach, L; Schiöth, H B; Pérez, M F; Ramirez, O A; Fiol de Cuneo, M; de Barioglio, S R

    2011-12-01

    A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro-hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra-hippocampally administered at 3.0 nmol/μl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/μl and 3.0 nmol/μl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/μl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity.

  3. Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory.

    PubMed

    Pristerà, Andrea; Saraulli, Daniele; Farioli-Vecchioli, Stefano; Strimpakos, Georgios; Costanzi, Marco; di Certo, Maria Grazia; Cannas, Sara; Ciotti, Maria Teresa; Tirone, Felice; Mattei, Elisabetta; Cestari, Vincenzo; Canu, Nadia

    2013-11-01

    Different pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampus-dependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26-230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase-3-independent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair.

  4. When anticipation beats accuracy: Threat alters memory for dynamic scenes.

    PubMed

    Greenstein, Michael; Franklin, Nancy; Martins, Mariana; Sewack, Christine; Meier, Markus A

    2016-05-01

    Threat frequently leads to the prioritization of survival-relevant processes. Much of the work examining threat-related processing advantages has focused on the detection of static threats or long-term memory for details. In the present study, we examined immediate memory for dynamic threatening situations. We presented participants with visually neutral, dynamic stimuli using a representational momentum (RM) paradigm, and manipulated threat conceptually. Although the participants in both the threatening and nonthreatening conditions produced classic RM effects, RM was stronger for scenarios involving threat (Exps. 1 and 2). Experiments 2 and 3 showed that this effect does not generalize to the nonthreatening objects within a threatening scene, and that it does not extend to arousing happy situations. Although the increased RM effect for threatening objects by definition reflects reduced accuracy, we argue that this reduced accuracy may be offset by a superior ability to predict, and thereby evade, a moving threat.

  5. When anticipation beats accuracy: Threat alters memory for dynamic scenes.

    PubMed

    Greenstein, Michael; Franklin, Nancy; Martins, Mariana; Sewack, Christine; Meier, Markus A

    2016-05-01

    Threat frequently leads to the prioritization of survival-relevant processes. Much of the work examining threat-related processing advantages has focused on the detection of static threats or long-term memory for details. In the present study, we examined immediate memory for dynamic threatening situations. We presented participants with visually neutral, dynamic stimuli using a representational momentum (RM) paradigm, and manipulated threat conceptually. Although the participants in both the threatening and nonthreatening conditions produced classic RM effects, RM was stronger for scenarios involving threat (Exps. 1 and 2). Experiments 2 and 3 showed that this effect does not generalize to the nonthreatening objects within a threatening scene, and that it does not extend to arousing happy situations. Although the increased RM effect for threatening objects by definition reflects reduced accuracy, we argue that this reduced accuracy may be offset by a superior ability to predict, and thereby evade, a moving threat. PMID:26698159

  6. DREADD in Parvalbumin Interneurons of the Dentate Gyrus Modulates Anxiety, Social Interaction and Memory Extinction

    PubMed Central

    Zou, D.; Chen, L.; Deng, D.; Jiang, D.; Dong, F.; McSweeney, C.; Zhou, Y.; Liu, L.; Chen, G.; Wu, Y.; Mao, Y.

    2016-01-01

    Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PV-positive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3D-Gq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.

  7. DREADD in parvalbumin interneurons of the dentate gyrus modulates anxiety, social interaction and memory extinction.

    PubMed

    Zou, D; Chen, L; Deng, D; Jiang, D; Dong, F; McSweeney, C; Zhou, Y; Liu, L; Chen, G; Wu, Y; Mao, Y

    2016-01-01

    Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.

  8. DREADD in Parvalbumin Interneurons of the Dentate Gyrus Modulates Anxiety, Social Interaction and Memory Extinction

    PubMed Central

    Zou, D.; Chen, L.; Deng, D.; Jiang, D.; Dong, F.; McSweeney, C.; Zhou, Y.; Liu, L.; Chen, G.; Wu, Y.; Mao, Y.

    2016-01-01

    Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PV-positive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3D-Gq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus. PMID:26733123

  9. Basic perceptual changes that alter meaning and neural correlates of recognition memory

    PubMed Central

    Gao, Chuanji; Hermiller, Molly S.; Voss, Joel L.; Guo, Chunyan

    2015-01-01

    It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color) on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not). Abstract visual shapes (“squiggles”) were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential (ERP) correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400), implying that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition). Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates of

  10. Alterations in fear response and spatial memory in pre- and post-natal zinc supplemented rats: remediation by copper.

    PubMed

    Railey, Angela M; Micheli, Teresa L; Wanschura, Patricia B; Flinn, Jane M

    2010-05-11

    The role of zinc in the nervous system is receiving increased attention. At a time when dietary fortification and supplementation have increased the amount of zinc being consumed, little work has been done on the effects of enhanced zinc on behavior. Both zinc and copper are essential trace minerals that are acquired from the diet; under normal conditions the body protects against zinc overload, but at excessive dosages, copper deficiency has been seen. In order to examine the effect of enhanced metal administration on learning and memory, Sprague Dawley rats were given water supplemented with 10ppm Zn, 10ppm Zn+0.25ppm Cu, or normal lab water, during pre- and post-natal development. Fear conditioning tests at 4months showed significantly higher freezing rates during contextual retention and extinction and cued extinction for rats drinking water supplemented with zinc, suggesting increased anxiety compared to controls raised on lab water. During the MWM task at 9months, zinc-enhanced rats had significantly longer latencies to reach the platform compared to controls. The addition of copper to the zinc supplemented water brought freezing and latency levels closer to that of controls. These data demonstrate the importance of maintaining appropriate intake of both metals simultaneously, and show that long-term supplementation with zinc may cause alterations in memory.

  11. Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia.

    PubMed

    Karl, T; Duffy, L; Scimone, A; Harvey, R P; Schofield, P R

    2007-10-01

    Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion- and exploration-related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion- and exploration-inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task-specific anxiolytic-like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia.

  12. Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating.

    PubMed

    Carlson, G C; Lin, R E; Chen, Y; Brookshire, B R; White, R S; Lucki, I; Siegel, S J; Kim, S F

    2016-05-13

    Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression. Because Dexras1 is up-regulated during stress or by dexamethasone treatment, we included measures associated with emotion including anxiety and depression. Baseline anxiety-like measures (open field and zero maze) were not altered, nor were depression-like behavior (tail suspension). Measures of memory function yielded mixed results, with no changes in episodic memory (novel object recognition) but a significant decrement on working memory (T-maze). Alternatively, there was an increase in pre-pulse inhibition (PPI), without concomitant changes in either startle amplitude or locomotor activity. PPI data are consistent with the direction of change seen following exposure to dopamine D2 antagonists. An examination of NMDA subunit expression levels revealed an increased expression of the NR2A subunit, contrary to previous studies demonstrating down-regulation of the receptor following antipsychotic exposure (Schmitt et al., 2003) and up-regulation after exposure to isolation rearing (Turnock-Jones et al., 2009). These findings suggest a potential role for Dexras1 in modulating a selective subset of psychiatric symptoms, possibly via its interaction with NMDARs and/or other disease-related binding-partners. Furthermore, data suggest that modulating Dexras1 activity has contrasting effects on emotional, sensory and cognitive domains.

  13. Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating.

    PubMed

    Carlson, G C; Lin, R E; Chen, Y; Brookshire, B R; White, R S; Lucki, I; Siegel, S J; Kim, S F

    2016-05-13

    Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression. Because Dexras1 is up-regulated during stress or by dexamethasone treatment, we included measures associated with emotion including anxiety and depression. Baseline anxiety-like measures (open field and zero maze) were not altered, nor were depression-like behavior (tail suspension). Measures of memory function yielded mixed results, with no changes in episodic memory (novel object recognition) but a significant decrement on working memory (T-maze). Alternatively, there was an increase in pre-pulse inhibition (PPI), without concomitant changes in either startle amplitude or locomotor activity. PPI data are consistent with the direction of change seen following exposure to dopamine D2 antagonists. An examination of NMDA subunit expression levels revealed an increased expression of the NR2A subunit, contrary to previous studies demonstrating down-regulation of the receptor following antipsychotic exposure (Schmitt et al., 2003) and up-regulation after exposure to isolation rearing (Turnock-Jones et al., 2009). These findings suggest a potential role for Dexras1 in modulating a selective subset of psychiatric symptoms, possibly via its interaction with NMDARs and/or other disease-related binding-partners. Furthermore, data suggest that modulating Dexras1 activity has contrasting effects on emotional, sensory and cognitive domains. PMID:26946266

  14. Behavioral phenotype of maLPA1-null mice: increased anxiety-like behavior and spatial memory deficits

    PubMed Central

    Santin, L.J.; Bilbao, A.; Pedraza, C.; Matas-Rico, E.; López-Barroso, D.; Castilla-Ortega, E.; Sánchez-López, J.; Riquelme, R.; Varela-Nieto, I.; de la Villa, P.; Suardíaz, M.; Chun, J.; De Fonseca, F. Rodriguez; Estivill-Torrús, G.

    2016-01-01

    Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have demonstrated a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. Here we studied the phenotype of maLPA1–null mice, which bear a targeted deletion at the lpa1 locus, in a battery of tests examining neurologic performance, habituation in exploratory behavior in response to low and mild anxiety environments and spatial memory. MaLPA1-null mutants showed deficits in both olfaction and somesthesis, but not in retinal or auditory functions. Sensorimotor coordination was impaired only in the equilibrium and grasping reflexes. The mice also showed impairments in neuromuscular strength and analgesic response. No additional differences were observed in the rest of the tests used to study sensoriomotor orientation, limb reflexes, and coordinated limb use. At behavioral level, maLPA1-null mice showed an impaired exploration in the open field and increased anxiety-like response when exposed to the elevated plus maze. Furthermore, the mice exhibit impaired spatial memory retention and reduced use of spatial strategies in the Morris water maze. We propose that the LPA1 receptor may play a major role in both spatial memory and response to anxiety-like conditions. PMID:19689455

  15. Temporal memory averaging and post-encoding alterations in temporal expectation.

    PubMed

    Matell, Matthew S; Henning, Alexandra M

    2013-05-01

    Recent work in our lab has demonstrated that rats trained to associate two different reinforcement delays with two different cues will generate a scalar temporal expectation at a time between these delays when presented with the cue compound. This work demonstrates that rats will integrate distinct temporal memories at retrieval, revealing that temporal expectation need not be a veridical representation of experience. Following from this recognition that processes occurring at or after memory retrieval may transform or bias temporal expectations, we suggest that previous pharmacological work that had been interpreted as resulting from sensorial, or clock-speed, changes, may be alternatively interpreted as resulting from mnemonic alterations. We end with a brief review of the impact of post-encoding alterations of memory on behavior other than timing. PMID:23454594

  16. Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive- and Anxiety-Like Behaviors in Male and Female Offspring

    PubMed Central

    Hellemans, Kim G. C.; Verma, Pamela; Yoon, Esther; Yu, Wayne K.; Young, Allan H.; Weinberg, Joanne

    2016-01-01

    Background Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. Results We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. PMID:20102562

  17. Early blindness alters the spatial organization of verbal working memory.

    PubMed

    Bottini, Roberto; Mattioni, Stefania; Collignon, Olivier

    2016-10-01

    Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM.

  18. Early blindness alters the spatial organization of verbal working memory.

    PubMed

    Bottini, Roberto; Mattioni, Stefania; Collignon, Olivier

    2016-10-01

    Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM. PMID:27622641

  19. Math Anxiety, Working Memory, and Math Achievement in Early Elementary School

    ERIC Educational Resources Information Center

    Ramirez, Gerardo; Gunderson, Elizabeth A.; Levine, Susan C.; Beilock, Sian L.

    2013-01-01

    Although math anxiety is associated with poor mathematical knowledge and low course grades (Ashcraft & Krause, 2007), research establishing a connection between math anxiety and math achievement has generally been conducted with young adults, ignoring the emergence of math anxiety in young children. In the current study, we explored whether…

  20. Altered engagement of autobiographical memory networks in adult offspring of postnatally depressed mothers.

    PubMed

    Macdonald, Birthe; Murray, Lynne; Moutsiana, Christina; Fearon, Pasco; Cooper, Peter J; Halligan, Sarah L; Johnstone, Tom

    2016-07-01

    Maternal depression is associated with increased risk for offspring mood and anxiety disorders. One possible impact of maternal depression during offspring development is on the emotional autobiographical memory system. We investigated the neural mechanisms of emotional autobiographical memory in adult offspring of mothers with postnatal depression (N=16) compared to controls (N=21). During fMRI, recordings of participants describing one pleasant and one unpleasant situation with their mother and with a companion, were used as prompts to re-live the situations. Compared to controls we predicted the PND offspring would show: greater activation in medial and posterior brain regions implicated in autobiographical memory and rumination; and decreased activation in lateral prefrontal cortex and decreased connectivity between lateral prefrontal and posterior regions, reflecting reduced control of autobiographical recall. For negative situations, we found no group differences. For positive situations with their mothers, PND offspring showed higher activation than controls in left lateral prefrontal cortex, right frontal pole, cingulate cortex and precuneus, and lower connectivity of right middle frontal gyrus, left middle temporal gyrus, thalamus and lingual gyrus with the posterior cingulate. Our results are consistent with adult offspring of PND mothers having less efficient prefrontal regulation of personally relevant pleasant autobiographical memories. PMID:27208693

  1. Altered engagement of autobiographical memory networks in adult offspring of postnatally depressed mothers.

    PubMed

    Macdonald, Birthe; Murray, Lynne; Moutsiana, Christina; Fearon, Pasco; Cooper, Peter J; Halligan, Sarah L; Johnstone, Tom

    2016-07-01

    Maternal depression is associated with increased risk for offspring mood and anxiety disorders. One possible impact of maternal depression during offspring development is on the emotional autobiographical memory system. We investigated the neural mechanisms of emotional autobiographical memory in adult offspring of mothers with postnatal depression (N=16) compared to controls (N=21). During fMRI, recordings of participants describing one pleasant and one unpleasant situation with their mother and with a companion, were used as prompts to re-live the situations. Compared to controls we predicted the PND offspring would show: greater activation in medial and posterior brain regions implicated in autobiographical memory and rumination; and decreased activation in lateral prefrontal cortex and decreased connectivity between lateral prefrontal and posterior regions, reflecting reduced control of autobiographical recall. For negative situations, we found no group differences. For positive situations with their mothers, PND offspring showed higher activation than controls in left lateral prefrontal cortex, right frontal pole, cingulate cortex and precuneus, and lower connectivity of right middle frontal gyrus, left middle temporal gyrus, thalamus and lingual gyrus with the posterior cingulate. Our results are consistent with adult offspring of PND mothers having less efficient prefrontal regulation of personally relevant pleasant autobiographical memories.

  2. T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants

    PubMed Central

    Gangarossa, Giuseppe; Laffray, Sophie; Bourinet, Emmanuel; Valjent, Emmanuel

    2014-01-01

    The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type channel Cav3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca2+ channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations. PMID:24672455

  3. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats.

    PubMed

    Davies, Daniel R; Olson, Dawne; Meyer, Danielle L; Scholl, Jamie L; Watt, Michael J; Manzerra, Pasquale; Renner, Kenneth J; Forster, Gina L

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  4. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats

    PubMed Central

    Davies, Daniel R.; Olson, Dawne; Meyer, Danielle L.; Scholl, Jamie L.; Watt, Michael J.; Manzerra, Pasquale; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  5. Electrophysiological Correlates of Emotional Source Memory in High-Trait-Anxiety Individuals

    PubMed Central

    Cui, Lixia; Shi, Guangyuan; He, Fan; Zhang, Qin; Oei, Tian P. S.; Guo, Chunyan

    2016-01-01

    The interaction between recognition memory and emotion has become a research hotspot in recent years. Dual process theory posits that familiarity and recollection are two separate processes contributing to recognition memory, but further experimental evidence is needed. The present study explored the emotional context effects on successful and unsuccessful source retrieval amongst 15 high-trait-anxiety college students by using event-related potentials (ERPs) measurement. During study, a happy, fearful, or neutral face picture first was displayed, then a Chinese word was superimposed centrally on the picture and subjects were asked to remember the word and the corresponding type of picture. During the test participants were instructed to press one of four buttons to indicate whether the displayed word was an old or new word. And then, for the old word, indicate whether it had been shown with a fearful, happy, or neutral face during the study. ERPs were generally more positive for remembered words than for new words and the ERP difference was termed as an old/new effect. It was found that, for successful source retrieval (it meant both the item and the source were remembered accurately) between 500 and 700 ms (corresponding to a late positive component, LPC), there were significant old/new effects in all contexts. However, for unsuccessful source retrieval (it meant the correct recognition of old items matched with incorrect source attribution), there were no significant old/new effects in happy and neutral contexts, though significant old/new effects were observed in the fearful context. Between 700 and 1200 ms (corresponding to a late slow wave, LSW), there were significant old/new effects for successful source retrieval in happy and neutral contexts. However, in the fearful context, the old/new effects were reversed, ERPs were more negative for successful source retrieval compared to correct rejections. Moreover, there were significant emotion effects for

  6. Electrophysiological Correlates of Emotional Source Memory in High-Trait-Anxiety Individuals.

    PubMed

    Cui, Lixia; Shi, Guangyuan; He, Fan; Zhang, Qin; Oei, Tian P S; Guo, Chunyan

    2016-01-01

    The interaction between recognition memory and emotion has become a research hotspot in recent years. Dual process theory posits that familiarity and recollection are two separate processes contributing to recognition memory, but further experimental evidence is needed. The present study explored the emotional context effects on successful and unsuccessful source retrieval amongst 15 high-trait-anxiety college students by using event-related potentials (ERPs) measurement. During study, a happy, fearful, or neutral face picture first was displayed, then a Chinese word was superimposed centrally on the picture and subjects were asked to remember the word and the corresponding type of picture. During the test participants were instructed to press one of four buttons to indicate whether the displayed word was an old or new word. And then, for the old word, indicate whether it had been shown with a fearful, happy, or neutral face during the study. ERPs were generally more positive for remembered words than for new words and the ERP difference was termed as an old/new effect. It was found that, for successful source retrieval (it meant both the item and the source were remembered accurately) between 500 and 700 ms (corresponding to a late positive component, LPC), there were significant old/new effects in all contexts. However, for unsuccessful source retrieval (it meant the correct recognition of old items matched with incorrect source attribution), there were no significant old/new effects in happy and neutral contexts, though significant old/new effects were observed in the fearful context. Between 700 and 1200 ms (corresponding to a late slow wave, LSW), there were significant old/new effects for successful source retrieval in happy and neutral contexts. However, in the fearful context, the old/new effects were reversed, ERPs were more negative for successful source retrieval compared to correct rejections. Moreover, there were significant emotion effects for

  7. Electrophysiological Correlates of Emotional Source Memory in High-Trait-Anxiety Individuals.

    PubMed

    Cui, Lixia; Shi, Guangyuan; He, Fan; Zhang, Qin; Oei, Tian P S; Guo, Chunyan

    2016-01-01

    The interaction between recognition memory and emotion has become a research hotspot in recent years. Dual process theory posits that familiarity and recollection are two separate processes contributing to recognition memory, but further experimental evidence is needed. The present study explored the emotional context effects on successful and unsuccessful source retrieval amongst 15 high-trait-anxiety college students by using event-related potentials (ERPs) measurement. During study, a happy, fearful, or neutral face picture first was displayed, then a Chinese word was superimposed centrally on the picture and subjects were asked to remember the word and the corresponding type of picture. During the test participants were instructed to press one of four buttons to indicate whether the displayed word was an old or new word. And then, for the old word, indicate whether it had been shown with a fearful, happy, or neutral face during the study. ERPs were generally more positive for remembered words than for new words and the ERP difference was termed as an old/new effect. It was found that, for successful source retrieval (it meant both the item and the source were remembered accurately) between 500 and 700 ms (corresponding to a late positive component, LPC), there were significant old/new effects in all contexts. However, for unsuccessful source retrieval (it meant the correct recognition of old items matched with incorrect source attribution), there were no significant old/new effects in happy and neutral contexts, though significant old/new effects were observed in the fearful context. Between 700 and 1200 ms (corresponding to a late slow wave, LSW), there were significant old/new effects for successful source retrieval in happy and neutral contexts. However, in the fearful context, the old/new effects were reversed, ERPs were more negative for successful source retrieval compared to correct rejections. Moreover, there were significant emotion effects for

  8. Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

    PubMed

    Barzegar, Marzieh; Sajjadi, Fatemeh Sadat; Talaei, Sayyed Alireza; Hamidi, Gholamali; Salami, Mahmoud

    2015-02-01

    Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals.

  9. Experimental Single-Session Imagery Rescripting of Distressing Memories in Bowel/Bladder-Control Anxiety: A Case Series

    PubMed Central

    Pajak, Rosanna; Kamboj, Sunjeev K.

    2014-01-01

    Bowel and bladder obsession [bowel/bladder-control anxiety (BBCA)] is a viscerally centered phobic syndrome involving a specific concern about losing control of bowel or bladder functioning in a public place. Like other anxiety disorders, BBCA is characterized by intrusive imagery. We have previously described the nature of intrusive mental imagery in BBCA and found imagery themes to be linked to actual experiences of loss of control or to “near misses.” A causal role for imagery in symptom maintenance can be inferred by examining the effects of imagery rescripting. Moreover, successful rescripting may point to a potentially efficacious avenue for treatment development. Three cases of imagery rescripting are described here with pre-, post-, and follow-up (1-week) data reported. After rescripting, two participants experienced pronounced reductions in imagery vividness, distress, shame, disgust, and belief conviction. Most importantly, all three participants experienced a reduction in fear-associated bladder and/or bowel sensations. The results support a causal role for mental imagery in bowel-bladder-control anxiety and suggest that rescripting of distressing intrusive memories linked to recurrent images may be a useful avenue for development of cognitive-behavioral treatments of bladder/bowel-control anxiety. PMID:25566101

  10. The Effects of a Brief Acceptance-based Behavior Therapy vs. Traditional Cognitive Behavior Therapy for Public Speaking Anxiety: Differential Effects on Performance and Verbal Working Memory

    NASA Astrophysics Data System (ADS)

    Glassman, Lisa Hayley

    Individuals with public speaking phobia experience fear and avoidance that can cause extreme distress, impaired speaking performance, and associated problems in psychosocial functioning. Most extant interventions for public speaking phobia focus on the reduction of anxiety and avoidance, but neglect performance. Additionally, very little is known about the relationship between verbal working memory and social performance under conditions of high anxiety. The current study compared the efficacy of two cognitive behavioral treatments, traditional Cognitive Behavioral Therapy (tCBT) and acceptance-based behavior therapy (ABBT), in enhancing public speaking performance via coping with anxiety. Verbal working memory performance, as measured by the backwards digit span (BDS), was measured to explore the relationships between treatment type, anxiety, performance, and verbal working memory. We randomized 30 individuals with high public speaking anxiety to a 90-minute ABBT or tCBT intervention. As this pilot study was underpowered, results are examined in terms of effect sizes as well as statistical significance. Assessments took place at pre and post-intervention and included self-rated and objective anxiety measurements, a behavioral assessment, ABBT and tCBT process measures, and backwards digit span verbal working memory tests. In order to examine verbal working memory during different levels of anxiety and performance pressure, we gave each participant a backwards digit span task three times during each assessment: once under calm conditions, then again while experiencing anticipatory anxiety, and finally under conditions of acute social performance anxiety in front of an audience. Participants were asked to give a video-recorded speech in front of the audience at pre- and post-intervention to examine speech performance. Results indicated that all participants experienced a very large and statistically significant decrease in anxiety (both during the speech and BDS

  11. Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions.

    PubMed

    Hescham, Sarah; Jahanshahi, Ali; Meriaux, Céline; Lim, Lee Wei; Blokland, Arjan; Temel, Yasin

    2015-10-01

    Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex.

  12. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    PubMed Central

    Ménard, Caroline; Quirion, Rémi; Bouchard, Sylvain; Ferland, Guylaine; Gaudreau, Pierrette

    2014-01-01

    The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6–42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats. PMID

  13. Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment

    PubMed Central

    Rudenko, Andrii; Seo, Jinsoo; Hu, Ji; Su, Susan C.; de Anda, Froylan Calderon; Durak, Omer; Ericsson, Maria; Carlén, Marie

    2015-01-01

    Perturbations in fast-spiking parvalbumin (PV) interneurons are hypothesized to be a major component of various neuropsychiatric disorders; however, the mechanisms regulating PV interneurons remain mostly unknown. Recently, cyclin-dependent kinase 5 (Cdk5) has been shown to function as a major regulator of synaptic plasticity. Here, we demonstrate that genetic ablation of Cdk5 in PV interneurons in mouse brain leads to an increase in GABAergic neurotransmission and impaired synaptic plasticity. PVCre;fCdk5 mice display a range of behavioral abnormalities, including decreased anxiety and memory impairment. Our results reveal a central role of Cdk5 expressed in PV interneurons in gating inhibitory neurotransmission and underscore the importance of such regulation during behavioral tasks. Our findings suggest that Cdk5 can be considered a promising therapeutic target in a variety of conditions attributed to inhibitory interneuronal dysfunction, such as epilepsy, anxiety disorders, and schizophrenia. PMID:25673832

  14. Brain Activation Patterns Associated with the Effects of Emotional Distracters during Working Memory Maintenance in Patients with Generalized Anxiety Disorder.

    PubMed

    Park, Jong-Il; Kim, Gwang-Won; Jeong, Gwang-Woo; Chung, Gyung Ho; Yang, Jong-Chul

    2016-01-01

    Few studies have assessed the neural mechanisms of the effects of emotion on cognition in generalized anxiety disorder (GAD) patients. In this functional MRI (fMRI), we investigated the effects of emotional interference on working memory (WM) maintenance in GAD patients. Fifteen patients with GAD participated in this study. Event-related fMRI data were obtained while the participants performed a WM task (face recognition) with neutral and anxiety-provoking distracters. The GAD patients showed impaired performance in WM task during emotional distracters and showed greater activation on brain regions such as DLPFC, VLPFC, amygdala, hippocampus which are responsible for the active maintenance of goal relevant information in WM and emotional processing. Although our results are not conclusive, our finding cautiously suggests the cognitive-affective interaction in GAD patients which shown interfering effect of emotional distracters on WM maintenance.

  15. Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.

    PubMed

    André, Caroline; Dinel, Anne-Laure; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2014-10-01

    Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. Excessive production of proinflammatory cytokines and the resulting activation of the brain tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote neurobehavioral complications, particularly depression. In that context, questions arise about the impact of diet-induced obesity on the onset of neuropsychiatric alterations and the increased susceptibility to immune-mediated diseases displayed by obese patients, particularly through brain IDO activation. To answer these questions, we used C57Bl/6 mice exposed to standard diet or western diet (WD; consisting of palatable energy-dense food) since weaning and for 20 weeks. We then measured inflammatory and behavioral responses to a systemic immune challenge with lipopolysaccharide (LPS) in experimental conditions known to alter cognitive and emotional behaviors independently of any motor impairment. We first showed that in absence of LPS, 9 weeks of WD is sufficient to impair spatial recognition memory (in the Y-maze). On the other hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze), but did not affect depressive-like behavior (in the tail-suspension and forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated

  16. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala.

    PubMed

    Monsey, Melissa S; Ota, Kristie T; Akingbade, Irene F; Hong, Ellie S; Schafe, Glenn E

    2011-01-01

    Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.

  17. Cyclic AMP pathway modifies memory through neural cell adhesion molecule alterations in the rat hippocampus.

    PubMed

    Razmi, Ali; Sahebgharani, Mousa; Khani, Mohammad Hossein; Paylakhi, Seyed Hassan; Faizi, Mehrdad; Zarrindast, Mohammad-Reza

    2014-01-01

    Neural Cell Adhesion Molecules (NCAMs) are known to influence memory by affecting neural cell-cell and cell-extracellular matrix junctions. This study investigated the possible role of cAMP pathway in the expression of hippocampal NCAM and its polysialylated derivative (PSA-NCAM). The following pharmacological tools were employed for manipulation of cAMP pathway: a) forskolin; the activator of adenylyl cyclase (AC), b) 8-Br-cAMP; a protein kinase A (PKA) agonist, c) 8-pCPT-2'-O-Me-cAMP; a selective enhancer of exchange protein activated by cAMP (Epac) and d) Rp-cAMP; a PKA inhibitor. Memory acquisition was tested by passive avoidance paradigm after injecting the above compounds for three consecutive days into the CA1 region of dorsal hippocampus of rats. Forskolin and 8-Br-cAMP enhanced memory retrieval while Rp-cAMP significantly reduced memory and NCAM levels. 8-pCPT-2'-O-Me-cAMP failed to alter memory performance or NCAM levels as compared to vehicle. We observed no significant changes in PSA-NCAM, however the expression of St8sia4 and St8sia2 (the polysialyltransferase isoforms) were altered. The mRNA levels of St8sia4 was down-regulated by 8-Br-cAMP, Rp-cAMP and 8-pCPT while forskolin led to almost 3 and 5 fold increase in mRNAs of St8sia2 and St8sia4, respectively. The current insight might endorse the predominant role of PKA as compared to Epac in cAMP pathway in expression of NCAM and memory function. PMID:24901853

  18. Cronobacter sakazakii infection alters serotonin transporter and improved fear memory retention in the rat.

    PubMed

    Sivamaruthi, Bhagavathi S; Madhumita, Rajkumar; Balamurugan, Krishnaswamy; Rajan, Koilmani E

    2015-01-01

    It is well established that Cronobacter sakazakii infection cause septicemia, necrotizing enterocolitis and meningitis. In the present study, we tested whether the C. sakazakii infection alter the learning and memory through serotonin transporter (SERT). To investigate the possible effect on SERT, on postnatal day-15 (PND-15), wistar rat pups were administered with single dose of C. sakazakii culture (infected group; 10(7) CFU) or 100 μL of Luria-Bertani broth (medium control) or without any treatment (naïve control). All the individuals were subjected to passive avoidance test on PND-30 to test their fear memory. We show that single dose of C. sakazakii infection improved fear memory retention. Subsequently, we show that C. sakazakii infection induced the activation of toll-like receptor-3 and heat-shock proteins-90 (Hsp-90). On the other hand, level of serotonin (5-hydroxytryptamine) and SERT protein was down-regulated. Furthermore, we show that C. sakazakii infection up-regulate microRNA-16 (miR-16) expression. The observed results highlight that C. sakazakii infections was responsible for improved fear memory retention and may have reduced the level of SERT protein, which is possibly associated with the interaction of up-regulated Hsp-90 with SERT protein or miR-16 with SERT mRNA. Taken together, observed results suggest that C. sakazakii infection alter the fear memory possibly through SERT. Hence, this model may be effective to test the C. sakazakii infection induced changes in synaptic plasticity through SERT and effect of other pharmacological agents against pathogen induced memory disorder. PMID:26388777

  19. Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization

    PubMed Central

    Linsenbardt, David N.; Lapish, Christopher C.

    2015-01-01

    Rationale Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. Objectives The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. Methods Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. Results Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. Conclusions The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization. PMID:25572530

  20. Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

    PubMed

    Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

    2013-03-01

    Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

  1. Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse.

    PubMed

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-11-01

    In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central nucleus of the amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BnST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  2. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    PubMed Central

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  3. Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse.

    PubMed

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-11-01

    In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central nucleus of the amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BnST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST.

  4. Self-guides, autobiographical memory, and anxiety and dysphoria: toward a cognitive model of vulnerability to emotional distress.

    PubMed

    Strauman, T J

    1992-02-01

    Several aspects of a cognitive model of vulnerability to emotional disorders based on self-discrepancy theory were tested. Anxious, dysphoric, anxious/dysphoric, and control subjects participated in 3 studies over a 4-month period: screening, assessment of self-guides and self-discrepancies, and an autobiographical memory task in which different types of retrieval cues (including self-guides) were presented and subjects reported childhood memories as they came to mind. Actual:ideal discrepancy was associated with persistent dysphoria, whereas actual:ought discrepancy was associated with persistent anxiety. Self-guide cues resulted in more efficient retrieval and greater unintended negative emotional content than comparable cue types. The groups were differentiated only by negative affect content in response to self-guide cues.

  5. Reduced Anxiety-Like Behavior and Altered Hippocampal Morphology in Female p75NTR(exon IV-/-) Mice.

    PubMed

    Puschban, Zoe; Sah, Anupam; Grutsch, Isabella; Singewald, Nicolas; Dechant, Georg

    2016-01-01

    The presence of the p75 neurotrophin receptor (p75NTR) in adult basal forebrain cholinergic neurons, precursor cells in the subventricular cell layer and the subgranular cell layer of the hippocampus has been linked to alterations in learning as well as anxiety- and depression- related behaviors. In contrast to previous studies performed in a p75NTR(exon III-/-) model still expressing the short isoform of the p75NTR, we focused on locomotor and anxiety-associated behavior in p75NTR(exon IV-/-) mice lacking both p75NTR isoforms. Comparing p75NTR(exon IV-/-) and wildtype mice for both male and female animals showed an anxiolytic-like behavior as evidenced by increased central activities in the open field paradigm and flex field activity system as well as higher numbers of open arm entries in the elevated plus maze test in female p75NTR knockout mice. Morphometrical analyses of dorsal and ventral hippocampus revealed a reduction of width of the dentate gyrus and the granular cell layer in the dorsal but not ventral hippocampus in male and female p75NTR(exon IV-/-) mice. We conclude that germ-line deletion of p75NTR seems to differentially affect morphometry of dorsal and ventral dentate gyrus and that p75NTR may play a role in anxiety-like behavior, specifically in female mice. PMID:27313517

  6. Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

    PubMed Central

    Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

    2016-01-01

    The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

  7. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    PubMed Central

    Mantua, Janna; Mahan, Keenan M.; Henry, Owen S.; Spencer, Rebecca M. C.

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18–22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451

  8. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition

    PubMed Central

    2014-01-01

    Background The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise. Results We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition. Conclusions Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy. PMID:25217888

  9. LY293558 prevents soman-induced pathophysiological alterations in the basolateral amygdala and the development of anxiety.

    PubMed

    Prager, Eric M; Figueiredo, Taiza H; Long, Robert P; Aroniadou-Anderjaska, Vassiliki; Apland, James P; Braga, Maria F M

    2015-02-01

    Exposure to nerve agents can cause brain damage due to prolonged seizure activity, producing long-term behavioral deficits. We have previously shown that LY293558, a GluK1/AMPA receptor antagonist, is a very effective anticonvulsant and neuroprotectant against nerve agent exposure. In the present study, we examined whether the protection against nerve agent-induced seizures and neuropathology conferred by LY293558 translates into protection against pathophysiological alterations in the basolateral amygdala (BLA) and the development of anxiety, which is the most prevalent behavioral deficit resulting from exposure. LY293558 (15 mg/kg) was administered to rats, along with atropine and HI-6, at 20 min after exposure to soman (1.2 × LD50). At 24 h, 7 days, and 30 days after exposure, soman-exposed rats who did not receive LY293558 had reduced but prolonged evoked field potentials in the BLA, as well as increased paired-pulse ratio, suggesting neuronal damage and impaired synaptic inhibition; rats who received LY293558 did not differ from controls in these parameters. Long-term potentiation of synaptic transmission was impaired at 7 days after exposure in the soman-exposed rats who did not receive anticonvulsant treatment, but not in the LY293558-treated rats. Anxiety-like behavior assessed by the open field and acoustic startle response tests was increased in the soman-exposed rats at 30 and 90 days after exposure, while rats treated with LY293558 did not differ from controls. Along with our previous findings, the present data demonstrate the remarkable efficacy of LY293558 in counteracting nerve agent-induced seizures, neuropathology, pathophysiological alterations in the BLA, and anxiety-related behavioral deficits.

  10. Choke or thrive? The relation between salivary cortisol and math performance depends on individual differences in working memory and math-anxiety.

    PubMed

    Mattarella-Micke, Andrew; Mateo, Jill; Kozak, Megan N; Foster, Katherine; Beilock, Sian L

    2011-08-01

    In the current study, we explored how a person's physiological arousal relates to their performance in a challenging math situation as a function of individual differences in working memory (WM) capacity and math-anxiety. Participants completed demanding math problems before and after which salivary cortisol, an index of arousal, was measured. The performance of lower WM individuals did not depend on cortisol concentration or math-anxiety. For higher WM individuals high in math-anxiety, the higher their concentration of salivary cortisol following the math task, the worse their performance. In contrast, for higher WM individuals lower in math-anxiety, the higher their salivary cortisol concentrations, the better their performance. For individuals who have the capacity to perform at a high-level (higher WMs), whether physiological arousal will lead an individual to choke or thrive depends on math-anxiety.

  11. Grape powder supplementation prevents oxidative stress-induced anxiety-like behavior, memory impairment, and high blood pressure in rats.

    PubMed

    Allam, Farida; Dao, An T; Chugh, Gaurav; Bohat, Ritu; Jafri, Faizan; Patki, Gaurav; Mowrey, Christopher; Asghar, Mohammad; Alkadhi, Karim A; Salim, Samina

    2013-06-01

    We examined whether or not grape powder treatment ameliorates oxidative stress-induced anxiety-like behavior, memory impairment, and hypertension in rats. Oxidative stress in Sprague-Dawley rats was produced by using L-buthionine-(S,R)-sulfoximine (BSO). Four groups of rats were used: 1) control (C; injected with vehicle and provided with tap water), 2) grape powder-treated (GP; injected with vehicle and provided for 3 wk with 15 g/L grape powder dissolved in tap water), 3) BSO-treated [injected with BSO (300 mg/kg body weight), i.p. for 7 d and provided with tap water], and 4) BSO plus grape powder-treated (GP+BSO; injected with BSO and provided with grape powder-treated tap water). Anxiety-like behavior was significantly greater in BSO rats compared with C or GP rats (P < 0.05). Grape powder attenuated BSO-induced anxiety-like behavior in GP+BSO rats. BSO rats made significantly more errors in both short- and long-term memory tests compared with C or GP rats (P < 0.05), which was prevented in GP+BSO rats. Systolic and diastolic blood pressure was significantly greater in BSO rats compared with C or GP rats (P < 0.05), whereas grape powder prevented high blood pressure in GP+BSO rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK-1/2) was activated (P < 0.05), whereas levels of glyoxalase-1 (GLO-1), glutathione reductase-1 (GSR-1), calcium/calmodulin-dependent protein kinase type IV (CAMK-IV), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were significantly less (P < 0.05) in BSO but not in GP+BSO rats compared with C or GP rats. We suggest that by regulating brain ERK-1/2, GLO-1, GSR-1, CAMK-IV, CREB, and BDNF levels, grape powder prevents oxidative stress-induced anxiety, memory impairment, and hypertension in rats. PMID:23596160

  12. The effect of pitch, rhythm, and familiarity on working memory and anxiety as measured by digit recall performance.

    PubMed

    Silverman, Michael J

    2010-01-01

    The purpose of this study was to isolate and quantitatively evaluate the effects of pitch and rhythm of unfamiliar and familiar melodies on working memory and anxiety as measured by sequential digit recall performance. Participants (N = 60) listened to 6 treatment conditions each consisting of 9 randomized monosyllabic digits. The digits were paired with (a) a familiar melody and pitch only, (b) a familiar melody and rhythm only, (c) a familiar melody with both pitch and rhythm, (d) an unfamiliar melody with pitch only, (e) an unfamiliar melody with rhythm only, and (f) an unfamiliar melody with both pitch and rhythm. The 6 different treatments were counterbalanced using a Latin square design in an attempt to control for order effects. Participants rated their state anxiety on a Likert-type scale before, midway through, and after the digits test. No statistically significant order, learning, or practice effects were found. A 3-way repeated-measures ANOVA indicated a statistically significant difference in digit recall performance across musical element conditions and groups. Results indicated that music majors outperformed nonmusic majors on the digit recall task. Participants were able to recall digits from the rhythm condition most accurately while recalling digits from pitch only and both pitch and rhythm conditions the least accurately. Graphic analysis of treatment as a function of sequential position indicated digit recall was best during conditions of primacy and recency. No main effects were found for the familiarity condition. Additionally, no main effects or interactions were found for the anxiety variable. The results of this study are congruent with existing working memory and music literature suggesting that pairing information with rhythm can facilitate recall, music majors outperform non-music majors, and recall accuracy is best in positions of primacy and recency. Implications for practice in therapy and education are made as well as suggestions for

  13. The effect of pitch, rhythm, and familiarity on working memory and anxiety as measured by digit recall performance.

    PubMed

    Silverman, Michael J

    2010-01-01

    The purpose of this study was to isolate and quantitatively evaluate the effects of pitch and rhythm of unfamiliar and familiar melodies on working memory and anxiety as measured by sequential digit recall performance. Participants (N = 60) listened to 6 treatment conditions each consisting of 9 randomized monosyllabic digits. The digits were paired with (a) a familiar melody and pitch only, (b) a familiar melody and rhythm only, (c) a familiar melody with both pitch and rhythm, (d) an unfamiliar melody with pitch only, (e) an unfamiliar melody with rhythm only, and (f) an unfamiliar melody with both pitch and rhythm. The 6 different treatments were counterbalanced using a Latin square design in an attempt to control for order effects. Participants rated their state anxiety on a Likert-type scale before, midway through, and after the digits test. No statistically significant order, learning, or practice effects were found. A 3-way repeated-measures ANOVA indicated a statistically significant difference in digit recall performance across musical element conditions and groups. Results indicated that music majors outperformed nonmusic majors on the digit recall task. Participants were able to recall digits from the rhythm condition most accurately while recalling digits from pitch only and both pitch and rhythm conditions the least accurately. Graphic analysis of treatment as a function of sequential position indicated digit recall was best during conditions of primacy and recency. No main effects were found for the familiarity condition. Additionally, no main effects or interactions were found for the anxiety variable. The results of this study are congruent with existing working memory and music literature suggesting that pairing information with rhythm can facilitate recall, music majors outperform non-music majors, and recall accuracy is best in positions of primacy and recency. Implications for practice in therapy and education are made as well as suggestions for

  14. Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice

    PubMed Central

    Bedrosian, Tracy A.; Herring, Kamillya L.; Weil, Zachary M.; Nelson, Randy J.

    2011-01-01

    Both normal aging and dementia are associated with dysregulation of the biological clock, which contributes to disrupted circadian organization of physiology and behavior. Diminished circadian organization in conjunction with the loss of cholinergic input to the cortex likely contributes to impaired cognition and behavior. One especially notable and relatively common circadian disturbance among the aged is “sundowning syndrome,” which is characterized by exacerbated anxiety, agitation, locomotor activity, and delirium during the hours before bedtime. Sundowning has been reported in both dementia patients and cognitively intact elderly individuals living in institutions; however, little is known about temporal patterns in anxiety and agitation, and the neurobiological basis of these rhythms remains unspecified. In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice. We then attempted to treat the observed behavioral disturbances in the aged mice using chronic nightly melatonin treatment. Finally, we tested the hypothesis that time-of-day differences in acetylcholinesterase and choline acetyltransferase expression and general neuronal activation (i.e., c-Fos expression) coincide with the behavioral symptoms. Our results show a temporal pattern of anxiety-like behavior that emerges in elderly mice. This behavioral pattern coincides with elevated locomotor activity relative to adult mice near the end of the dark phase, and with time-dependent changes in basal forebrain acetylcholinesterase expression. Transgenic APP mice show a similar behavioral phenomenon that is not observed among age-matched wild-type mice. These results may have useful applications to the study and treatment of age- and dementia-related circadian behavioral disturbances, namely, sundowning syndrome. PMID:21709248

  15. Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice

    PubMed Central

    Chris Ajonijebu, Duyilemi; Adeyemi Adeniyi, Philip; Oloruntoba Adekeye, Adeshina; Peter Olatunji, Babawale; Olakunle Ishola, Azeez; Michael Ogundele, Olalekan

    2014-01-01

    In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca2+ concentration and had no significant effect on K+ ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd2+ in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety. PMID:26317007

  16. Examination of spatial working memory performance in children and adolescents with attention deficit hyperactivity disorder, combined type (ADHD-CT) and anxiety.

    PubMed

    Vance, Alasdair; Ferrin, Maite; Winther, Jo; Gomez, Rapson

    2013-08-01

    Spatial working memory (SWM) is known to be impaired in children with ADHD-CT, whether anxiety is present or not. Yet, it remains unclear whether anxiety disorders add to the SWM impairments evident in ADHD-CT and whether these findings extend into adolescents with ADHD-CT and anxiety. Further, it is not yet known whether children and adolescents with carefully defined anxiety disorders alone, demonstrate SWM deficits. This study explored the association of SWM and its strategy and spatial span components in carefully defined children and adolescents (age 6-16 years) with ADHD-CT alone (N = 163; 14 % female), ADHD-CT and anxiety (N = 243; 23 % female), anxiety disorders alone (N = 69; 25 % female) compared to age- and gender-matched healthy control participants (N = 116; 19 % female). The relationship between SWM and its strategy and span components and core ADHD-CT symptoms and anxiety symptoms were also examined. There was no evidence of an additive effect of ADHD and anxiety on SWM, strategy and spatial span deficits. But, anxiety disorders alone were associated with impaired SWM and span performance compared to healthy control participants. In contrast, strategy did not differ between children and adolescents with anxiety disorders alone and healthy control participants, suggesting that with anxiety span is the most affected component. Further, these findings were age-independent. This study concurs with and extends current influential models about the cognitive effects of anxiety on performance in the setting of ADHD-CT. Clinical implications and future research directions are discussed.

  17. Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

    PubMed Central

    Yang, Su-Rong; Sun, Hui; Huang, Zhi-Li; Yao, Ming-Hui; Qu, Wei-Min

    2012-01-01

    Study Objectives: To investigate possible differences in the effect of repeated sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and spatial learning and memory ability. Design: The authors examined electroencephalograms of rats as they were subjected to 4-h daily sleep deprivation that continued for 7 consecutive days and assessed the spatial learning and memory by Morris water maze test (WMT). Participants: Adolescent and adult rats. Measurements and Results: Adolescent rats exhibited a similar amount of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with prolonged durations, indicating they have better sleep quality than adult rats. After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7 h, respectively. Furthermore, the authors investigated the effects of 4-h daily sleep deprivation immediately after the water maze training sessions on spatial cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a longer distance to find the hidden platform during the acquisition training and had fewer numbers of platform crossings in the probe trial than those in the control group, something that did not occur in the sleep-deprived adult rats. Conclusions: Repeated sleep restriction (RSR) altered sleep profiles and mildly impaired spatial learning and memory capability in adolescent rats. Citation: Yang SR; Sun H; Huang ZL; Yao MH; Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. SLEEP 2012;35(6):849-859. PMID:22654204

  18. Functional Alterations in Order Short-Term Memory Networks in Adults With Dyslexia.

    PubMed

    Martinez Perez, Trecy; Poncelet, Martine; Salmon, Eric; Majerus, Steve

    2015-01-01

    Dyslexia is characterized not only by reading impairment but also by short-term memory (STM) deficits, and this particularly for the retention of serial order information. Here, we explored the functional neural correlates associated with serial order STM performance of adults with dyslexia for verbal and visual STM tasks. Relative to a group of age-matched controls, the dyslexic group showed abnormal activation in a network associated with order STM encompassing the right intraparietal and superior frontal sulcus, and this for both verbal and visual order STM conditions. This study highlights long-lasting alterations in non-language neural substrates and processes in dyslexia. PMID:27043828

  19. Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission

    PubMed Central

    Albrecht, David; Lomoio, Selene; Haydon, Philip G.; Moss, Stephen J.; Tesco, Giuseppina

    2016-01-01

    Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer’s disease (AD)-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates. PMID:27192432

  20. Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission.

    PubMed

    Walker, Kendall R; Modgil, Amit; Albrecht, David; Lomoio, Selene; Haydon, Philip G; Moss, Stephen J; Tesco, Giuseppina

    2016-01-01

    Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer's disease (AD)-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates. PMID:27192432

  1. Overexpression of mineralocorticoid receptors does not affect memory and anxiety-like behavior in female mice

    PubMed Central

    Kanatsou, Sofia; Kuil, Laura E.; Arp, Marit; Oitzl, Melly S.; Harris, Anjanette P.; Seckl, Jonathan R.; Krugers, Harm J.; Joels, Marian

    2015-01-01

    Mineralocorticoid receptors (MRs) have been implicated in behavioral adaptation and learning and memory. Since—at least in humans—MR function seems to be sex-dependent, we examined the behavioral relevance of MR in female mice exhibiting transgenic MR overexpression in the forebrain. Transgenic MR overexpression did not affect contextual fear memory or cued fear learning and memory. Moreover, MR overexpressing and control mice discriminated equally well between fear responses in a combined cue and context fear conditioning paradigm. Also context-memory in an object recognition task was unaffected in MR overexpressing mice. We conclude that MR overexpression in female animals does not affect fear conditioned responses and object recognition memory. PMID:26236208

  2. High aggression in rats is associated with elevated stress, anxiety-like behavior, and altered catecholamine content in the brain.

    PubMed

    Patki, Gaurav; Atrooz, Fatin; Alkadhi, Isam; Solanki, Naimesh; Salim, Samina

    2015-01-01

    The social defeat paradigm involves aggressive encounters between Long-Evans (L-E) (resident) and Sprague-Dawley (S-D) (intruder) rats. Successful application of chronic social defeat stress in S-D rats is dependent upon selection of highly aggressive L-E rats. Half of the L-E rats screened for aggression did not meet the criterion for aggression (L-E rats performing a defeat, characterized by the intruder surrendering or acquiring a supine position for at least 3s). The observation of the differences in the level of aggression between age and weight matched L-E rats was quite compelling which led us to the present study. Herein, we measured behavioral differences between aggressor and non-aggressor L-E rats. We analyzed their anxiety-like behavior using open-field and elevated plus maze tests. We also measured aggression/violence-like behavior using two tests. In one, time taken to defeat the intruder S-D rat was recorded. In the second test, time taken to attack a novel object was compared between the two groups. We observed a significant increase in anxiety-like behavior in aggressor rats when compared to the non-aggressive group. Furthermore, time taken to defeat the intruder rat and to attack a novel object was significantly lower in aggressive L-E rats. Biochemical data suggests that heightened anxiety-like behavior and aggression is associated with increased plasma levels of corticosterones and elevated oxidative stress. Significant alterations in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) were observed within the hippocampus, amygdala, and the prefrontal cortex, suggesting potential involvement of dopaminergic and noradrenergic systems in regulation of aggressive behaviors.

  3. Effects of imperatorin on nicotine-induced anxiety- and memory-related responses and oxidative stress in mice.

    PubMed

    Budzynska, Barbara; Boguszewska-Czubara, Anna; Kruk-Slomka, Marta; Skalicka-Wozniak, Krystyna; Michalak, Agnieszka; Musik, Irena; Biala, Grazyna; Glowniak, Kazimierz

    2013-10-01

    The purpose of the reported experiments was to examine the effects of imperatorin [9-[(3-methylbut-2-en-1-yl)oxy]-7H-furo[3,2-g]chromen-7-one] on anxiety and memory-related responses induced by nicotine in mice and their relation to the level of nicotine-induced oxidative stress in brain as well as in the hippocampus and the prefrontal cortex. Male Swiss mice were tested for anxiety in the elevated plus maze test (EPM), and for cognition using passive avoidance (PA) procedures. Imperatorin, purified by high-speed counter-current chromatography from methanol extract of fruits of Angelica officinalis, acutely administered at the doses of 10 and 20mg/kg impaired the anxiogenic effect of nicotine (0.1mg/kg, s.c.). Furthermore, acute injections of subthreshold dose of imperatorin (1mg/kg, i.p.) improved processes of memory acquisition when co-administered with nicotine used at non-active dose of 0.05 mg/kg, s.c. Additionally, repeated administration of imperatorin (1mg/kg, i.p., twice daily, for 6 days) improved different stages of memory processes (both acquisition and consolidation) when injected in combination with non-active dose of nicotine (0.05 mg/kg, s.c.) in the PA task. Oxidative stress was assessed by determination of antioxidant enzymes (glutathione peroxidases (GPx), superoxide dismutase (SOD), glutathione reductase (GR)) activities as well as of malondialdehyde (MDA) concentration in the whole brain, the hippocampus and the prefrontal cortex after repeated administration of imperatorin (1mg/kg, 6 days) and single nicotine injection (0.05 mg/kgs.c.) on the seventh day. The results of our research suggest strong behavioural interaction between imperatorin and nicotine at the level of anxiety- and cognitive-like processes. Furthermore, imperatorin inhibited nicotine-induced changes in examined indicators of oxidative stress, especially in the hippocampus and the cortex.

  4. ADHD Subtypes and Co-Occurring Anxiety, Depression, and Oppositional-Defiant Disorder: Differences in Gordon Diagnostic System and Wechsler Working Memory and Processing Speed Index Scores

    ERIC Educational Resources Information Center

    Mayes, Susan Dickerson; Calhoun, Susan L.; Chase, Gary A.; Mink, Danielle M.; Stagg, Ryan E.

    2009-01-01

    Objective: Wechsler Intelligence Scale for Children Freedom-from-Distractibility/Working Memory Index (FDI/WMI), Processing Speed Index (PSI), and Gordon Diagnostic System (GDS) scores in ADHD children were examined as a function of subtype and coexisting anxiety, depression, and oppositional-defiant disorder. Method: Participants were 587…

  5. Reduced Anxiety-Like Behavior and Altered Hippocampal Morphology in Female p75NTRexon IV−/− Mice

    PubMed Central

    Puschban, Zoe; Sah, Anupam; Grutsch, Isabella; Singewald, Nicolas; Dechant, Georg

    2016-01-01

    The presence of the p75 neurotrophin receptor (p75NTR) in adult basal forebrain cholinergic neurons, precursor cells in the subventricular cell layer and the subgranular cell layer of the hippocampus has been linked to alterations in learning as well as anxiety- and depression- related behaviors. In contrast to previous studies performed in a p75NTRexon III−/− model still expressing the short isoform of the p75NTR, we focused on locomotor and anxiety–associated behavior in p75NTRexon IV−/− mice lacking both p75NTR isoforms. Comparing p75NTRexon IV−/− and wildtype mice for both male and female animals showed an anxiolytic-like behavior as evidenced by increased central activities in the open field paradigm and flex field activity system as well as higher numbers of open arm entries in the elevated plus maze test in female p75NTR knockout mice. Morphometrical analyses of dorsal and ventral hippocampus revealed a reduction of width of the dentate gyrus and the granular cell layer in the dorsal but not ventral hippocampus in male and female p75NTRexon IV−/− mice. We conclude that germ-line deletion of p75NTR seems to differentially affect morphometry of dorsal and ventral dentate gyrus and that p75NTR may play a role in anxiety-like behavior, specifically in female mice. PMID:27313517

  6. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice

    PubMed Central

    Planagumà, Jesús; Leypoldt, Frank; Mannara, Francesco; Gutiérrez-Cuesta, Javier; Martín-García, Elena; Aguilar, Esther; Titulaer, Maarten J.; Petit-Pedrol, Mar; Jain, Ankit; Balice-Gordon, Rita; Lakadamyali, Melike; Graus, Francesc; Maldonado, Rafael

    2015-01-01

    Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients’ antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients’ antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients’ or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients’ cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal

  7. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice.

    PubMed

    Planagumà, Jesús; Leypoldt, Frank; Mannara, Francesco; Gutiérrez-Cuesta, Javier; Martín-García, Elena; Aguilar, Esther; Titulaer, Maarten J; Petit-Pedrol, Mar; Jain, Ankit; Balice-Gordon, Rita; Lakadamyali, Melike; Graus, Francesc; Maldonado, Rafael; Dalmau, Josep

    2015-01-01

    Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients' antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients' antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients' or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients' cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal on Days

  8. Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation.

    PubMed

    Abercrombie, Heather C; Jahn, Allison L; Davidson, Richard J; Kern, Simone; Kirschbaum, Clemens; Halverson, Jerry

    2011-01-01

    Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.

  9. The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety

    PubMed Central

    Scott, Julia A.; Goodrich-Hunsaker, Naomi; Kalish, Kristopher; Lee, Aaron; Hunsaker, Michael R.; Schumann, Cynthia M.; Carmichael, Owen T.; Simon, Tony J.

    2016-01-01

    Background Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population. Methods We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety. Results We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. Limitations Shape alterations are not specific to hippocampal subfields. Conclusion Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection

  10. Novel mechanistic insights into treadmill exercise based rescue of social defeat-induced anxiety-like behavior and memory impairment in rats.

    PubMed

    Patki, Gaurav; Solanki, Naimesh; Atrooz, Fatin; Ansari, Amber; Allam, Farida; Jannise, Brittany; Maturi, Jaganmohan; Salim, Samina

    2014-05-10

    Social defeat (SD) induced stress causes physiological and behavioral deficits in rodents, including depression and anxiety-like behaviors, as well as memory impairment. Anxiolytic and mood elevating effects of physical exercise are also known. However, rescue effect of physical exercise in social defeat-induced anxiety, depression or memory impairment has not been addressed. The role of epigenetic mechanisms that potentially contribute to these rescue or protective effects is also not known. The present study investigated the effect of moderate treadmill exercise on anxiety-like behavior and memory function in rats subjected to SD using a modified version of the resident-intruder model for social stress (defeat). Changes in histone acetylation and histone-modifying enzymes were examined in hippocampus, amygdala and frontal cortex which are considered critical for anxiety, depression and cognition. Sprague Dawley rats were randomly assigned in four groups; control, exercised, social defeat, social defeat and exercise. At the end of the SD or control exposure lasting 30 min daily for 7 days, one group of SD rats was subjected to treadmill exercise for 2 weeks, whereas the other SD group was handled without exercise. Anxiety-like behavior tests and radial arm water maze test suggested that moderate treadmill exercise rescued social defeat induced anxiety-like behavior and memory impairment. Moreover, exercise normalized SD-induced increase in oxidative stress, most likely by adjusting antioxidant response. Our data suggests involvement of epigenetic mechanisms including histone acetylation of H3 and modulation of methyl-CpG-binding in the hippocampus that might contribute to the rescue effects of exercise in SD-induced behavioral deficits in rats.

  11. Chronic Administration of Benzo(a)pyrene Induces Memory Impairment and Anxiety-Like Behavior and Increases of NR2B DNA Methylation

    PubMed Central

    Zhang, Wenping; Tian, Fengjie; Zheng, Jinping; Li, Senlin; Qiang, Mei

    2016-01-01

    Background Recently, an increasing number of human and animal studies have reported that exposure to benzo(a)pyrene (BaP) induces neurological abnormalities and is also associated with adverse effects, such as tumor formation, immunosuppression, teratogenicity, and hormonal disorders. However, the exact mechanisms underlying BaP-induced impairment of neurological function remain unclear. The aim of this study was to examine the regulating mechanisms underlying the impact of chronic BaP exposure on neurobehavioral performance. Methods C57BL mice received either BaP in different doses (1.0, 2.5, 6.25 mg/kg) or olive oil twice a week for 90 days. Memory and emotional behaviors were evaluated using Y-maze and open-field tests, respectively. Furthermore, levels of mRNA expression were measured by using qPCR, and DNA methylation of NMDA receptor 2B subunit (NR2B) was examined using bisulfate pyrosequencing in the prefrontal cortex and hippocampus. Results Compared to controls, mice that received BaP (2.5, 6.25 mg/kg) showed deficits in short-term memory and an anxiety-like behavior. These behavioral alterations were associated with a down-regulation of the NR2B gene and a concomitant increase in the level of DNA methylation in the NR2B promoter in the two brain regions. Conclusions Chronic BaP exposure induces an increase in DNA methylation in the NR2B gene promoter and down-regulates NR2B expression, which may contribute to its neurotoxic effects on behavioral performance. The results suggest that NR2B vulnerability represents a target for environmental toxicants in the brain. PMID:26901155

  12. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    PubMed Central

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  13. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.

    PubMed

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  14. LY293558 prevents soman-induced pathophysiological alterations in the basolateral amygdala and the development of anxiety

    PubMed Central

    Prager, Eric M.; Figueiredo, Taiza H.; Long, Robert P.; Aroniadou-Anderjaska, Vassiliki; Apland, James P.; Braga, Maria F.M.

    2014-01-01

    Without timely pharmacological treatment, nerve agent exposure can cause a large number of casualties, as occurred in the recent sarin attack in Syria. Nerve agent-induced seizures are initiated due to inhibition of acetylcholinesterase, but they become quickly refractory to muscarinic antagonists, and their suppression by benzodiazepines can be only temporary. Therefore, novel treatments are necessary to stop seizures and prevent brain damage and the resulting long-term behavioral deficits. We have previously shown that LY293558, a GluK1/AMPA receptor antagonist, is a very effective anticonvulsant and neuroprotectant against nerve agent exposure. In the present study, we examined whether the protection against nerve agent-induced seizures and neuropathology conferred by LY293558 translates into protection against pathophysiological alterations in the basolateral amygdala (BLA) and the development of anxiety, which is the most prevalent behavioral deficit resulting from exposure. LY293558 (15 mg/kg) was administered to rats along with atropine and the oxime HI-6, at 20 min after exposure to soman (1.2 x LD50). At 24 h, 7 days, and 30 days after exposure, soman-exposed rats that did not receive LY293558 had reduced but prolonged evoked field potentials in the BLA, as well as increased paired-pulse ratio, suggesting neuronal damage and impaired synaptic inhibition. In contrast, soman-exposed rats that received LY293558 did not differ from controls in these parameters. Similarly, long-term potentiation of synaptic transmission was impaired at 7 days after exposure in the soman-exposed rats that did not receive anticonvulsant treatment, while this impairment was not present in the LY293558-treated rats. Anxiety-like behavior assessed by the open field and acoustic startle response tests was increased in the soman-exposed rats at 30 and 90 days after exposure, while soman-exposed rats treated with LY293558 did not differ from controls. Along with our previous findings

  15. Altering Test Environments for Reducing Test Anxiety and for Improving Academic Performance.

    ERIC Educational Resources Information Center

    Bushnell, Don D.

    To test the effects of altering situational variables in stressful examinations on high test anxious and low test anxious undergraduates, mid-terms and final examinations were administered in two environmental settings: large lecture halls and small language laboratories. Mean test scores for high test anxious students in the language labs were…

  16. Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

    PubMed Central

    Varga, Dániel; Herédi, Judit; Kánvási, Zita; Ruszka, Marian; Kis, Zsolt; Ono, Etsuro; Iwamori, Naoki; Iwamori, Tokuko; Takakuwa, Hiroki; Vécsei, László; Toldi, József; Gellért, Levente

    2015-01-01

    L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice. PMID:26136670

  17. Grape Powder Intake Prevents Ovariectomy-Induced Anxiety-Like Behavior, Memory Impairment and High Blood Pressure in Female Wistar Rats

    PubMed Central

    Patki, Gaurav; Allam, Farida H.; Atrooz, Fatin; Dao, An T.; Solanki, Naimesh; Chugh, Gaurav; Asghar, Mohammad; Jafri, Faizan; Bohat, Ritu; Alkadhi, Karim A.; Salim, Samina

    2013-01-01

    Diminished estrogen influence at menopause is reported to be associated with cognitive decline, heightened anxiety and hypertension. While estrogen therapy is often prescribed to overcome these behavioral and physiological deficits, antioxidants which have been shown beneficial are gaining nutritional intervention and popularity. Therefore, in the present study, utilizing the antioxidant properties of grapes, we have examined effect of 3 weeks of grape powder (GP; 15 g/L dissolved in tap water) treatment on anxiety-like behavior, learning-memory impairment and high blood pressure in ovariectomized (OVX) rats. Four groups of female Wistar rats were used; sham control, sham-GP treated, OVX and OVX+GP treated. We observed a significant increase in systolic and diastolic blood pressure in OVX rats as compared to sham-controls. Furthermore, ovariectomy increased anxiety-like behavior and caused learning and memory impairment in rats as compared to sham-controls. Interestingly, providing grape powder treated water to OVX rats restored both systolic and diastolic blood pressure, decreased anxiety-like behavior and improved memory function. Moreover, OVX rats exhibited an impaired long term potentiation which was restored with grape powder treatment. Furthermore, ovariectomy increased oxidative stress in the brain, serum and urine, selectively decreasing antioxidant enzyme, glyoxalase-1 protein expression in the hippocampus but not in the cortex and amygdala of OVX rats, while grape powder treatment reversed these effects. Other antioxidant enzyme levels, including manganese superoxide dismutase (SOD) and Cu/Zn SOD remained unchanged. We suggest that grape powder by regulating oxidative stress mechanisms exerts its protective effect on blood pressure, learning-memory and anxiety-like behavior. Our study is the first to examine behavioral, biochemical, physiological and electrophysiological outcome of estrogen depletion in rats and to test protective role of grape powder

  18. Altered outward K(+) currents in Drosophila larval neurons of memory mutants rutabaga and amnesiac.

    PubMed

    Yu, D; Feng, C; Guo, A

    1999-08-01

    K(+) currents in cultured Drosophila larval neurons have been classified into four categories according to their inactivation time constants, relative amplitude, and response to K(+) channel blockers 4-AP and tetraethylammonium. The percentage (65%) of neurons displaying K(+) currents which were reduced to 30% in amplitude by 5 mM cyclic adenosine monophosphate (cAMP) analog 8-bromo-cAMP in both Drosophila memory mutants rutabaga (rut) and amnesiac (amn) was significantly larger than that (50%) in wild type. This initial characterization provides evidence for altered K(+) currents in both rut and amn mutants. Arachidonic acid, a specifical inhibitor of Kv4 family (shal) K(+) channels, was found to inhibit K(+) currents in cultured Drosophila neurons, suggesting the presence of shal channels in these neurons. PMID:10413447

  19. The Effects of Emotional Memory Skills on Public Speaking Anxiety: A First Look.

    ERIC Educational Resources Information Center

    Holtz, James; Reynolds, Gayla

    This paper focuses on the use of emotional memory skills to reduce communication apprehension, pioneered as a new cognitive intervention treatment called "The Imaging System for Public Speaking" (Keaten et al, 1994). The paper briefly explains other cognitive intervention strategies commonly used, including rational-emotive therapy, visualization,…

  20. Working Memory Deficits, Increased Anxiety-Like Traits, and Seizure Susceptibility in BDNF Overexpressing Mice

    ERIC Educational Resources Information Center

    Papaleo, Francesco; Silverman, Jill L.; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L.; Chadman, Kathryn K.; Crawley, Jacqueline N.

    2011-01-01

    BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher…

  1. Working memory network alterations and associated symptoms in adults with ADHD and Bipolar Disorder

    PubMed Central

    Brown, Ariel; Biederman, Joseph; Valera, Eve; Lomedico, Alexandra; Aleardi, Megan; Makris, Nikos; Seidman, Larry J.

    2012-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, however underlying neural circuitry contributing to the comorbidity remain understudied. Our aim was to investigate functional brain circuitry during working memory in a group of participants who meet criteria for both disorders (ADHD+BPD), and to explore the relationship of symptoms of each disorder to brain function. We used fMRI to image brain activity in 18 male adults with both ADHD and BPD, and 18 healthy control participants matched one-to-one on age, sex, and handedness, while they performed a sequential letter n-back task. We investigated differences in activation between these groups, and also correlations of brain activity during the task to symptoms of ADHD and BPD independently. We found significant hypoactivity in the subjects with ADHD+BPD vs. controls across frontal and parietal regions, and further, found that BPD and ADHD symptoms related to activity in anatomically distinct regions that were respectively characterized by activation and suppression during task. We conclude that comorbid ADHD+BPD is associated with alterations across anterior and posterior nodes of the working memory network, and symptoms of each disorder are related to anatomically and functionally distinct brain regions. PMID:22272986

  2. Altered emotionality, spatial memory and cholinergic function in caveolin-1 knock-out mice.

    PubMed

    Gioiosa, Laura; Raggi, Carla; Ricceri, Laura; Jasmin, Jean-François; Frank, Philippe G; Capozza, Franco; Lisanti, Michael P; Alleva, Enrico; Sargiacomo, Massimo; Laviola, Giovanni

    2008-04-01

    Neurological phenotypes associated with loss of caveolin 1 (cav-1) (the defining structural protein in caveolar vesicles, which regulate signal transduction and cholesterol trafficking in cells) in mice have been reported recently. In brain, cav-1 is highly expressed in neurons and glia. We investigated emotional and cognitive behavioural domains in mice deficient in cav-1 (CavKO mice). CavKO mice were more anxious and spent more time in self-directed grooming behaviour than wild-type (wt) mice. In a spatial/working memory task, CavKO mice failed to recognize the object displacement, thus showing a spatial memory impairment. CavKO mice showed higher locomotor activity than wt mice, thus suggesting reduced inhibitory function by CNS cholinergic systems. Behavioural response to the cholinergic muscarinic antagonist, scopolamine (2 mg/Kg), was decreased in CavKO mice. Few behavioural sex differences emerged in mice; whereas the sex differences were generally attenuated or even reverted in the null genotype. Our data confirm a distinct behavioural phenotype in CavKO mice and indicate a selective alteration in central cholinergic function.

  3. Hippocampus-based contextual memory alters the morphological characteristics of astrocytes in the dentate gyrus.

    PubMed

    Choi, Moonseok; Ahn, Sangzin; Yang, Eun-Jeong; Kim, Hyunju; Chong, Young Hae; Kim, Hye-Sun

    2016-07-26

    Astrocytes have been reported to exist in two states, the resting and the reactive states. Morphological changes in the reactive state of astrocytes include an increase in thickness and number of processes, and an increase in the size of the cell body. Molecular changes also occur, such as an increase in the expression of glial fibrillary acidic protein (GFAP). However, the morphological and molecular changes during the process of learning and memory have not been elucidated. In the current study, we subjected Fvb/n mice to contextual fear conditioning, and checked for morphological and molecular changes in astrocytes. 1 h after fear conditioning, type II and type III astrocytes exhibited a unique status with an increased number of processes and decreased GFAP expression which differed from the typical resting or reactive state. In addition, the protein level of excitatory excitatory amino acid transporter 2 (EAAT2) was increased 1 h to 24 h after contextual fear conditioning while EAAT1 did not show any alterations. Connexin 43 (Cx43) protein was found to be increased at 24 h after fear conditioning. These data suggest that hippocampus-based contextual memory process induces changes in the status of astrocytes towards a novel status different from typical resting or reactive states. These morphological and molecular changes may be in line with functional changes.

  4. Neonatal Perirhinal Lesions in Rhesus Macaques Alter Performance on Working Memory Tasks with High Proactive Interference

    PubMed Central

    Weiss, Alison R.; Nadji, Ryhan; Bachevalier, Jocelyne

    2016-01-01

    The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but

  5. Pre- and postnatal dietary protein deficiency influences anxiety, memory and social behaviour in the African striped mouse Rhabdomys dilectus chakae.

    PubMed

    Pillay, Neville; Rimbach, Rebecca; Rymer, Tasmin

    2016-07-01

    Dietary protein deficiency influences the behavioural phenotypes of mammals. We studied whether protein deficiency during gestation and/or post-weaning heightened anxiety, reduced memory recall and influenced competitive ability in the African striped mouse Rhabdomys dilectus chakae. Mice were subjected to five protein diet treatments, which they received continuously, or were raised on one diet to weaning and switched to an alternate diet post-weaning (Day 16): 1) HP-HP: high protein (24%); first letter pair indicates maternal diet and the second pair indicates offspring diet post-weaning; 2) BP-BP: baseline protein (19%); 3) LP-LP: low protein (10%); 4) HP-LP: switched from high to low protein diet; and 5) LP-HP: switched from low protein to high protein diet. From Day 70, when mice were sexually mature, 20 individuals (10 males, 10 females) per treatment were subjected to three successive experiments, in which we tested their anxiety responses in: 1) an open field arena (time spent in the centre of the open field); 2) novel object recognition (time spent exploring a novel object); and 3) social interactions (excluding BP-BP) in age-matched same-sex dyadic encounters (aggressive, amicable and avoidance behaviours). LP-LP and LP-HP treatment mice spent the least amount of time in the centre of the open field, did not demonstrate object preference compared to the other treatments, and were the most aggressive in dyadic encounters. Our study shows that the systemic effects of protein-deficient diets during early life shapes the behavioural phenotype in R. d. chakae, possibly through early organisation of neuro-biological pathways or competition among littermates. PMID:27080079

  6. Alteration in Memory and Electroencephalogram Waves with Sub-acute Noise Stress in Albino Rats and Safeguarded by Scoparia dulcis

    PubMed Central

    Loganathan, Sundareswaran; Rathinasamy, Sheeladevi

    2016-01-01

    Background: Noise stress has different effects on memory and novelty and the link between them with an electroencephalogram (EEG) has not yet been reported. Objective: To find the effect of sub-acute noise stress on the memory and novelty along with EEG and neurotransmitter changes. Materials and Methods: Eight-arm maze (EAM) and Y-maze to analyze the memory and novelty by novel object test. Four groups of rats were used: Control, control treated with Scoparia dulcis extract, noise exposed, and noise exposed which received Scoparia extract. Results: The results showed no marked difference observed between control and control treated with Scoparia extract on EAM, Y-maze, novel object test, and EEG in both prefrontal and occipital region, however, noise stress exposed rats showed significant increase in the reference memory and working memory error in EAM and latency delay, triad errors in Y-maze, and prefrontal and occipital EEG frequency rate with the corresponding increase in plasma corticosterone and epinephrine, and significant reduction in the novelty test, and significant reduction in the novelty test, amplitude of prefrontal, occipital EEG, and acetylcholine. Conclusion: These noise stress induced changes in EAM, Y-maze, novel object test, and neurotransmitters were significantly prevented when treated with Scoparia extract and these changes may be due to the normalizing action of Scoparia extract on the brain, which altered due to noise stress. SUMMARY Noise stress exposure causes EEG, behavior, and neurotransmitter alteration in the frontoparietal and occipital regions mainly involved in planning and recognition memoryOnly the noise stress exposed animals showed the significant alteration in the EEG, behavior, and neurotransmittersHowever, these noise stress induced changes in EEG behavior and neurotransmitters were significantly prevented when treated with Scoparia extractThese changes may be due to the normalizing action of Scoparia dulcis (adoptogen) on

  7. Can color changes alter the neural correlates of recognition memory? Manipulation of processing affects an electrophysiological indicator of conceptual implicit memory.

    PubMed

    Cui, Xiaoyu; Gao, Chuanji; Zhou, Jianshe; Guo, Chunyan

    2016-09-28

    It has been widely shown that recognition memory includes two distinct retrieval processes: familiarity and recollection. Many studies have shown that recognition memory can be facilitated when there is a perceptual match between the studied and the tested items. Most event-related potential studies have explored the perceptual match effect on familiarity on the basis of the hypothesis that the specific event-related potential component associated with familiarity is the FN400 (300-500 ms mid-frontal effect). However, it is currently unclear whether the FN400 indexes familiarity or conceptual implicit memory. In addition, on the basis of the findings of a previous study, the so-called perceptual manipulations in previous studies may also involve some conceptual alterations. Therefore, we sought to determine the influence of perceptual manipulation by color changes on recognition memory when the perceptual or the conceptual processes were emphasized. Specifically, different instructions (perceptually or conceptually oriented) were provided to the participants. The results showed that color changes may significantly affect overall recognition memory behaviorally and that congruent items were recognized with a higher accuracy rate than incongruent items in both tasks, but no corresponding neural changes were found. Despite the evident familiarity shown in the two tasks (the behavioral performance of recognition memory was much higher than at the chance level), the FN400 effect was found in conceptually oriented tasks, but not perceptually oriented tasks. It is thus highly interesting that the FN400 effect was not induced, although color manipulation of recognition memory was behaviorally shown, as seen in previous studies. Our findings of the FN400 effect for the conceptual but not perceptual condition support the explanation that the FN400 effect indexes conceptual implicit memory. PMID:27489100

  8. Lead-induced effects on learning/memory and fear/anxiety are correlated with disturbances in specific cholinesterase isoform activity and redox imbalance in adult brain.

    PubMed

    Ferlemi, Anastasia-Varvara; Avgoustatos, Dionisis; Kokkosis, Alexandros G; Protonotarios, Vasilis; Constantinou, Caterina; Margarity, Marigoula

    2014-05-28

    The aim of the present study was to investigate whether the underlying mechanism of lead (Pb)-induced effects on learning/memory and fear/anxiety behavior involves changes either on AChE G4 (most abundant in brain) or on G1 isoform activity, and/or to a putative local disruption of oxidant/antioxidant balance. Adult male mice were randomly divided into two groups (18 animals/group): a vehicle group [500ppm (mg/L) CH3COONa/day for 4weeks in their drinking water] and a Pb-treated group [500ppm Pb(CH3COO)2/day for 4weeks in their drinking water]. At the end of the treatment period, mice were subjected to the behavioral tasks. Learning/memory was tested by step-through passive avoidance test, whereas fear/anxiety was studied using the elevated plus-maze and thigmotaxis tests. Pb levels in mice brain were determined using atomic absorption spectrometry. AChE activity was determined colorimetrically, and GSH and MDA levels fluorometrically in whole brain minus cerebellum, cerebral cortex, midbrain, hippocampus, striatum and cerebellum. The possible correlations between learning/memory or fear/anxiety behavior with the AChE activity and/or the lipid peroxidation levels and GSH content were also examined. Pb consumption caused significant deficits on mice learning/memory ability and increased anxiety. The consumption of the Pb solution inhibited the activity of the two AChE isoforms in all brain regions tested. Moreover, Pb exposure increased lipid peroxidation and decreased GSH levels in all brain regions examined. Spearman correlation analysis revealed that the coefficients between the particular behaviors, AChE activity and redox balance were brain region- and AChE isoform-specific. PMID:24768645

  9. Divergent effects of isolation rearing on prepulse inhibition, activity, anxiety and hippocampal-dependent memory in Roman high- and low-avoidance rats: A putative model of schizophrenia-relevant features.

    PubMed

    Oliveras, Ignasi; Sánchez-González, Ana; Piludu, Maria Antonietta; Gerboles, Cristina; Río-Álamos, Cristóbal; Tobeña, Adolf; Fernández-Teruel, Alberto

    2016-11-01

    Social isolation of rats induces a constellation of behavioral alterations known as "isolation syndrome" that are consistent with some of the positive and cognitive symptoms observed in schizophrenic patients. In the present study we have assessed whether isolation rearing of inbred Roman high-avoidance (RHA-I) and Roman low-avoidance (RLA-I) strains can lead to the appearance of some of the key features of the "isolation syndrome", such as prepulse inhibition (PPI) deficits, increased anxious behavior, hyperactivity and memory/learning impairments. Compared to RLA-I rats, the results show that isolation rearing (IR) in RHA-I rats has a more profound impact, as they exhibit isolation-induced PPI deficits, increased anxiety, hyperactivity and long-term reference memory deficits, while isolated RLA-I rats only exhibit deficits in a spatial working memory task. These results give further support to the validity of RHA-I rats as a genetically-based model of schizophrenia relevant-symptoms. PMID:27478139

  10. Divergent effects of isolation rearing on prepulse inhibition, activity, anxiety and hippocampal-dependent memory in Roman high- and low-avoidance rats: A putative model of schizophrenia-relevant features.

    PubMed

    Oliveras, Ignasi; Sánchez-González, Ana; Piludu, Maria Antonietta; Gerboles, Cristina; Río-Álamos, Cristóbal; Tobeña, Adolf; Fernández-Teruel, Alberto

    2016-11-01

    Social isolation of rats induces a constellation of behavioral alterations known as "isolation syndrome" that are consistent with some of the positive and cognitive symptoms observed in schizophrenic patients. In the present study we have assessed whether isolation rearing of inbred Roman high-avoidance (RHA-I) and Roman low-avoidance (RLA-I) strains can lead to the appearance of some of the key features of the "isolation syndrome", such as prepulse inhibition (PPI) deficits, increased anxious behavior, hyperactivity and memory/learning impairments. Compared to RLA-I rats, the results show that isolation rearing (IR) in RHA-I rats has a more profound impact, as they exhibit isolation-induced PPI deficits, increased anxiety, hyperactivity and long-term reference memory deficits, while isolated RLA-I rats only exhibit deficits in a spatial working memory task. These results give further support to the validity of RHA-I rats as a genetically-based model of schizophrenia relevant-symptoms.

  11. Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors.

    PubMed

    Meyer, Danielle L; Davies, Daniel R; Barr, Jeffrey L; Manzerra, Pasquale; Forster, Gina L

    2012-06-01

    Recent reports suggest that experiencing a mild closed head trauma or mild traumatic brain injury (mTBI) is associated with a greater incidence of anxiety disorders. Dysfunction of limbic structures, such as the medial prefrontal cortex, amygdala and hippocampus, is associated with the symptoms of anxiety disorders. Therefore, the goal of the current studies was to characterize the consequences of closed mTBI on these limbic structures and associated fear and anxiety-related behaviors. A weight-drop procedure was employed to induce mTBI in male rats. Rats were transcardically perfused 4 or 9 days following exposure to mTBI or control procedures, and neuronal number, brain region area, and the number of apoptotic cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and acquisition, retention and extinction of contextual fear were also assessed. Findings suggest that mTBI was associated with significant neuronal cell loss in the CA1 region of the dorsal hippocampus and increased cell number in subregions of the amygdala, both of which appear to be related to alterations to apoptosis in these regions following mTBI. Furthermore, mTBI increased expression of anxiety-like behaviors and conditioned fear, with no effect on motor performance or nociception. Overall, a single impact to the skull to mimic mTBI in rats produces discrete alterations to neuronal numbers within the limbic system and specific emotional deficits, providing a potential neurobiological link between mTBI and anxiety disorders.

  12. Altered Distribution of Peripheral Blood Memory B Cells in Humans Chronically Infected with Trypanosoma cruzi

    PubMed Central

    Fernández, Esteban R.; Olivera, Gabriela C.; Quebrada Palacio, Luz P.; González, Mariela N.; Hernandez-Vasquez, Yolanda; Sirena, Natalia María; Morán, María L.; Ledesma Patiño, Oscar S.; Postan, Miriam

    2014-01-01

    Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans. PMID:25111833

  13. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    PubMed

    Fernández, Esteban R; Olivera, Gabriela C; Quebrada Palacio, Luz P; González, Mariela N; Hernandez-Vasquez, Yolanda; Sirena, Natalia María; Morán, María L; Ledesma Patiño, Oscar S; Postan, Miriam

    2014-01-01

    Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  14. Pharmacological elevation of anandamide impairs short-term memory by altering the neurophysiology in the hippocampus.

    PubMed

    Goonawardena, Anushka V; Sesay, John; Sexton, Cheryl Ann; Riedel, Gernot; Hampson, Robert E

    2011-01-01

    In rodents, many exogenous cannabinoid agonists including Δ(9)-THC and WIN55,212-2 (WIN-2) have been shown to impair short-term memory (STM) by inhibition of hippocampal neuronal assemblies. However, the mechanisms by which endocannabinoids such as anandamide and 2-arachidonyl glycerol (2-AG) modulate STM processes are not well understood. Here the effects of anandamide on performance of a Delayed-Non-Match-to-Sample (DNMS) task (i.e. STM task) and concomitant hippocampal ensemble activity were assessed following administration of either URB597 (0.3, 3.0 mg/kg), an inhibitor of the Fatty Acid Amide Hydrolase (FAAH), AM404 (1.5, 10.0 mg/kg), a putative anandamide uptake/FAAH inhibitor, or R-methanandamide (3.0, 10.0 mg/kg), a stable analog of anandamide. Principal cells from hippocampal CA3/CA1 were recorded extracellularly by multi-electrode arrays in Long-Evans rats during DNMS task (1-30 s delays) performance and tracked throughout drug administration and recovery. Both R-methanandamide and URB597 caused dose- and delay-dependent deficits in DNMS performance with suppression of hippocampal ensemble activity during the encoding (sample) phase. R-methanandamide-induced effects were not reversed by capsaicin excluding a contribution of TRPV-1 receptors. AM404 produced subtle deficits at longer delay intervals but did not alter hippocampal neuronal activity during task-specific events. Collectively, these data indicate that endocannabinoid levels affect performance in a STM task and their pharmacological elevation beyond normal concentrations is detrimental also for the underlying physiological responses. They also highlight a specific window of memory processing, i.e. encoding, which is sensitive to cannabinoid modulation.

  15. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    PubMed

    Fernández, Esteban R; Olivera, Gabriela C; Quebrada Palacio, Luz P; González, Mariela N; Hernandez-Vasquez, Yolanda; Sirena, Natalia María; Morán, María L; Ledesma Patiño, Oscar S; Postan, Miriam

    2014-01-01

    Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans. PMID:25111833

  16. Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats.

    PubMed

    de Senna, Priscylla Nunes; Ilha, Jocemar; Baptista, Pedro Porto Alegre; do Nascimento, Patrícia Severo; Leite, Marina Concli; Paim, Mariana Fontoura; Gonçalves, Carlos Alberto; Achaval, Matilde; Xavier, Léder Leal

    2011-12-01

    Type 1 diabetes mellitus (T1DM) is associated with neurocognitive dysfunction and astrogliosis. Physical exercise prevents cognitive impairments and induces important brain modifications. The aim of our study was to investigate the effect of treadmill exercise on spatial memory and astrocytic function in the hippocampus of a T1DM model. Fifty-seven Wistar rats were divided into four groups: trained control (TC) (n = 15), non-trained control (NTC) (n = 13), trained diabetic (TD) (n = 14) and non-trained diabetic (NTD) (n = 15). One month after streptozotocin-induced diabetes, exercise groups were submitted to 5 weeks of physical training, and then, all groups were assessed in the novel object-placement recognition task. Locomotor activity was analyzed in the open field apparatus using Any-maze software. The expression of glial fibrillary acidic protein (GFAP) and S100B in hippocampus and cerebrospinal fluid were measured using ELISA assay, and hippocampal GFAP immunoreactivity was evaluated by means of immunohistochemistry and optical densitometry. The results showed that physical exercise prevents and/or reverts spatial memory impairments observed in NTD animals (P < 0.01). Decreased locomotor activity was observed in both the NTD and TD groups when compared with controls (P < 0.05). ELISA and immunohistochemistry analyzes showed there was a reduction in GFAP levels in the hippocampus of NTD animals, which was not found in TD group. ELISA also showed an increase in S100B levels in the cerebrospinal fluid from the NTD group (P < 0.01) and no such increase was found in the TD group. Our findings indicate that physical exercise prevents and/or reverts the cognitive deficits and astroglial alterations induced by T1DM.

  17. The elevated T-maze task as an animal model to simultaneously investigate the effects of drugs on long-term memory and anxiety in mice.

    PubMed

    Asth, Laila; Lobão-Soares, Bruno; André, Eunice; Soares, Vanessa de Paula; Gavioli, Elaine Cristina

    2012-04-10

    The elevated T-maze (ETM) is an apparatus derived from the elevated plus-maze test, which is used to evaluate anxiety. Because anxiety is a biasing factor in models of memory, this study proposed the ETM as a task for the simultaneous assessment of memory and anxiety in mice. The ETM consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. The anxiolytic diazepam (DZP; 1 or 2mg/kg) and the amnestic biperiden (BPR; 0.5, 1 or 3mg/kg) were injected at three distinct times: pre-training, post-training, and pre-test. Pre-training administration of BPR 1 and DZP 2 increased the number of trials needed to reach the avoidance criterion, suggesting a passive avoidance learning impairment. However, BPR induced hyperlocomotion, which could bias the interpretation of any BPR-induced effects during the training session. Pre-training injection of BPR did not affect the spontaneous increase in the latency to enter an open arm between trials, while DZP reduced latencies in the first three trials suggesting anxiolysis. In the test session, pre-training injection of BPR 1 and DZP 2 reduced latencies to enter an open arm, indicating memory impairment. Post-training and pre-test injection of DZP or BPR did not affect memory. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs.

  18. Test Anxiety among College Students with Specific Reading Disability (Dyslexia): Nonverbal Ability and Working Memory as Predictors

    ERIC Educational Resources Information Center

    Nelson, Jason M.; Lindstrom, Will; Foels, Patricia A.

    2015-01-01

    Test anxiety and its correlates were examined with college students with and without specific reading disability (RD; n = 50 in each group). Results indicated that college students with RD reported higher test anxiety than did those without RD, and the magnitude of these differences was in the medium range on two test anxiety scales. Relative to…

  19. Memory

    MedlinePlus

    ... it has to decide what is worth remembering. Memory is the process of storing and then remembering this information. There are different types of memory. Short-term memory stores information for a few ...

  20. HIV- and FIV-derived gp120 alter spatial memory, LTP, and sleep in rats.

    PubMed

    Sánchez-Alavez, M; Criado, J; Gómez-Chavarín, M; Jiménez-Anguiano, A; Navarro, L; Díaz-Ruiz, O; Galicia, O; Sánchez-Narváez, F; Murillo-Rodríguez, E; Henriksen, S J; Elder, J H; Prospéro-García, O

    2000-08-01

    Human immunodeficiency virus (HIV)-associated dementia (HAD) has been detected in 20-30% of patients suffering AIDS. The envelope glycoprotein 120 (gp120) derived from HIV seems to play a critical role in the pathophysiology of this dementia. Likewise, the feline immunodeficiency virus (FIV)-derived gp120 causes neurological and electrophysiological abnormalitites in cats. We have studied the effects of gp120 derived from HIV or FIV on learning and memory processing, hippocampal long-term potentiation (LTP), hippocampal neuronal cAMP production, the sleep-waking cycle, and locomotor activity and equilibrium in rats. Results showed that while both HIV- and FIV-gp120 impaired the rat's performance in the Barnes maze task, only HIVgp120 impaired the induction and maintenance of LTP. However, both glycoproteins induced a significant decrease in the posttetanic potentiation. HIVgp120 also caused a significant reduction in cAMP production in the hippocampus. Regarding the sleep-waking cycle, HIV- and FIV-gp120 increased the waking state and slow-wave sleep 1 (SWS1), while decreasing both SWS2 and REM sleep. Locomotor activity and equilibrium were significantly altered by these glycoproteins. These results suggest that HIVgp120 causes neurophysiological abnormalities and therefore may facilitate HAD development in AIDS patients.

  1. Age-related alterations in default mode network: impact on working memory performance.

    PubMed

    Sambataro, Fabio; Murty, Vishnu P; Callicott, Joseph H; Tan, Hao-Yang; Das, Saumitra; Weinberger, Daniel R; Mattay, Venkata S

    2010-05-01

    The default mode network (DMN) is a set of functionally connected brain regions which shows deactivation (task-induced deactivation, TID) during a cognitive task. Evidence shows an age-related decline in task-load-related modulation of the activity within the DMN during cognitive tasks. However, the effect of age on the functional coupling within the DMN and their relation to cognitive performance has hitherto been unexplored. Using functional magnetic resonance imaging, we investigated functional connectivity within the DMN in older and younger subjects during a working memory task with increasing task load. Older adults showed decreased connectivity and ability to suppress low frequency oscillations of the DMN. Additionally, the strength of the functional coupling of posterior cingulate (pCC) with medial prefrontal cortex (PFC) correlated positively with performance and was lower in older adults. pCC was also negatively coupled with task-related regions, namely the dorsolateral PFC and cingulate regions. Our results show that in addition to changes in canonical task-related brain regions, normal aging is also associated with alterations in the activity and connectivity of brain regions within the DMN. These changes may be a reflection of a deficit in cognitive control associated with advancing age that results in deficient resource allocation to the task at hand.

  2. Altered Gene Regulation and Synaptic Morphology in "Drosophila" Learning and Memory Mutants

    ERIC Educational Resources Information Center

    Guan, Zhuo; Buhl, Lauren K.; Quinn, William G.; Littleton, J. Troy

    2011-01-01

    Genetic studies in "Drosophila" have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in "radish" ("rsh") mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways…

  3. AIM 2 inflammasomes regulate neuronal morphology and influence anxiety and memory in mice

    PubMed Central

    Wu, Pei-Jung; Liu, Hsin-Yu; Huang, Tzyy-Nan; Hsueh, Yi-Ping

    2016-01-01

    Inflammasomes are the protein assemblies that consist of inflammasome sensors, adaptor apoptosis-associated speck-like proteins containing a CARD (ASC) and inflammasome caspase. Inflammasomes sense multiple danger signals via various inflammasome sensors and consequently use caspase to trigger proteolytic processing and secretion of IL-1β cytokines. Recent studies have suggested that neurons use their own innate immune system to detect danger signals and regulate neuronal morphology. Here, we investigate whether inflammasomes, the critical components of innate immunity, participate in regulation of neuronal morphology and function. Among various sensors, Absent in melanoma 2 (Aim2) expression in neurons is most prominent. Adding synthetic double-stranded DNA (dsDNA) to cultured neurons induces IL-1β secretion in an AIM2-dependent manner and consequently downregulates dendritic growth but enhances axon extension. The results of Aim2 knockout and knockdown show that AIM2 acts cell-autonomously to regulate neuronal morphology. Behavioral analyses further reveal that Aim2−/− mice exhibit lower locomotor activity, increased anxious behaviors and reduced auditory fear memory. In conclusion, our study suggests that AIM2 inflammasomes regulate neuronal morphology and influence mouse behaviors. PMID:27561456

  4. AIM 2 inflammasomes regulate neuronal morphology and influence anxiety and memory in mice.

    PubMed

    Wu, Pei-Jung; Liu, Hsin-Yu; Huang, Tzyy-Nan; Hsueh, Yi-Ping

    2016-01-01

    Inflammasomes are the protein assemblies that consist of inflammasome sensors, adaptor apoptosis-associated speck-like proteins containing a CARD (ASC) and inflammasome caspase. Inflammasomes sense multiple danger signals via various inflammasome sensors and consequently use caspase to trigger proteolytic processing and secretion of IL-1β cytokines. Recent studies have suggested that neurons use their own innate immune system to detect danger signals and regulate neuronal morphology. Here, we investigate whether inflammasomes, the critical components of innate immunity, participate in regulation of neuronal morphology and function. Among various sensors, Absent in melanoma 2 (Aim2) expression in neurons is most prominent. Adding synthetic double-stranded DNA (dsDNA) to cultured neurons induces IL-1β secretion in an AIM2-dependent manner and consequently downregulates dendritic growth but enhances axon extension. The results of Aim2 knockout and knockdown show that AIM2 acts cell-autonomously to regulate neuronal morphology. Behavioral analyses further reveal that Aim2-/- mice exhibit lower locomotor activity, increased anxious behaviors and reduced auditory fear memory. In conclusion, our study suggests that AIM2 inflammasomes regulate neuronal morphology and influence mouse behaviors. PMID:27561456

  5. Sex and Exercise Interact to Alter the Expression of Anabolic Androgenic Steroid-Induced Anxiety-Like Behaviors in the Mouse

    PubMed Central

    Onakomaiya, Marie M.; Porter, Donna M.; Oberlander, Joseph G.; Henderson, Leslie P.

    2014-01-01

    Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711

  6. Sex and exercise interact to alter the expression of anabolic androgenic steroid-induced anxiety-like behaviors in the mouse.

    PubMed

    Onakomaiya, Marie M; Porter, Donna M; Oberlander, Joseph G; Henderson, Leslie P

    2014-07-01

    Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711

  7. Sex and exercise interact to alter the expression of anabolic androgenic steroid-induced anxiety-like behaviors in the mouse.

    PubMed

    Onakomaiya, Marie M; Porter, Donna M; Oberlander, Joseph G; Henderson, Leslie P

    2014-07-01

    Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala.

  8. Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice.

    PubMed

    Li, Xia; Risbrough, Victoria B; Cates-Gatto, Chelsea; Kaczanowska, Katarzyna; Finn, M G; Roberts, Amanda J; Markou, Athina

    2013-07-01

    γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory. In addition, the effects of BHF177 were compared with the agonist baclofen. Unlike the anxiolytic chlordiazepoxide, baclofen (0.5, 1.5, and 2.5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or Vogel conflict test. Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen. At the highest dose tested (2.5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i.e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects. BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific. At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze. These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice.

  9. Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats

    PubMed Central

    Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

    2015-01-01

    Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes. PMID:26716991

  10. Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

    PubMed

    Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

    2015-01-01

    Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes. PMID:26716991

  11. Altered neural network supporting declarative long-term memory in mild cognitive impairment.

    PubMed

    Poettrich, Katrin; Weiss, Peter H; Werner, Annett; Lux, Silke; Donix, Markus; Gerber, Johannes; von Kummer, Rüdiger; Fink, Gereon R; Holthoff, Vjera A

    2009-02-01

    Autobiographical episodic memory represents a subsystem of declarative long-term memory and largely depends on combining information from multiple sources. The purpose of this study was to assess neural correlates of declarative long-term memory in patients with amnestic mild cognitive impairment (MCI) and controls using fMRI and a task requiring autobiographical and semantic memory retrieval. Comparison of the network supporting episodic autobiographical and semantic memory irrespective of remoteness (recent and remote) revealed significant activations in right parietal cortex and precuneus bilaterally in the patients. Autobiographical episodic versus semantic memory retrieval in the controls led to significant bilateral activations of the parietal-temporal junction, left temporal pole, anterior cingulate, retrosplenial cortex and cerebellum. In contrast, MCI patients activated left supplementary motor area, left premotor and superior temporal cortex. In MCI patients compared to controls a dysfunction of the retrosplenial cortex during memory retrieval was revealed by a lack of differential activation in relation to recency of memories and memory type. Our data suggest that MCI leads to a loss of specificity in the neural network supporting declarative long-term memory.

  12. Altered source memory retrieval is associated with pathological doubt in obsessive-compulsive disorder.

    PubMed

    Olson, Christy A; Hale, Lisa R; Hamilton, Nancy; Powell, Joshua N; Martin, Laura E; Savage, Cary R

    2016-01-01

    Individuals with obsessive-compulsive disorder (OCD) often complain of doubt related to memory. As neuropsychological research has demonstrated that individuals with OCD tend to focus on details and miss the larger context, the construct of source (contextual) memory may be particularly relevant to memory complaints in OCD. Memory for object versus contextual information relies on partially distinct regions within the prefrontal cortex, parietal and medial temporal lobe, and may be differentially impacted by OCD. In the present study, we sought to test the hypothesis that individuals with OCD exhibit impaired source memory retrieval using a novel memory paradigm - The Memory for Rooms Test (MFRT) - a four-room memory task in which participants walk through four rooms and attempt to encode and remember objects. Demographically matched individuals with OCD and healthy controls studied objects in the context of four rooms, and then completed a memory retrieval test while undergoing functional magnetic resonance imaging (fMRI). While no differences were observed in source memory accuracy, individuals with OCD exhibited greater task related activation in the posterior cingulate cortex (PCC) relative to healthy controls during correct source memory retrieval. During correct object recognition, individuals with OCD failed to recruit the dorsolateral prefrontal(DLPFC)/premotor, left mPFC, and right parietal regions to the same extent as healthy controls. Our results suggest abnormal recruitment of frontal-parietal and PCC regions during source verses object memory retrieval in OCD. Within the OCD group, activation in the PCC and the premotor/DLPFC was associated with greater pathological doubt. This finding is consistent with the observation that OCD patients often experience extreme doubt, even when memory performance is intact. PMID:26315458

  13. Memory.

    ERIC Educational Resources Information Center

    McKean, Kevin

    1983-01-01

    Discusses current research (including that involving amnesiacs and snails) into the nature of the memory process, differentiating between and providing examples of "fact" memory and "skill" memory. Suggests that three brain parts (thalamus, fornix, mammilary body) are involved in the memory process. (JN)

  14. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder.

    PubMed

    Patki, Gaurav; Li, Lumeng; Allam, Farida; Solanki, Naimesh; Dao, An T; Alkadhi, Karim; Salim, Samina

    2014-05-10

    Post-traumatic stress disorder (PTSD) is a condition which can develop from exposure to a severe traumatic event such as those occurring during wars or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are considered the gold standard for PTSD treatment, but their side effects pose a serious problem. While regular physical exercise is regarded as a mood elevator and known to enhance cognitive function, its direct role in rescuing core symptoms of PTSD including anxiety and depression-like behaviors and cognitive impairment is unclear. In the present study using the single-prolonged stress (SPS) rat model of PTSD (2h restrain, 20 min forced swimming, 15 min rest, and 1-2 min diethyl ether exposure), we examined the beneficial effect of moderate treadmill exercise on SPS-induced behavioral deficits including anxiety and depression-like behaviors and memory impairment. Male Wistar rats were randomly assigned into four groups: control (sedentary), exercised, SPS (no exercise), or SPS-exercised. Rats were exercised on a rodent treadmill for 14 consecutive days. Rats in all groups were tested for anxiety-like behaviors using open field (OF), light-dark and elevated-plus maze tests. All rats were tested for short-term and long-term memory in the radial arm water maze test. Rats were then sacrificed, blood was collected (for corticosterone levels), and individual organs (spleen, adrenals, and thymus) harvested. Results suggest that moderate physical exercise ameliorates SPS-induced behavioral deficits in rats.

  15. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder

    PubMed Central

    Patki, Gaurav; Li, Lumeng; Allam, Farida; Solanki, Naimesh; Dao, An T; Alkadhi, Karim; Salim, Samina

    2015-01-01

    Post-traumatic stress disorder (PTSD) is a condition which can develop from exposure to a severe traumatic event such as those occurring during wars or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are considered the gold standard for PTSD treatment, but their side effects pose a serious problem. While regular physical exercise is regarded as a mood elevator and known to enhance cognitive function, its direct role in rescuing core symptoms of PTSD including anxiety and depression-like behaviors and cognitive impairment is unclear. In the present study using the single-prolonged stress (SPS) rat model of PTSD (2h restrain, 20 min forced swimming, 15 min rest, and 1–2 min diethyl ether exposure), we examined the beneficial effect of moderate treadmill exercise on SPS-induced behavioral deficits including anxiety and depression-like behaviors and memory impairment. Male Wistar rats were randomly assigned into four groups: control (sedentary), exercised, SPS (no exercise), or SPS-exercised. Rats were exercised on a rodent treadmill for 14 consecutive days. Rats in all groups were tested for anxiety-like behaviors using open field (OF), light-dark and elevated-plus maze tests. All rats were tested for short-term and long-term memory in the radial arm water maze test. Rats were then sacrificed, blood was collected (for corticosterone levels), and individual organs (spleen, adrenals, and thymus) harvested. Results suggest that moderate physical exercise ameliorates SPS-induced behavioral deficits in rats. PMID:24657739

  16. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder.

    PubMed

    Patki, Gaurav; Li, Lumeng; Allam, Farida; Solanki, Naimesh; Dao, An T; Alkadhi, Karim; Salim, Samina

    2014-05-10

    Post-traumatic stress disorder (PTSD) is a condition which can develop from exposure to a severe traumatic event such as those occurring during wars or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are considered the gold standard for PTSD treatment, but their side effects pose a serious problem. While regular physical exercise is regarded as a mood elevator and known to enhance cognitive function, its direct role in rescuing core symptoms of PTSD including anxiety and depression-like behaviors and cognitive impairment is unclear. In the present study using the single-prolonged stress (SPS) rat model of PTSD (2h restrain, 20 min forced swimming, 15 min rest, and 1-2 min diethyl ether exposure), we examined the beneficial effect of moderate treadmill exercise on SPS-induced behavioral deficits including anxiety and depression-like behaviors and memory impairment. Male Wistar rats were randomly assigned into four groups: control (sedentary), exercised, SPS (no exercise), or SPS-exercised. Rats were exercised on a rodent treadmill for 14 consecutive days. Rats in all groups were tested for anxiety-like behaviors using open field (OF), light-dark and elevated-plus maze tests. All rats were tested for short-term and long-term memory in the radial arm water maze test. Rats were then sacrificed, blood was collected (for corticosterone levels), and individual organs (spleen, adrenals, and thymus) harvested. Results suggest that moderate physical exercise ameliorates SPS-induced behavioral deficits in rats. PMID:24657739

  17. Altered functional connectivity in the brain default-mode network of earthquake survivors persists after 2 years despite recovery from anxiety symptoms.

    PubMed

    Du, Ming-Ying; Liao, Wei; Lui, Su; Huang, Xiao-Qi; Li, Fei; Kuang, Wei-Hong; Li, Jing; Chen, Hua-Fu; Kendrick, Keith Maurice; Gong, Qi-Yong

    2015-11-01

    Although acute impact of traumatic experiences on brain function in disaster survivors is similar to that observed in post-traumatic stress disorders (PTSD), little is known about the long-term impact of this experience. We have used structural and functional magnetic resonance imaging to investigate resting-state functional connectivity and gray and white matter (WM) changes occurring in the brains of healthy Wenchuan earthquake survivors both 3 weeks and 2 years after the disaster. Results show that while functional connectivity changes 3 weeks after the disaster involved both frontal-limbic-striatal and default-mode networks (DMN), at the 2-year follow-up only changes in the latter persisted, despite complete recovery from high initial levels of anxiety. No gray or WM volume changes were found at either time point. Taken together, our findings provide important new evidence that while altered functional connectivity in the frontal-limbic-striatal network may underlie the post-trauma anxiety experienced by survivors, parallel changes in the DMN persist despite the apparent absence of anxiety symptoms. This suggests that long-term changes occur in neural networks involved in core aspects of self-processing, cognitive and emotional functioning in disaster survivors which are independent of anxiety symptoms and which may also confer increased risk of subsequent development of PTSD. PMID:25862672

  18. Altered functional connectivity in the brain default-mode network of earthquake survivors persists after 2 years despite recovery from anxiety symptoms

    PubMed Central

    Du, Ming-Ying; Liao, Wei; Huang, Xiao-Qi; Li, Fei; Kuang, Wei-Hong; Li, Jing; Chen, Hua-Fu; Kendrick, Keith Maurice; Gong, Qi-Yong

    2015-01-01

    Although acute impact of traumatic experiences on brain function in disaster survivors is similar to that observed in post-traumatic stress disorders (PTSD), little is known about the long-term impact of this experience. We have used structural and functional magnetic resonance imaging to investigate resting-state functional connectivity and gray and white matter (WM) changes occurring in the brains of healthy Wenchuan earthquake survivors both 3 weeks and 2 years after the disaster. Results show that while functional connectivity changes 3 weeks after the disaster involved both frontal–limbic–striatal and default-mode networks (DMN), at the 2-year follow-up only changes in the latter persisted, despite complete recovery from high initial levels of anxiety. No gray or WM volume changes were found at either time point. Taken together, our findings provide important new evidence that while altered functional connectivity in the frontal–limbic–striatal network may underlie the post-trauma anxiety experienced by survivors, parallel changes in the DMN persist despite the apparent absence of anxiety symptoms. This suggests that long-term changes occur in neural networks involved in core aspects of self-processing, cognitive and emotional functioning in disaster survivors which are independent of anxiety symptoms and which may also confer increased risk of subsequent development of PTSD. PMID:25862672

  19. Membrane Capacitive Memory Alters Spiking in Neurons Described by the Fractional-Order Hodgkin-Huxley Model

    PubMed Central

    Weinberg, Seth H.

    2015-01-01

    Excitable cells and cell membranes are often modeled by the simple yet elegant parallel resistor-capacitor circuit. However, studies have shown that the passive properties of membranes may be more appropriately modeled with a non-ideal capacitor, in which the current-voltage relationship is given by a fractional-order derivative. Fractional-order membrane potential dynamics introduce capacitive memory effects, i.e., dynamics are influenced by a weighted sum of the membrane potential prior history. However, it is not clear to what extent fractional-order dynamics may alter the properties of active excitable cells. In this study, we investigate the spiking properties of the neuronal membrane patch, nerve axon, and neural networks described by the fractional-order Hodgkin-Huxley neuron model. We find that in the membrane patch model, as fractional-order decreases, i.e., a greater influence of membrane potential memory, peak sodium and potassium currents are altered, and spike frequency and amplitude are generally reduced. In the nerve axon, the velocity of spike propagation increases as fractional-order decreases, while in a neural network, electrical activity is more likely to cease for smaller fractional-order. Importantly, we demonstrate that the modulation of the peak ionic currents that occurs for reduced fractional-order alone fails to reproduce many of the key alterations in spiking properties, suggesting that membrane capacitive memory and fractional-order membrane potential dynamics are important and necessary to reproduce neuronal electrical activity. PMID:25970534

  20. Cysteamine treatment ameliorates alterations in GAD67 expression and spatial memory in heterozygous reeler mice.

    PubMed

    Kutiyanawalla, Ammar; Promsote, Wanwisa; Terry, Alvin; Pillai, Anilkumar

    2012-09-01

    Brain-derived neurotrophic factor (BDNF) signalling through its receptor, TrkB is known to regulate GABAergic function and glutamic acid decarboxylase (GAD) 67 expression in neurons. Alterations in BDNF signalling have been implicated in the pathophysiology of schizophrenia and as a result, they are a potential therapeutic target. Interestingly, heterozygous reeler mice (HRM) have decreased GAD67 expression in the frontal cortex and hippocampus and they exhibit many behavioural and neurochemical abnormalities similar to schizophrenia. In this study, we evaluated the potential of cysteamine, a neuroprotective compound to improve the deficits in GAD67 expression and cognitive function in HRM. We found that cysteamine administration (150 mg/kg.d, through drinking water) for 30 d significantly ameliorated the decreases in GAD67, mature BDNF and full-length TrkB protein levels found in frontal cortex and hippocampus of HRM. A significant attenuation of the increased levels of truncated BDNF in frontal cortex and hippocampus, as well as truncated TrkB in frontal cortex of HRM was also observed following cysteamine treatment. In behavioural studies, HRM were impaired in a Y-maze spatial recognition memory task, but not in a spontaneous alternation task or a sensorimotor, prepulse inhibition (PPI) procedure. Cysteamine improved Y-maze spatial recognition in HRM to the level of wide-type controls and it improved PPI in both wild-type and HRM. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in GAD67 expression suggesting that TrkB signalling plays an important role in GAD67 regulation by cysteamine.

  1. The Memory Alteration Test Discriminates between Cognitively Healthy Status, Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Nuñez del Prado, Liza; Parodi, José; Guevara-Silva, Erik; Castro-Suarez, Sheila; Montesinos, Rosa; Cortijo, Patricia

    2014-01-01

    Background/Aims Dementia is a worldwide public health problem and there are several diagnostic tools for its assessment. The aim of this study was to evaluate the performance of the Memory Alteration Test (M@T) to discriminate between patients with early Alzheimer's disease (AD), patients with amnestic mild cognitive impairment (a-MCI), and subjects with a cognitively healthy status (CHS). Methods The discriminative validity was assessed in a sample of 90 patients with AD, 45 patients with a-MCI, and 180 subjects with CHS. Clinical, functional, and cognitive studies were independently performed in a blinded fashion and the gold standard diagnosis was established by consensus on the basis of these results. The test performance was assessed by means of a receiver operating characteristic curve analysis as area under the curve (AUC). Results M@T mean scores were 17.7 (SD = 5.7) in AD, 30.8 (SD = 2.3) in a-MCI, and 44.5 (SD = 3.1) in CHS. A cutoff score of 37 points had a sensitivity of 98.3% and a specificity of 97.8% to differentiate a-MCI from CHS (AUC = 0.999). A cutoff score of 27 points had a sensitivity of 100% and a specificity of 98.9% to differentiate mild AD from a-MCI and from CHS (AUC = 1.000). Conclusions The M@T had a high performance in the discrimination between early AD, a-MCI and CHS. PMID:25298775

  2. cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

    PubMed

    Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B

    2014-10-01

    Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response. PMID:24752151

  3. d-amino acid oxidase knockout (Dao(-/-) ) mice show enhanced short-term memory performance and heightened anxiety, but no sleep or circadian rhythm disruption.

    PubMed

    Pritchett, David; Hasan, Sibah; Tam, Shu K E; Engle, Sandra J; Brandon, Nicholas J; Sharp, Trevor; Foster, Russell G; Harrison, Paul J; Bannerman, David M; Peirson, Stuart N

    2015-05-01

    d-amino acid oxidase (DAO, DAAO) is an enzyme that degrades d-serine, the primary endogenous co-agonist of the synaptic N-methyl-d-aspartate receptor. Convergent evidence implicates DAO in the pathophysiology and potential treatment of schizophrenia. To better understand the functional role of DAO, we characterized the behaviour of the first genetically engineered Dao knockout (Dao(-/-) ) mouse. Our primary objective was to assess both spatial and non-spatial short-term memory performance. Relative to wildtype (Dao(+/+) ) littermate controls, Dao(-/-) mice demonstrated enhanced spatial recognition memory performance, improved odour recognition memory performance, and enhanced spontaneous alternation in the T-maze. In addition, Dao(-/-) mice displayed increased anxiety-like behaviour in five tests of approach/avoidance conflict: the open field test, elevated plus maze, successive alleys, light/dark box and novelty-suppressed feeding. Despite evidence of a reciprocal relationship between anxiety and sleep and circadian function in rodents, we found no evidence of sleep or circadian rhythm disruption in Dao(-/-) mice. Overall, our observations are consistent with, and extend, findings in the natural mutant ddY/Dao(-) line. These data add to a growing body of preclinical evidence linking the inhibition, inactivation or deletion of DAO with enhanced cognitive performance. Our results have implications for the development of DAO inhibitors as therapeutic agents.

  4. H₁ but not H₂ histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing.

    PubMed

    Serafim, K R; Kishi, M S; Canto-de-Souza, A; Mattioli, R

    2013-05-01

    This study investigated the role of H₁ and H₂ receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H₁ receptor, but not H₂, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

  5. H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

    PubMed Central

    Serafim, K.R.; Kishi, M.S.; Canto-de-Souza, A.; Mattioli, R.

    2013-01-01

    This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing. PMID:23598647

  6. Exercise affects memory acquisition, anxiety-like symptoms and activity of membrane-bound enzyme in brain of rats fed with different dietary fats: impairments of trans fat.

    PubMed

    Teixeira, A M; Pase, C S; Boufleur, N; Roversi, K; Barcelos, R C S; Benvegnú, D M; Segat, H J; Dias, V T; Reckziegel, P; Trevizol, F; Dolci, G S; Carvalho, N R; Soares, F A A; Rocha, J B T; Emanuelli, T; Bürger, M E

    2011-11-10

    Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.

  7. Item Strength Influences Source Confidence and Alters Source Memory zROC Slopes

    ERIC Educational Resources Information Center

    Starns, Jeffrey J.; Ksander, John C.

    2016-01-01

    Increasing the number of study trials creates a crossover pattern in source memory zROC slopes; that is, the slope is either below or above 1 depending on which source receives stronger learning. This pattern can be produced if additional learning affects memory processes such as the relative contribution of recollection and familiarity to source…

  8. Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria.

    PubMed

    Li, Wang; Dowd, Scot E; Scurlock, Bobbie; Acosta-Martinez, Veronica; Lyte, Mark

    2009-03-23

    The ability of dietary manipulation to influence learning and behavior is well recognized and almost exclusively interpreted as direct effects of dietary constituents on the central nervous system. The role of dietary modification on gut bacterial populations and the possibility of such microbial population shifts related to learning and behavior is poorly understood. The purpose of this study was to examine whether shifts in bacterial diversity due to dietary manipulation could be correlated with changes in memory and learning. Five week old male CF1 mice were randomly assigned to receive standard rodent chow (PP diet) or chow containing 50% lean ground beef (BD diet) for 3 months. As a measure of memory and learning, both groups were trained and tested on a hole-board open field apparatus. Following behavioral testing, all mice were sacrificed and colonic stool samples collected and analyzed by automated rRNA intergenic spacer analysis (ARISA) and bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) approach for microbial diversity. Results demonstrated significantly higher bacterial diversity in the beef supplemented diet group according to ARISA and bTEFAP. Compared to the PP diet, the BD diet fed mice displayed improved working (P=0.0008) and reference memory (P<0.0001). The BD diet fed animals also displayed slower speed (P<0.0001) in seeking food as well as reduced anxiety level in the first day of testing (P=0.0004). In conclusion, we observed a correlation between dietary induced shifts in bacteria diversity and animal behavior that may indicate a role for gut bacterial diversity in memory and learning. PMID:19135464

  9. Altered Neural Activity during Semantic Object Memory Retrieval in Amnestic Mild Cognitive Impairment as Measured by Event-Related Potentials.

    PubMed

    Chiang, Hsueh-Sheng; Mudar, Raksha A; Pudhiyidath, Athula; Spence, Jeffrey S; Womack, Kyle B; Cullum, C Munro; Tanner, Jeremy A; Eroh, Justin; Kraut, Michael A; Hart, John

    2015-01-01

    Deficits in semantic memory in individuals with amnestic mild cognitive impairment (aMCI) have been previously reported, but the underlying neurobiological mechanisms remain to be clarified. We examined event-related potentials (ERPs) associated with semantic memory retrieval in 16 individuals with aMCI as compared to 17 normal controls using the Semantic Object Retrieval Task (EEG SORT). In this task, subjects judged whether pairs of words (object features) elicited retrieval of an object (retrieval trials) or not (non-retrieval trials). Behavioral findings revealed that aMCI subjects had lower accuracy scores and marginally longer reaction time compared to controls. We used a multivariate analytical technique (STAT-PCA) to investigate similarities and differences in ERPs between aMCI and control groups. STAT-PCA revealed a left fronto-temporal component starting at around 750 ms post-stimulus in both groups. However, unlike controls, aMCI subjects showed an increase in the frontal-parietal scalp potential that distinguished retrieval from non-retrieval trials between 950 and 1050 ms post-stimulus negatively correlated with the performance on the logical memory subtest of the Wechsler Memory Scale-III. Thus, individuals with aMCI were not only impaired in their behavioral performance on SORT relative to controls, but also displayed alteration in the corresponding ERPs. The altered neural activity in aMCI compared to controls suggests a more sustained and effortful search during object memory retrieval, which may be a potential marker indicating disease processes at the pre-dementia stage.

  10. 17ß-Estradiol Regulates Histone Alterations Associated with Memory Consolidation and Increases "Bdnf" Promoter Acetylation in Middle-Aged Female Mice

    ERIC Educational Resources Information Center

    Fortress, Ashley M.; Kim, Jaekyoon; Poole, Rachel L.; Gould, Thomas J.; Frick, Karyn M.

    2014-01-01

    Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age-related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17ß-estradiol…

  11. Brooding Is Related to Neural Alterations during Autobiographical Memory Retrieval in Aging

    PubMed Central

    Schneider, Sophia; Brassen, Stefanie

    2016-01-01

    Brooding rumination is considered a central aspect of depression in midlife. As older people tend to review their past, rumination tendency might be particularly crucial in late life since it might hinder older adults to adequately evaluate previous events. We scanned 22 non-depressed older adults with varying degrees of brooding tendency with functional magnetic resonance imaging (MRI) while they performed the construction and elaboration of autobiographical memories. Behavioral findings demonstrate that brooders reported lower mood states, needed more time for memory construction and rated their memories as less detailed and less positive. On the neural level, brooding tendency was related to increased amygdala activation during the search for specific memories and reduced engagement of cortical networks during elaboration. Moreover, coupling patterns of the subgenual cingulate cortex with the hippocampus (HC) and the amygdala predicted details and less positive valence of memories in brooders. Our findings support the hypothesis that ruminative thinking interferes with the search for specific memories while facilitating the uncontrolled retrieval of negatively biased self-schemes. The observed neurobehavioral dysfunctions might put older people with brooding tendency at high risk for becoming depressed when reviewing their past. Training of autobiographical memory ability might therefore be a promising approach to increase resilience against depression in late-life. PMID:27695414

  12. Brooding Is Related to Neural Alterations during Autobiographical Memory Retrieval in Aging

    PubMed Central

    Schneider, Sophia; Brassen, Stefanie

    2016-01-01

    Brooding rumination is considered a central aspect of depression in midlife. As older people tend to review their past, rumination tendency might be particularly crucial in late life since it might hinder older adults to adequately evaluate previous events. We scanned 22 non-depressed older adults with varying degrees of brooding tendency with functional magnetic resonance imaging (MRI) while they performed the construction and elaboration of autobiographical memories. Behavioral findings demonstrate that brooders reported lower mood states, needed more time for memory construction and rated their memories as less detailed and less positive. On the neural level, brooding tendency was related to increased amygdala activation during the search for specific memories and reduced engagement of cortical networks during elaboration. Moreover, coupling patterns of the subgenual cingulate cortex with the hippocampus (HC) and the amygdala predicted details and less positive valence of memories in brooders. Our findings support the hypothesis that ruminative thinking interferes with the search for specific memories while facilitating the uncontrolled retrieval of negatively biased self-schemes. The observed neurobehavioral dysfunctions might put older people with brooding tendency at high risk for becoming depressed when reviewing their past. Training of autobiographical memory ability might therefore be a promising approach to increase resilience against depression in late-life.

  13. Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.

    PubMed

    Vanderheyden, William M; George, Sophie A; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R

    2015-08-01

    Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10 Hz) and sigma (10-15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure. PMID:26019008

  14. Sleep Alterations Following Exposure to Stress Predict Fear-Associated Memory Impairments in a Rodent Model of PTSD

    PubMed Central

    Vanderheyden, William M.; George, Sophie A.; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R.

    2015-01-01

    Sleep abnormalities such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of post-traumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating these sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stress exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops in rats. SPS resulted in acutely increased REM sleep, transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. We also report reductions in theta (4–10 Hz) and sigma (10–15 Hz) band power during transition to REM sleep which also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure. PMID:26019008

  15. Modulation of memory, reinforcement and anxiety parameters by intra-amygdala injection of cholecystokinin-fragments Boc-CCK-4 and CCK-8s.

    PubMed

    Huston, J P; Schildein, S; Gerhardt, P; Privou, C; Fink, H; Hasenöhrl, R U

    1998-01-01

    This series of experiments examined the effects of the cholecystokinin (CCK) fragments Boc-CCK-4 and CCK-8s on memory, reinforcement and anxiety following unilateral injection into the central nucleus of the amygdala (CeA). In experiment 1, rats with chronically implanted cannulae were injected with CCK-8s or Boc-CCK-4 and were tested on a one-trial uphill avoidance task. Post-trial injection of 20 ng Boc-CCK-4 or 1 ng CCK-8s was found to improve the retention performance, whereas lower and higher doses had no effect. The hypermnestic effects of Boc-CCK-4 and CCK-8s were no longer evident when injection was performed 5 h, rather than immediately, after the learning trial. In experiment 2, the elevated plus-maze was used to gauge anxiogenous properties of intra-amygdala injections of Boc-CCK-4 and CCK-8s in memory-enhancing doses. The treatment with 20 ng Boc-CCK-4 and 1 ng CCK-8s did not influence the number of entries into and time spent on the open and enclosed arms of the maze as well as other anxiety-related behaviors. In experiment 3, possible reinforcing effects of the CCK-fragments were examined. After intra-amygdala injection of Boc-CCK-4 or CCK-8s in memory-enhancing doses the rats were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. Subsequent tests for conditioned corral preference revealed no evidence for reinforcing or aversive effects of the CCK-fragments. In sum, these findings indicate that Boc-CCK-4 and CCK-8s facilitate memory processing upon injection into the CeA without exerting reinforcing or anxiogenous effects.

  16. Post ischemia intermittent hypoxia induces hippocampal neurogenesis and synaptic alterations and alleviates long-term memory impairment.

    PubMed

    Tsai, Yi-Wei; Yang, Yea-Ru; Sun, Synthia H; Liang, Keng-Chen; Wang, Ray-Yau

    2013-05-01

    Adult hippocampal neurogenesis is important for learning and memory, especially after a brain injury such as ischemia. Newborn hippocampal neurons contribute to memory performance by establishing functional synapses with target cells. This study demonstrated that the maturation of hippocampal neurons is enhanced by postischemia intermittent hypoxia (IH) intervention. The effects of IH intervention in cultured neurons were mediated by increased synaptogenesis, which was primarily regulated by brain-derived neurotrophic factor (BDNF)/PI3K/AKT. Hippocampal neo-neurons expressed BDNF and exhibited enhanced presynaptic function as indicated by increases in the pSynapsin expression, synaptophysin intensity, and postsynapse density following IH intervention after ischemia. Postischemia IH-induced hippocampal neo-neurons were affected by presynaptic activity, which reflected the dynamic plasticity of the glutamatergic receptors. These alterations were also associated with the alleviation of ischemia-induced long-term memory impairment. Our results suggest that postischemia IH intervention rescued ischemia-induced spatial learning and memory impairment by inducing hippocampal neurogenesis and functional synaptogenesis via BDNF expression.

  17. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats

    PubMed Central

    Albores-Garcia, Damaris; Hernandez, Alberto J.; Loera, Miriam J.

    2016-01-01

    Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined. PMID:26885512

  18. Alterations in Memory and Impact on Academic Outcomes in Children Following Allogeneic Hematopoietic Cell Transplantation.

    PubMed

    Lajiness-O'Neill, R; Hoodin, F; Kentor, R; Heinrich, K; Colbert, A; Connelly, J A

    2015-11-01

    The prevalence of late effects following allogeneic hematopoietic cell transplantation (HCT), a curative treatment for pediatric leukemia, is high: 79% of HCT recipients experience chronic medical conditions. The few extant studies of cognitive late effects have focused on intelligence and are equivocal about HCT neurotoxicity. In an archival study of 30 children (mean transplant age = 6 years), we characterize neuropsychological predictors of academic outcomes. Mean intellectual and academic abilities were average, but evidenced extreme variability, particularly on measures of attention and memory: ∼25% of the sample exhibited borderline performance or lower. Medical predictors of outcome revealed paradoxically better memory associated with more severe acute graft-versus-host disease (GVHD) and associated with steroid treatment. Processing speed and memory accounted for 69% and 61% of variance in mathematics and reading outcomes, respectively. Thus, our findings revealed neurocognitive areas of vulnerability in processing speed and memory following HCT that contribute to subsequent academic difficulties. PMID:26319492

  19. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    PubMed

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.

  20. Altered Resting-State Functional Connectivity of the Frontal-Striatal Reward System in Social Anxiety Disorder

    PubMed Central

    Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M.; Hofmann, Stefan G.; Pollack, Mark; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan

    2015-01-01

    We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions. PMID:25928647

  1. Rheumatoid arthritis-associated RBPJ polymorphism alters memory CD4+ T cells.

    PubMed

    Orent, William; Mchenry, Allison R; Rao, Deepak A; White, Charles; Klein, Hans-Ulrich; Bassil, Ribal; Srivastava, Gyan; Replogle, Joseph M; Raj, Towfique; Frangieh, Michael; Cimpean, Maria; Cuerdon, Nicole; Chibnik, Lori; Khoury, Samia J; Karlson, Elizabeth W; Brenner, Michael B; De Jager, Philip; Bradshaw, Elizabeth M; Elyaman, Wassim

    2016-01-15

    Notch signaling has recently emerged as an important regulator of immune responses in autoimmune diseases. The recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional repressor, but converts into a transcriptional activator upon activation of the canonical Notch pathway. Genome-wide association studies of rheumatoid arthritis (RA) identified a susceptibility locus, rs874040(CC), which implicated the RBPJ gene. Here, chromatin state mapping generated using the chromHMM algorithm reveals strong enhancer regions containing DNase I hypersensitive sites overlapping the rs874040 linkage disequilibrium block in human memory, but not in naïve CD4(+) T cells. The rs874040 overlapping this chromatin state was associated with increased RBPJ expression in stimulated memory CD4(+) T cells from healthy subjects homozygous for the risk allele (CC) compared with memory CD4(+) T cells bearing the protective allele (GG). Transcriptomic analysis of rs874040(CC) memory T cells showed a repression of canonical Notch target genes IL (interleukin)-9, IL-17 and interferon (IFN)γ in the basal state. Interestingly, activation of the Notch pathway using soluble Notch ligand, Jagged2-Fc, induced IL-9 and IL-17A while delta-like 4Fc, another Notch ligand, induced higher IFNγ expression in the rs874040(CC) memory CD4(+) T cells compared with their rs874040(GG) counterparts. In RA, RBPJ expression is elevated in memory T cells from RA patients compared with control subjects, and this was associated with induced inflammatory cytokines IL-9, IL-17A and IFNγ in response to Notch ligation in vitro. These findings demonstrate that the rs874040(CC) allele skews memory T cells toward a pro-inflammatory phenotype involving Notch signaling, thus increasing the susceptibility to develop RA. PMID:26604133

  2. The prebiotics 3'Sialyllactose and 6'Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis.

    PubMed

    Tarr, Andrew J; Galley, Jeffrey D; Fisher, Sydney E; Chichlowski, Maciej; Berg, Brian M; Bailey, Michael T

    2015-11-01

    There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3'Sialyllactose (3'SL) or 6'Sialyllactose (6'SL) for 2 weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3'SL or 6'SL. In addition, 3'SL and 6'SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis.

  3. GABAergic alterations in neocortex of patients with pharmacoresistant temporal lobe epilepsy can explain the comorbidity of anxiety and depression: the potential impact of clinical factors.

    PubMed

    Rocha, Luisa; Alonso-Vanegas, Mario; Martínez-Juárez, Iris E; Orozco-Suárez, Sandra; Escalante-Santiago, David; Feria-Romero, Iris Angélica; Zavala-Tecuapetla, Cecilia; Cisneros-Franco, José Miguel; Buentello-García, Ricardo Masao; Cienfuegos, Jesús

    2014-01-01

    Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1-6, β1-3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.

  4. GABAergic Alterations in Neocortex of Patients with Pharmacoresistant Temporal Lobe Epilepsy Can Explain the Comorbidity of Anxiety and Depression: The Potential Impact of Clinical Factors

    PubMed Central

    Rocha, Luisa; Alonso-Vanegas, Mario; Martínez-Juárez, Iris E.; Orozco-Suárez, Sandra; Escalante-Santiago, David; Feria-Romero, Iris Angélica; Zavala-Tecuapetla, Cecilia; Cisneros-Franco, José Miguel; Buentello-García, Ricardo Masao; Cienfuegos, Jesús

    2015-01-01

    Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1–6, β1–3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness. PMID:25601827

  5. Gray Matter Alterations in Post-Traumatic Stress Disorder, Obsessive-Compulsive Disorder, and Social Anxiety Disorder.

    PubMed

    Cheng, Bochao; Huang, Xiaoqi; Li, Shiguang; Hu, Xinyu; Luo, Ya; Wang, Xiuli; Yang, Xun; Qiu, Changjian; Yang, Yanchun; Zhang, Wei; Bi, Feng; Roberts, Neil; Gong, Qiyong

    2015-01-01

    Post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI. PMID:26347628

  6. Gray Matter Alterations in Post-Traumatic Stress Disorder, Obsessive–Compulsive Disorder, and Social Anxiety Disorder

    PubMed Central

    Cheng, Bochao; Huang, Xiaoqi; Li, Shiguang; Hu, Xinyu; Luo, Ya; Wang, Xiuli; Yang, Xun; Qiu, Changjian; Yang, Yanchun; Zhang, Wei; Bi, Feng; Roberts, Neil; Gong, Qiyong

    2015-01-01

    Post-traumatic stress disorder (PTSD), obsessive–compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI. PMID:26347628

  7. GPER1 (GPR30) knockout mice display reduced anxiety and altered stress response in a sex and paradigm dependent manner

    PubMed Central

    Kastenberger, Iris; Schwarzer, Christoph

    2014-01-01

    The putative estrogen receptor GPER1 (the former orphan receptor GPR30) is discussed to be involved in emotional and cognitive functions and stress control. We recently described the induction of anxiety-like effects by the GPER1 agonist G-1 upon systemic injection into mice. To contribute to a better understanding of the role of GPER1 in anxiety and stress, we investigated germ-line GPER1 deficient mice. Our experiments revealed marked differences between the sexes. A mild but consistent phenotype of increased exploratory drive was observed in the home cage, the elevated plus maze and the light–dark choice test in male GPER1 KO mice. In contrast, female GPER1-KO mice displayed a less pronounced phenotype in these tests. Estrous-stage dependent mild anxiolytic-like effects were observed solely in the open field test. Notably, we observed a strong shift in acute stress coping behavior in the tail suspension test and basal corticosterone levels in different phases of the estrous cycle in female GPER1-KO mice. Our data, in line with previous reports, suggest that GPER1 is involved in anxiety and stress control. Surprisingly, its effects appear to be stronger in male than female mice. PMID:25236887

  8. Sex-specific disruptions in spatial memory and anhedonia in a "two hit" rat model correspond with alterations in hippocampal brain-derived neurotrophic factor expression and signaling.

    PubMed

    Hill, Rachel A; Klug, Maren; Kiss Von Soly, Szerenke; Binder, Michele D; Hannan, Anthony J; van den Buuse, Maarten

    2014-10-01

    Post-mortem studies have demonstrated reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of schizophrenia and major depression patients. The "two hit" hypothesis proposes that two or more major disruptions at specific time points during development are involved in the pathophysiology of these mental illnesses. However, the role of BDNF in these "two hit" effects is unclear. Our aim was to behaviorally characterize a "two hit" rat model of developmental stress accompanied by an in-depth assessment of BDNF expression and signalling. Wistar rats were exposed to neonatal maternal separation (MS) stress and/or adolescent/young-adult corticosterone (CORT) treatment. In adulthood, models of cognitive and negative symptoms of mental illness were analyzed. The hippocampus was then dissected into dorsal (DHP) and ventral (VHP) regions and analyzed by qPCR for exon-specific BDNF gene expression or by Western blot for BDNF protein expression and downstream signaling. Male "two hit" rats showed marked disruptions in short-term spatial memory (Y-maze) which were absent in females. However, female "two hit" rats showed signs of anhedonia (sucrose preference test), which were absent in males. Novel object recognition and anxiety (elevated plus maze) were unchanged by either of the two "hits". In the DHP, MS caused a male-specific increase in BDNF Exons I, II, IV, VII, and IX mRNA but a decrease in mature BDNF and phosphorylated TrkB (pTrkB) protein expression in adulthood. In the VHP, BDNF transcript expression was unchanged; however, in female rats only, MS significantly decreased mature BDNF and pTrkB protein expression in adulthood. These data demonstrate that MS causes region-specific and sex-specific long-term effects on BDNF expression and signaling and, importantly, mRNA expression does not always infer protein expression. Alterations to BDNF signaling may mediate the sex-specific effects of developmental stress on anhedonic behaviors.

  9. Cocaine Self-Administration Alters the Relative Effectiveness of Multiple Memory Systems during Extinction

    ERIC Educational Resources Information Center

    Gabriele, Amanda; Setlow, Barry; Packard, Mark G.

    2009-01-01

    Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable "habit" and "cognitive" memory systems, respectively. In the response extinction condition, rats performed a runway approach response…

  10. Electrophysiological Evidence of Altered Memory Processing in Children Experiencing Early Deprivation

    ERIC Educational Resources Information Center

    Guler, O. Evren; Hostinar, Camelia E.; Frenn, Kristin A.; Nelson, Charles A.; Gunnar, Megan R.; Thomas, Kathleen M.

    2012-01-01

    Associations between early deprivation and memory functioning were examined in 9- to 11-year-old children. Children who had experienced prolonged institutional care prior to adoption were compared to children who were adopted early from foster care and children reared in birth families. Measures included the Paired Associates Learning task from…

  11. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    PubMed Central

    Underwood, Erica L.; Thompson, Lucien T.

    2016-01-01

    While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD) on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD) for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms. PMID:26819773

  12. Short-term total sleep deprivation alters delay-conditioned memory in the rat.

    PubMed

    Tripathi, Shweta; Jha, Sushil K

    2016-06-01

    Short-term sleep deprivation soon after training may impair memory consolidation. Also, a particular sleep stage or its components increase after learning some tasks, such as negative and positive reinforcement tasks, avoidance tasks, and spatial learning tasks, and so forth. It suggests that discrete memory types may require specific sleep stage or its components for their optimal processing. The classical conditioning paradigms are widely used to study learning and memory but the role of sleep in a complex conditioned learning is unclear. Here, we have investigated the effects of short-term sleep deprivation on the consolidation of delay-conditioned memory and the changes in sleep architecture after conditioning. Rats were trained for the delay-conditioned task (for conditioning, house-light [conditioned stimulus] was paired with fruit juice [unconditioned stimulus]). Animals were divided into 3 groups: (a) sleep deprived (SD); (b) nonsleep deprived (NSD); and (c) stress control (SC) groups. Two-way ANOVA revealed a significant interaction between groups and days (training and testing) during the conditioned stimulus-unconditioned stimulus presentation. Further, Tukey post hoc comparison revealed that the NSD and SC animals exhibited significant increase in performances during testing. The SD animals, however, performed significantly less during testing. Further, we observed that wakefulness and NREM sleep did not change after training and testing. Interestingly, REM sleep increased significantly on both days compared to baseline more specifically during the initial 4-hr time window after conditioning. Our results suggest that the consolidation of delay-conditioned memory is sleep-dependent and requires augmented REM sleep during an explicit time window soon after training. (PsycINFO Database Record PMID:26890247

  13. Frequency-Dependent Brain Regional Homogeneity Alterations in Patients with Mild Cognitive Impairment during Working Memory State Relative to Resting State.

    PubMed

    Wang, Pengyun; Li, Rui; Yu, Jing; Huang, Zirui; Li, Juan

    2016-01-01

    Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI). However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control (NC) subjects. Therefore, using the index of regional homogeneity (ReHo), we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex (PCC) in the slow-3 band (0.073-0.198 Hz), and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex (PFC), the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01-0.027 Hz). Furthermore, in NCs, the value of ReHo in clusters belonging to the default mode network (DMN) decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients. This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states. PMID:27047375

  14. Frequency-Dependent Brain Regional Homogeneity Alterations in Patients with Mild Cognitive Impairment during Working Memory State Relative to Resting State

    PubMed Central

    Wang, Pengyun; Li, Rui; Yu, Jing; Huang, Zirui; Li, Juan

    2016-01-01

    Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI). However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control (NC) subjects. Therefore, using the index of regional homogeneity (ReHo), we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex (PCC) in the slow-3 band (0.073–0.198 Hz), and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex (PFC), the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01–0.027 Hz). Furthermore, in NCs, the value of ReHo in clusters belonging to the default mode network (DMN) decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients. This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states. PMID:27047375

  15. Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice.

    PubMed

    Clark, Jason K; Furgerson, Matthew; Crystal, Jonathon D; Fechheimer, Marcus; Furukawa, Ruth; Wagner, John J

    2015-11-01

    Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3month old) 3xTg-AD mice were as impaired in the spatial working memory task as the older (8month old) 3xTg-AD mice when compared with age-matched NonTg control animals. Field potential recordings from the CA1 region of slices prepared from the ventral hippocampus were obtained to assess synaptic transmission and capability for synaptic plasticity. At 3months of age, the NMDA receptor-dependent component of LTP was reduced in 3xTg-AD mice. However, the magnitude of the non-NMDA receptor-dependent component of LTP was concomitantly increased, resulting in a similar amount of total LTP in 3xTg-AD and NonTg mice. At 8months of age, the NMDA receptor-dependent LTP was again reduced in 3xTg-AD mice, but now the non-NMDA receptor-dependent component was decreased as well, resulting in a significantly reduced total amount of LTP in 3xTg-AD compared with NonTg mice. Both 3 and 8month old 3xTg-AD mice exhibited reductions in paired-pulse facilitation and NMDA receptor-dependent LTP that coincided with the deficit in spatial working memory. The early presence of this cognitive impairment and the associated alterations in synaptic plasticity demonstrate that the onset of some behavioral and neurophysiological consequences can occur before the detectable presence of plaques and tangles in the 3xTg-AD mouse model of Alzheimer's disease.

  16. Spatial memory alterations in children with epilepsy of genetic origin or unknown cause.

    PubMed

    Cimadevilla, José Manuel; Lizana, Julio Ramos; Roldán, Maria Dolores; Cánovas, Rosa; Rodríguez, Eva

    2014-06-01

    Genetic generalised epilepsy or epilepsy of unknown cause can remit before adolescence. In many children, the disease does not interfere with their academic achievement. Although there are neuropsychological studies characterising the cognitive profile, there are no studies in this population focused on spatial orientation abilities. In this study, we compared children with genetic generalised epilepsy or epilepsy of unknown cause with a control group using a virtual spatial learning task. Children with epilepsy showed worse performance on the spatial orientation task, although their visuo-spatial memory, attention, and working memory were normal. These results confirm that genetic generalised epilepsy or epilepsy of unknown cause is associated with more cognitive deficits. Virtual reality technologies can complement clinical assessment.

  17. Metformin treatment alters memory function in a mouse model of Alzheimer's disease.

    PubMed

    DiTacchio, Kacee A; Heinemann, Stephen F; Dziewczapolski, Gustavo

    2015-01-01

    Metabolic dysfunction exacerbates Alzheimer's disease (AD) incidence and progression. Here we report that activation of the AMPK pathway, a common target in the management of diabetes, results in gender-divergent cognitive effects in a murine model of the disease. Specifically, our results show that activation of AMPK increases memory dysfunction in males but is protective in females, suggesting that gender considerations may constitute an important factor in medical intervention of diabetes as well as AD.

  18. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    ERIC Educational Resources Information Center

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  19. Manipulating letter fluency for words alters electrophysiological correlates of recognition memory

    PubMed Central

    Lucas, Heather D.; Paller, Ken A.

    2013-01-01

    The mechanisms that give rise to familiarity memory have received intense research interest. One current topic of debate concerns the extent to which familiarity is driven by the same fluency sources that give rise to certain implicit memory phenomena. Familiarity may be tied to conceptual fluency, given that familiarity and conceptual implicit memory can exhibit similar neurocognitive properties. However, familiarity can also be driven by perceptual factors, and its neural basis under these circumstances has received less attention. Here we recorded brain potentials during recognition testing using a procedure that has previously been shown to encourage a reliance on letter information when assessing familiarity for words. Studied and unstudied words were derived either from two separate letter pools or a single letter pool (“letter-segregated” and “normal” conditions, respectively) in a within-subjects contrast. As predicted, recognition accuracy was higher in the letter-segregated relative to the normal condition. Electrophysiological analyses revealed parietal old-new effects from 500–700 ms in both conditions. In addition, a topographically dissociable occipital old-new effect from 300–700 ms was present in the letter-segregated condition only. In a second experiment, we found that similar occipital brain potentials were associated with confident false recognition of words that shared letters with studied words but were not themselves studied. These findings indicate that familiarity is a multiply determined phenomenon, and that the stimulus dimensions on which familiarity is based can moderate its neural correlates. Conceptual and perceptual contributions to familiarity vary across testing circumstances, and both must be accounted for in theories of recognition memory and its neural basis. PMID:23871869

  20. Suppression of inhibitory GABAergic transmission by cAMP signaling pathway: alterations in learning and memory mutants

    PubMed Central

    Ganguly, Archan; Lee, Daewoo

    2013-01-01

    The cAMP signaling pathway mediates synaptic plasticity and is essential for memory formation in both vertebrate and invertebrates. In the fruit fly Drosophila melanogaster, mutations in the cAMP pathway lead to impaired olfactory learning. These mutant genes are preferentially expressed in the mushroom body (MB), an anatomical structure essential for learning. While cAMP-mediated synaptic plasticity is known to be involved in facilitation at the excitatory synapses, little is known about its function in GABAergic synaptic plasticity and learning. In this study, using whole-cell patch clamp technique on Drosophila primary neuronal cultures, we demonstrate that focal application of an adenylate cyclase activator forskolin (FSK) suppresses inhibitory GABAergic postsynaptic currents (IPSCs). We observed a dual regulatory role of FSK on GABAergic transmission, where it increases overall excitability at GABAergic synapses, while simultaneously acting on postsynaptic GABA receptors to suppress GABAergic IPSCs. Further we show that cAMP decreases GABAergic IPSCs in a PKA-dependent manner through a postsynaptic mechanism. PKA acts through the modulation of ionotropic GABA receptor sensitivity to the neurotransmitter GABA. This regulation of GABAergic IPSCs is altered in the cAMP pathway and short-term memory mutants dunce and rutabaga, with both showing altered GABA receptor sensitivity. Interestingly, this effect is also conserved in the MB neurons of both these mutants. Thus, our study suggests that alterations of cAMP-mediated GABAergic plasticity, particularly in the MB neurons of cAMP mutants, account for their defects in olfactory learning. PMID:23387411

  1. Sulforaphane rescues memory dysfunction and synaptic and mitochondrial alterations induced by brain iron accumulation.

    PubMed

    Lavich, I C; de Freitas, B S; Kist, L W; Falavigna, L; Dargél, V A; Köbe, L M; Aguzzoli, C; Piffero, B; Florian, P Z; Bogo, M R; de Lima, M N M; Schröder, N

    2015-08-20

    Iron overload contributes to the development of neurodegeneration and the exacerbation of normal apoptosis rates, largely due to its participation in the Fenton reaction and production of reactive oxygen species (ROS). Mitochondria constitute the major intracellular source of ROS and the main target of attack by free radicals. They are dynamic organelles that bind (fusion) and divide (fission) in response to environmental stimuli, developmental status, and energy needs of the cells. Sulforaphane (SFN) is a natural compound that displays antioxidant and anti-inflammatory activities. This study aims to investigate the effects of SFN on memory deficits and changes in markers of mitochondrial function, DNM1L and OPA1, and the synaptic marker, synaptophysin, induced by neonatal iron treatment. Male rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. In adulthood, they were treated with saline or SFN (0.5 or 5mg/kg) for 14days every other day. Memory deficits were assessed using the object recognition task. DNM1L, OPA1, and synaptophysin levels in the hippocampus were quantified by Western blotting. Results showed that SFN was able to reverse iron-induced decreases in mitochondrial fission protein, DNM1L, as well as synaptophysin levels in the hippocampus, leading to a recovery of recognition memory impairment induced by iron. These findings suggest that SFN may be further investigated as potential agent for the treatment of cognitive deficits associated with neurodegenerative disorders.

  2. Embryonic GABA(B) receptor blockade alters cell migration, adult hypothalamic structure, and anxiety- and depression-like behaviors sex specifically in mice.

    PubMed

    Stratton, Matthew S; Staros, Michelle; Budefeld, Tomaz; Searcy, Brian T; Nash, Connor; Eitel, Chad; Carbone, David; Handa, Robert J; Majdic, Gregor; Tobet, Stuart A

    2014-01-01

    Neurons of the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic- pituitary-adrenal (HPA) axis and the autonomic nervous system. Females lacking functional GABA(B) receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABA(B) receptor to a 7-day critical period (E11-E17) during embryonic development. Experiments tested the role of GABA(B) receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABA(B) receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABA(B) receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABA(B) receptor antagonist. Embryonic exposure to GABA(B) receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABA(B) receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity.

  3. Embryonic GABAB Receptor Blockade Alters Cell Migration, Adult Hypothalamic Structure, and Anxiety- and Depression-Like Behaviors Sex Specifically in Mice

    PubMed Central

    Stratton, Matthew S.; Staros, Michelle; Budefeld, Tomaz; Searcy, Brian T.; Nash, Connor; Eitel, Chad; Carbone, David; Handa, Robert J.; Majdic, Gregor; Tobet, Stuart A.

    2014-01-01

    Neurons of the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic- pituitary-adrenal (HPA) axis and the autonomic nervous system. Females lacking functional GABAB receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABAB receptor to a 7-day critical period (E11–E17) during embryonic development. Experiments tested the role of GABAB receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABAB receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABAB receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABAB receptor antagonist. Embryonic exposure to GABAB receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABAB receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity. PMID:25162235

  4. A Quasi-Experimental Study Investigating the Effect of Scent on Students' Memory of Multiplication Facts and Math Anxiety

    ERIC Educational Resources Information Center

    Leap, Evelyn M.

    2013-01-01

    This quasi-experimental study was conducted with two fifth grade classrooms to investigate the effect of scent on students' acquisition and retention of multiplication facts and math anxiety. Forty participants received daily instruction for nine weeks, using a strategy-rich multiplication program called Factivation. Students in the Double Smencil…

  5. Maternal protein restriction in the rat during pregnancy and/or lactation alters cognitive and anxiety behaviors of female offspring.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Charco, R; Bautista, C J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2012-02-01

    Maternal protein deficiencies can developmentally program offspring to lifelong dysfunction of many physiological systems. We hypothesized that maternal isocaloric low protein diet during fetal and early postnatal development would negatively affect female offspring anxiety, exploration, associative learning and motivation as measured by the elevated plus maze (EPM), open field test (OFT), operant conditioning and the progressive ratio task, respectively. Control mothers (C) received a 20% casein diet and restricted mothers (R) a 10% casein diet to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second lactation diet) to enable evaluation of offspring effects influenced by maternal diet during pregnancy and lactation. Maternal protein restriction decreased open arm time and distance in RR and RC offspring, increased anxiety behavior, in the EPM. In the OFT, the RR and RC offspring displayed decreased exploration (increased stress) as indexed by decreased distance in the center zone. These behaviors in the EPM and OFT was associated with increased corticosterone levels during an immobilization test in the RR offspring with intermediary effects in the RC offspring. Learning impairment was observed in the RR, CR and RC offspring during fixed ratio 5 schedule of reinforcement. Motivational effects were measured in RR offspring responding less, decreased motivation, and CR offspring making more responses, increased motivation, than CC offspring. These findings reveal the negative effects of developmental protein restriction on female offspring behavior. The underlying basis for these negative outcomes remains to be elucidated.

  6. Perfusion Deficits and Functional Connectivity Alterations in Memory-Related Regions of Patients with Post-Traumatic Stress Disorder.

    PubMed

    Liu, Yang; Li, Baojuan; Feng, Na; Pu, Huangsheng; Zhang, Xi; Lu, Hongbing; Yin, Hong

    2016-01-01

    To explore the potential alterations in cerebral blood flow (CBF) and functional connectivity of recent onset post-traumatic stress disorder (PTSD) induced by a single prolonged trauma exposure, we recruited 20 survivors experiencing the same coal mining flood disaster as the PTSD (n = 10) and non-PTSD (n = 10) group, respectively. The pulsed arterial spin labeling (ASL) images were acquired with a 3.0T MRI scanner and the partial volume (PV) effect in the images was corrected for better CBF estimation. Alterations in CBF were analyzed using both uncorrected and PV-corrected CBF maps. By using altered CBF regions as regions-of-interest, seed-based functional connectivity analysis was then performed. While only one CBF deficit in right corpus callosum of PTSD patients was detected using uncorrected CBF, three more regions (bilateral frontal lobes and right superior frontal gyrus) were identified using PV-corrected CBF. Furthermore, the regional CBF of right superior frontal gyrus exhibited significantly negative correlation with the symptom severity (r = -0.759, p = 0.018). The resting-state functional connectivity analysis revealed increased connectivity between left frontal lobe and right parietal lobe. The results indicated the symptom-specific perfusion deficits and an aberrant connectivity in memory-related regions of PTSD patients when using PV-corrected ASL data. It also suggested that PV-corrected CBF exhibits more subtle changes that may be beneficial to perfusion and connectivity analysis. PMID:27213610

  7. Perfusion Deficits and Functional Connectivity Alterations in Memory-Related Regions of Patients with Post-Traumatic Stress Disorder

    PubMed Central

    Feng, Na; Pu, Huangsheng; Zhang, Xi; Lu, Hongbing; Yin, Hong

    2016-01-01

    To explore the potential alterations in cerebral blood flow (CBF) and functional connectivity of recent onset post-traumatic stress disorder (PTSD) induced by a single prolonged trauma exposure, we recruited 20 survivors experiencing the same coal mining flood disaster as the PTSD (n = 10) and non-PTSD (n = 10) group, respectively. The pulsed arterial spin labeling (ASL) images were acquired with a 3.0T MRI scanner and the partial volume (PV) effect in the images was corrected for better CBF estimation. Alterations in CBF were analyzed using both uncorrected and PV-corrected CBF maps. By using altered CBF regions as regions-of-interest, seed-based functional connectivity analysis was then performed. While only one CBF deficit in right corpus callosum of PTSD patients was detected using uncorrected CBF, three more regions (bilateral frontal lobes and right superior frontal gyrus) were identified using PV-corrected CBF. Furthermore, the regional CBF of right superior frontal gyrus exhibited significantly negative correlation with the symptom severity (r = −0.759, p = 0.018). The resting-state functional connectivity analysis revealed increased connectivity between left frontal lobe and right parietal lobe. The results indicated the symptom-specific perfusion deficits and an aberrant connectivity in memory-related regions of PTSD patients when using PV-corrected ASL data. It also suggested that PV-corrected CBF exhibits more subtle changes that may be beneficial to perfusion and connectivity analysis. PMID:27213610

  8. [Interindividual differences in priming and memory effects of threatening stimuli: effect of cognitive avoidance and vigilant anxiety coping].

    PubMed

    Hock, M; Egloff, B

    1998-01-01

    This study examined the influence of dispositional coping strategies (cognitive avoidance, vigilance) on priming and memory effects of emotional stimuli. In the first phase of the study participants performed a lexical decision task that involved threat-related and neutral words. Subsequently, a previously unannounced recognition memory test for a subset of the words presented during the first phase was carried out. Repressers (i.e. individuals high in avoidance and low in vigilance) showed stronger emotional priming effects than nonavoiders. Repressers also showed a memory deficit for emotional relative to neutral words, whereas sensitizers (vigilance high, avoidance low) remembered emotional words comparatively well. Results raise the question of whether repressers' memory deficits for threat-related stimuli are actually based on a less differentiated network of emotional information, as assumed by recent theoretical accounts of individual differences in coping.

  9. ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

    PubMed Central

    2013-01-01

    Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

  10. Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome.

    PubMed

    Hansen, Katelin F; Sakamoto, Kensuke; Aten, Sydney; Snider, Kaitlin H; Loeser, Jacob; Hesse, Andrea M; Page, Chloe E; Pelz, Carl; Arthur, J Simon C; Impey, Soren; Obrietan, Karl

    2016-02-01

    miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in

  11. Differential effectiveness of tianeptine, clonidine and amitriptyline in blocking traumatic memory expression, anxiety and hypertension in an animal model of PTSD.

    PubMed

    Zoladz, Phillip R; Fleshner, Monika; Diamond, David M

    2013-07-01

    Individuals exposed to life-threatening trauma are at risk for developing post-traumatic stress disorder (PTSD), a debilitating condition that involves persistent anxiety, intrusive memories and several physiological disturbances. Current pharmacotherapies for PTSD manage only a subset of these symptoms and typically have adverse side effects which limit their overall effectiveness. We evaluated the effectiveness of three different pharmacological agents to ameliorate a broad range of PTSD-like symptoms in our established predator-based animal model of PTSD. Adult male Sprague-Dawley rats were given 1-h cat exposures on two occasions that were separated by 10 days, in conjunction with chronic social instability. Beginning 24 h after the first cat exposure, rats received daily injections of amitriptyline, clonidine, tianeptine or vehicle. Three weeks after the second cat exposure, all rats underwent a battery of behavioral and physiological tests. The vehicle-treated, psychosocially stressed rats demonstrated a robust fear memory for the two cat exposures, as well as increased anxiety expressed on the elevated plus maze, an exaggerated startle response, elevated heart rate and blood pressure, reduced growth rate and increased adrenal gland weight, relative to the vehicle-treated, non-stressed (control) rats. Neither amitriptyline nor clonidine was effective at blocking the entire cluster of stress-induced sequelae, and each agent produced adverse side effects in control subjects. Only the antidepressant tianeptine completely blocked the effects of psychosocial stress on all of the physiological and behavioral measures that were examined. These findings illustrate the differential effectiveness of these three treatments to block components of PTSD-like symptoms in rats, and in particular, reveal the profile of tianeptine as the most effective of all three agents.

  12. Role of NPY Y1 receptor on acquisition, consolidation and extinction on contextual fear conditioning: dissociation between anxiety, locomotion and non-emotional memory behavior.

    PubMed

    Lach, Gilliard; de Lima, Thereza Christina Monteiro

    2013-07-01

    Neuropeptide Y (NPY) is the most abundant peptide in the central nervous system (CNS) and is densely localized in the brain regions involved in stress, memory, fear and anxiety. Although previous research supports a role for NPY in the mediation of rodent and human emotional behavior, there is currently a lack of information on the effects of low doses of NPY that could have a potential therapeutic advantage, minimizing side-effects such as cognition impairment or sedation. Herein, we assessed the effects of intracerebroventricular (i.c.v.) administration of low doses of NPY, and of the Y1-agonist Leu31Pro34-NPY (LP-NPY) on contextual fear conditioning (CFC), as they have no effect on unconditioned anxiety-like, locomotor activity and non-emotional memory. NPY (3 pmol) and LP-NPY (1 pmol) inhibited freezing behavior when administered in the acquisition or consolidation stages, indicating a reduction of fear. When injected in the extinction phase, only NPY inhibited freezing behavior on CFC. Pre-treatment with the Y1-antagonist BIBO3304 before NPY and LP-NPY was able to prevent the inhibition of fear responses induced by both NPY agonists. Taken together, our results demonstrate robust fear-inhibiting effects of i.c.v. injection of NPY on contextual fear conditioning in rats, a response that is mediated, at least in part, by the Y1 receptor. Moreover, these treatments were unable to change locomotor activity or to show an anxiolytic-like effect, as evaluated in an open-field and an elevated plus-maze. This specific fear reduction effect may underlie resilience systems in the CNS and has potential therapeutic relevance in PTSD.

  13. Differential effectiveness of tianeptine, clonidine and amitriptyline in blocking traumatic memory expression, anxiety and hypertension in an animal model of PTSD.

    PubMed

    Zoladz, Phillip R; Fleshner, Monika; Diamond, David M

    2013-07-01

    Individuals exposed to life-threatening trauma are at risk for developing post-traumatic stress disorder (PTSD), a debilitating condition that involves persistent anxiety, intrusive memories and several physiological disturbances. Current pharmacotherapies for PTSD manage only a subset of these symptoms and typically have adverse side effects which limit their overall effectiveness. We evaluated the effectiveness of three different pharmacological agents to ameliorate a broad range of PTSD-like symptoms in our established predator-based animal model of PTSD. Adult male Sprague-Dawley rats were given 1-h cat exposures on two occasions that were separated by 10 days, in conjunction with chronic social instability. Beginning 24 h after the first cat exposure, rats received daily injections of amitriptyline, clonidine, tianeptine or vehicle. Three weeks after the second cat exposure, all rats underwent a battery of behavioral and physiological tests. The vehicle-treated, psychosocially stressed rats demonstrated a robust fear memory for the two cat exposures, as well as increased anxiety expressed on the elevated plus maze, an exaggerated startle response, elevated heart rate and blood pressure, reduced growth rate and increased adrenal gland weight, relative to the vehicle-treated, non-stressed (control) rats. Neither amitriptyline nor clonidine was effective at blocking the entire cluster of stress-induced sequelae, and each agent produced adverse side effects in control subjects. Only the antidepressant tianeptine completely blocked the effects of psychosocial stress on all of the physiological and behavioral measures that were examined. These findings illustrate the differential effectiveness of these three treatments to block components of PTSD-like symptoms in rats, and in particular, reveal the profile of tianeptine as the most effective of all three agents. PMID:23318688

  14. Looking beyond Fear and Extinction Learning: Considering Novel Treatment Targets for Anxiety

    PubMed Central

    Britton, Jennifer C.; Evans, Travis C.; Hernandez, Michael V.

    2014-01-01

    Fear conditioning studies provide valuable insight into how fears are learned and extinguished. Previous work focuses on fear and extinction learning to understand and treat anxiety disorders. However, a cascade of cognitive processes that extend beyond learning may also yield therapeutic targets for anxiety disorders. Throughout this review, we will discuss recent findings of fear generalization, memory consolidation, and reconsolidation. Factors related to effectiveness, efficiency and durability of extinction-based treatments will be addressed. Moreover, adolescence may be a key developmental stage when threat-related perturbations emerge; therefore, targeting interventions during adolescence when these nascent processes are more malleable may alter the trajectory of anxiety disorders. PMID:25705579

  15. Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

    PubMed Central

    Winkle, Cortney C.; Olsen, Reid H. J.; Kim, Hyojin; Moy, Sheryl S.

    2016-01-01

    During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9−/− adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9−/− mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. SIGNIFICANCE STATEMENT Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo. Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo. These cellular defects were associated with severe deficits in spatial learning and memory. PMID:27147649

  16. Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood.

    PubMed

    McCormick, Cheryl M; Thomas, Catherine M; Sheridan, Cheryl S; Nixon, Feather; Flynn, Jennifer A; Mathews, Iva Z

    2012-06-01

    The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

  17. Multiple effects of circadian dysfunction induced by photoperiod shifts: alterations in context memory and food metabolism in the same subjects.

    PubMed

    McDonald, Robert J; Zelinski, Erin L; Keeley, Robin J; Sutherland, Dylan; Fehr, Leah; Hong, Nancy S

    2013-06-13

    Humans exposed to shiftwork conditions have been reported to have increased susceptibility to various health problems including various forms of dementia, cancer, heart disease, and metabolic disorders related to obesity. The present experiments assessed the effects of circadian disruption on learning and memory function and various food related processes including diet consumption rates, food metabolism, and changes in body weight. These experiments utilized a novel variant of the conditioned place preference task (CPP) that is normally used to assess Pavlovian associative learning and memory processes produced via repeated context-reward pairings. For the present experiments, the standard CPP paradigm was modified in that both contexts were paired with food, but the dietary constituents of the food were different. In particular, we were interested in whether rats could differentiate between two types of carbohydrates, simple (dextrose) and complex (starch). Consumption rates for each type of carbohydrate were measured throughout training. A test of context preference without the food present was also conducted. At the end of behavioral testing, a fasting glucose test and a glucose challenge test were administered. Chronic photoperiod shifting resulted in impaired context learning and memory processes thought to be mediated by a neural circuit centered on the hippocampus. The results also showed that preferences for the different carbohydrate diets were altered in rats experiencing photoperiod shifting in that they maintained an initial preference for the simple carbohydrate throughout training. Lastly, photoperiod shifting resulted in changes in fasting blood glucose levels and elicited weight gain. These results show that chronic photoperiod shifting, which likely resulted in circadian dysfunction, impairs multiple functions of the brain and/or body in the same individual. PMID:23660277

  18. Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance, enhanced rearing, and spatial memory deficit.

    PubMed

    Lee, Jiseok; Chung, Changuk; Ha, Seungmin; Lee, Dongmin; Kim, Do-Young; Kim, Hyun; Kim, Eunjoon

    2015-01-01

    Shank3 is a postsynaptic scaffolding protein implicated in synapse development and autism spectrum disorders. The Shank3 gene is known to produce diverse splice variants whose functions have not been fully explored. In the present study, we generated mice lacking Shank3 exon 9 (Shank3 (Δ9) mice), and thus missing five out of 10 known Shank3 splice variants containing the N-terminal ankyrin repeat region, including the longest splice variant, Shank3a. Our X-gal staining results revealed that Shank3 proteins encoded by exon 9-containing splice variants are abundant in upper cortical layers, striatum, hippocampus, and thalamus, but not in the olfactory bulb or cerebellum, despite the significant Shank3 mRNA levels in these regions. The hippocampal CA1 region of Shank3 (Δ9) mice exhibited reduced excitatory transmission at Schaffer collateral synapses and increased frequency of spontaneous inhibitory synaptic events in pyramidal neurons. In contrast, prelimbic layer 2/3 pyramidal neurons in the medial prefrontal cortex displayed decreased frequency of spontaneous inhibitory synaptic events, indicating alterations in the ratio of excitation/inhibition (E/I ratio) in the Shank3 (Δ9) brain. These mice displayed a mild increase in rearing in a novel environment and mildly impaired spatial memory, but showed normal social interaction and repetitive behavior. These results suggest that ankyrin repeat-containing Shank3 splice variants are important for E/I balance, rearing behavior, and spatial memory.

  19. CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

    PubMed Central

    Mathew, Roy J.

    1994-01-01

    Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disorders. Possible associations between stress I anxiety I panic and cerebral ischemia I stroke give additional significance to the effects of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR in anxiety disorders became easier. A large numbers of research reports are available on the effects of stress, anxiety and panic on CBF/CMR in normals and anxiety disorder patients. This article reviews the available human research on this topic. PMID:21743685

  20. Reward expectation alters learning and memory: The impact of the amygdala on appetitive-driven behaviors

    PubMed Central

    Savage, Lisa M.; Ramos, Raddy L.

    2009-01-01

    The capacity to seek and obtain rewards is essential for survival. Pavlovian conditioning is one mechanism by which organisms develop predictions about rewards and such anticipatory or expectancy states enable successful behavioral adaptations to environmental demands. Reward expectancies have both affective/motivational and discriminative properties that allow for the modulation of instrumental goal-directed behavior. Recent data provides evidence that different cognitive strategies (cue-outcome associations) and neural systems (amygdala) are used when subjects are trained under conditions that allow Pavlovian-induced reward expectancies to guide instrumental behavioral choices. Furthermore, it has been demonstrated that impairments typically observed in a number of brain-damaged models are alleviated or eliminated by embedding unique reward expectancies into learning/memory tasks. These results suggest that Pavlovian-induced reward expectancies can change both behavioral and brain processes. PMID:19022299

  1. Measures of anxiety, sensorimotor function, and memory in male and female mGluR4-/- mice

    PubMed Central

    Davis, Matthew J.; Haley, Tammie; Duvoisin, Robert M.; Raber, Jacob

    2012-01-01

    Metabotropic glutamate receptors (mGluRs) are coupled to second messenger pathways via G proteins and modulate synaptic transmission. Of the eight different types of mGluRs (mGluR1-mGluR8), mGluR4, mGluR6, mGluR7, and mGluR8 are members of group III. Group III receptors are generally located presynaptically, where they regulate neurotransmitter release. Because of their role in modulating neurotransmission, mGluRs are attractive targets for therapies aimed at treating anxiety disorders. Previously we showed that the mGluR4-selective allosteric agonist VU 0155041 reduces anxiety-like behavior in wild-type male mice. Here, we explore the role of mGluR4 in adult (6-month-old) and middle-aged (12-month-old) male and female mice lacking this receptor. Compared to age- and sex-matched wild-type mice, middle-aged mGluR4-/- male mice showed increased measures of anxiety in the open field and elevated zero maze and impaired sensorimotor function on the rotarod. These changes were not seen in adult 6-month old male mice. In contrast to the male mice, mGluR4-/- female mice showed reduced measures of anxiety in the open field and elevated zero maze and enhanced rotarod performance. During the hidden platform training sessions of the water maze, mGluR4-/-mice swam father away from the platform than wild-type mice at 6, but not at 12, months of age. mGluR4-/- mice also showed enhanced amygdala-dependent cued fear conditioning. No genotype differences were seen in hippocampus-dependent contextual fear conditioning. These data indicate that effects of mGluR4 on sensorimotor function and measures of anxiety, but not cued fear conditioning, are critically modulated by sex and age. PMID:22227508

  2. Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression.

    PubMed

    Darcet, Flavie; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

    2016-03-11

    Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naïve animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD. PMID:26850572

  3. Memories.

    ERIC Educational Resources Information Center

    Brand, Judith, Ed.

    1998-01-01

    This theme issue of the journal "Exploring" covers the topic of "memories" and describes an exhibition at San Francisco's Exploratorium that ran from May 22, 1998 through January 1999 and that contained over 40 hands-on exhibits, demonstrations, artworks, images, sounds, smells, and tastes that demonstrated and depicted the biological,…

  4. Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory.

    PubMed

    Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Fernandez, Francesca; Dinh, Chi H L; Huang, Xu-Feng

    2015-06-01

    High fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood-brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10mg/kg/day BM orally for 21weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF diet-induced impairment in recognition memory (p<0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p<0.05), however, no changes were seen in the hippocampus (p>0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p<0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus.

  5. Brain morphological alterations and cellular metabolic changes in patients with generalized anxiety disorder: A combined DARTEL-based VBM and (1)H-MRS study.

    PubMed

    Moon, Chung-Man; Jeong, Gwang-Woo

    2016-05-01

    Generalized anxiety disorder (GAD) is characterized by emotional dysregulation and cognitive deficit in conjunction with brain morphometric and metabolic alterations. This study assessed the combined neural morphological deficits and metabolic abnormality in patients with GAD. Thirteen patients with GAD and 13 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI and proton magnetic resonance spectroscopy ((1)H-MRS) at 3Tesla. In this study, the combination of voxel-based morphometry (VBM) and (1)H-MRS was used to assess the brain morphometric and metabolic alterations in GAD. The patients showed significantly reduced white matter (WM) volumes in the midbrain (MB), precentral gyrus (PrG), dorsolateral prefrontal cortex (DLPFC) and anterior limb of the internal capsule (ALIC) compared to the controls. In MRS study, the choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC were significantly lower in the patients. Particularly, the WM volume variation of the DLPFC was positively correlated with both of the Cho/Cr and Cho/NAA ratios in patients with GAD. This study provides an evidence for the association between the morphometric deficit and metabolic changes in GAD. This finding would be helpful to understand the neural dysfunction and pathogenesis in connection with cognitive impairments in GAD. PMID:26708039

  6. Brain morphological alterations and cellular metabolic changes in patients with generalized anxiety disorder: A combined DARTEL-based VBM and (1)H-MRS study.

    PubMed

    Moon, Chung-Man; Jeong, Gwang-Woo

    2016-05-01

    Generalized anxiety disorder (GAD) is characterized by emotional dysregulation and cognitive deficit in conjunction with brain morphometric and metabolic alterations. This study assessed the combined neural morphological deficits and metabolic abnormality in patients with GAD. Thirteen patients with GAD and 13 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI and proton magnetic resonance spectroscopy ((1)H-MRS) at 3Tesla. In this study, the combination of voxel-based morphometry (VBM) and (1)H-MRS was used to assess the brain morphometric and metabolic alterations in GAD. The patients showed significantly reduced white matter (WM) volumes in the midbrain (MB), precentral gyrus (PrG), dorsolateral prefrontal cortex (DLPFC) and anterior limb of the internal capsule (ALIC) compared to the controls. In MRS study, the choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC were significantly lower in the patients. Particularly, the WM volume variation of the DLPFC was positively correlated with both of the Cho/Cr and Cho/NAA ratios in patients with GAD. This study provides an evidence for the association between the morphometric deficit and metabolic changes in GAD. This finding would be helpful to understand the neural dysfunction and pathogenesis in connection with cognitive impairments in GAD.

  7. LRRK2 overexpression alters glutamatergic presynaptic plasticity, striatal dopamine tone, postsynaptic signal transduction, motor activity and memory.

    PubMed

    Beccano-Kelly, Dayne A; Volta, Mattia; Munsie, Lise N; Paschall, Sarah A; Tatarnikov, Igor; Co, Kimberley; Chou, Patrick; Cao, Li-Ping; Bergeron, Sabrina; Mitchell, Emma; Han, Heather; Melrose, Heather L; Tapia, Lucia; Raymond, Lynn A; Farrer, Matthew J; Milnerwood, Austen J

    2015-03-01

    Mutations in leucine-rich repeat kinase 2 (Lrrk2) are the most common genetic cause of Parkinson's disease (PD), a neurodegenerative disorder affecting 1-2% of those >65 years old. The neurophysiology of LRRK2 remains largely elusive, although protein loss suggests a role in glutamatergic synapse transmission and overexpression studies show altered dopamine release in aged mice. We show that glutamate transmission is unaltered onto striatal projection neurons (SPNs) of adult LRRK2 knockout mice and that adult animals exhibit no detectable cognitive or motor deficits. Basal synaptic transmission is also unaltered in SPNs of LRRK2 overexpressing mice, but they do exhibit clear alterations to D2-receptor-mediated short-term synaptic plasticity, behavioral hypoactivity and impaired recognition memory. These phenomena are associated with decreased striatal dopamine tone and abnormal dopamine- and cAMP-regulated phosphoprotein 32 kDa signal integration. The data suggest that LRRK2 acts at the nexus of dopamine and glutamate signaling in the adult striatum, where it regulates dopamine levels, presynaptic glutamate release via D2-dependent synaptic plasticity and dopamine-receptor signal transduction. PMID:25343991

  8. LRRK2 overexpression alters glutamatergic presynaptic plasticity, striatal dopamine tone, postsynaptic signal transduction, motor activity and memory.

    PubMed

    Beccano-Kelly, Dayne A; Volta, Mattia; Munsie, Lise N; Paschall, Sarah A; Tatarnikov, Igor; Co, Kimberley; Chou, Patrick; Cao, Li-Ping; Bergeron, Sabrina; Mitchell, Emma; Han, Heather; Melrose, Heather L; Tapia, Lucia; Raymond, Lynn A; Farrer, Matthew J; Milnerwood, Austen J

    2015-03-01

    Mutations in leucine-rich repeat kinase 2 (Lrrk2) are the most common genetic cause of Parkinson's disease (PD), a neurodegenerative disorder affecting 1-2% of those >65 years old. The neurophysiology of LRRK2 remains largely elusive, although protein loss suggests a role in glutamatergic synapse transmission and overexpression studies show altered dopamine release in aged mice. We show that glutamate transmission is unaltered onto striatal projection neurons (SPNs) of adult LRRK2 knockout mice and that adult animals exhibit no detectable cognitive or motor deficits. Basal synaptic transmission is also unaltered in SPNs of LRRK2 overexpressing mice, but they do exhibit clear alterations to D2-receptor-mediated short-term synaptic plasticity, behavioral hypoactivity and impaired recognition memory. These phenomena are associated with decreased striatal dopamine tone and abnormal dopamine- and cAMP-regulated phosphoprotein 32 kDa signal integration. The data suggest that LRRK2 acts at the nexus of dopamine and glutamate signaling in the adult striatum, where it regulates dopamine levels, presynaptic glutamate release via D2-dependent synaptic plasticity and dopamine-receptor signal transduction.

  9. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring

    PubMed Central

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic–pituitary–adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light–dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of

  10. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring.

    PubMed

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic-pituitary-adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light-dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of paternal

  11. Alterations in autobiographical memory for a blast event in OEF/OIF veterans with mild TBI

    PubMed Central

    Palombo, D.J.; Kapson, H.S.; Lafleche, G.; Vasterling, J.J.; Marx, B.P.; Franz, M.; Verfaellie, M.

    2016-01-01

    Objective Although loss of consciousness associated with moderate or severe traumatic brain injury (TBI) is thought to interfere with encoding of the TBI event, little is known about the effects of mild TBI (mTBI), which typically involves only transient disruption in consciousness. Method Blast-exposed Afghanistan and Iraq War veterans were asked to recall the blast event. Participants were stratified based on whether the blast was associated with probable mTBI (n=50) or not (n =25). Narratives were scored for organizational structure (i.e., coherence) using the Narrative Coherence Coding Scheme (Reese et al., 2011) and episodic recollection using the Autobiographical Interview coding procedures (Levine et al., 2002). Results The mTBI group produced narratives that were less coherent but contained more episodic details than those of the no-TBI group. Conclusions These results suggest that mTBI interferes with the organizational quality of memory in a manner that is independent of episodic detail generation. PMID:25893970

  12. Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory.

    PubMed

    Ribeiro, Leandro Rodrigo; Della-Pace, Iuri Domingues; de Oliveira Ferreira, Ana Paula; Funck, Vinícius Rafael; Pinton, Simone; Bobinski, Franciane; de Oliveira, Clarissa Vasconcelos; da Silva Fiorin, Fernando; Duarte, Marta Maria Medeiros Frescura; Furian, Ana Flávia; Oliveira, Mauro Schneider; Nogueira, Cristina Wayne; Dos Santos, Adair Roberto Soares; Royes, Luiz Fernando Freire; Fighera, Michele Rechia

    2013-09-01

    The methylmalonic acidemia is an inborn error of metabolism (IEM) characterized by methylmalonic acid (MMA) accumulation in body fluids and tissues, causing neurological dysfunction, mitochondrial failure and oxidative stress. Although neurological evidence demonstrate that infection and/or inflammation mediators facilitate metabolic crises in patients, the involvement of neuroinflammatory processes in the neuropathology of this organic acidemia is not yet established. In this experimental study, we used newborn Wistar rats to induce a model of chronic acidemia via subcutaneous injections of methylmalonate (MMA, from 5th to 28th day of life, twice a day, ranged from 0.72 to 1.67 μmol/g as a function of animal age). In the following days (29th-31st) animal behavior was assessed in the object exploration test and elevated plus maze. It was performed differential cell and the number of neutrophils counting and interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the blood, as well as levels of IL-1β, TNF-α, inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in the cerebral cortex were measured. Behavioral tests showed that animals injected chronically with MMA have a reduction in the recognition index (R.I.) when the objects were arranged in a new configuration space, but do not exhibit anxiety-like behaviors. The blood of MMA-treated animals showed a decrease in the number of polymorphonuclear and neutrophils, and an increase in mononuclear and other cell types, as well as an increase of IL-1β and TNF-α levels. Concomitantly, MMA increased levels of IL-1β, TNF-α, and expression of iNOS and 3-NT in the cerebral cortex of rats. The overall results indicate that chronic administration of MMA increased pro-inflammatory markers in the cerebral cortex, reduced immune system defenses in blood, and coincide with the behavioral changes found in young rats. This leads to speculate that, through mechanisms not yet elucidated, the

  13. Memory retrieval and its lasting consequences.

    PubMed

    Izquierdo, Iván; Vianna, Mónica R.M.; Izquierdo, Luciana A.; Barros, Daniela M.; Szapiro, Germán; Coitinho, Adriana S.; Muller, Lionel; Cammarota, Martín; Bevilaqua, Lia R.M.; Medina, Jorge H.

    2002-01-01

    Many, if not all psychiatric diseases are accompanied by memory disturbances, in particular, the dementias, schizophrenia, and, to an extent, mood disorders. Anxiety and stress, on the other hand, cause important alterations of memory, particularly its retrieval. Here we discuss several new findings on the basic mechanisms of consolidation, retrieval and extinction of a prototype form of episodic memory in the rat: conditioned fear. The findings point the way for investigations on the pathology of these aspects of memory in health and disease. Emphasis is placed on the parallel processing of retrieval in several cortical areas, on the links between retrieval and the onset of extinction, on the fact that extinction involves new learning requiring gene expression, and on the differences between the retrieval of recent or remote long-term memories.

  14. Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.

    PubMed

    Bhatia, Nitish; Jaggi, Amteshwar Singh; Singh, Nirmal; Anand, Preet; Dhawan, Ravi

    2011-07-01

    The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.

  15. Antisense against Amyloid-β Protein Precursor Reverses Memory Deficits and Alters Gene Expression in Neurotropic and Insulin-Signaling Pathways in SAMP8 Mice.

    PubMed

    Armbrecht, Harvey J; Siddiqui, Akbar M; Green, Michael; Farr, Susan A; Kumar, Vijaya B; Banks, William A; Patrick, Ping; Shah, Gul N; Morley, John E

    2015-01-01

    The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease in memory accompanied by an increase in hippocampal amyloid-β protein precursor (AβPP) and amyloid-β peptide (Aβ). We have shown that administration of an antisense oligonucleotide against the Aβ region of AβPP (AβPP antisense) reverses the memory deficits. The purpose of this study was to determine the effect of peripheral (IV) administration of AβPP antisense on hippocampal gene expression. The AβPP antisense reversed the memory deficits and altered expression of 944 hippocampal genes. Pathway analysis showed significant gene expression changes in nine pathways. These include the MAPK signaling pathway (p = 0.0078) and the phosphatidylinositol signaling pathway (p = 0.043), which we have previously shown to be altered in SAMP8 mice. The changes in these pathways contributed to significant changes in the neurotropin (p = 0.0083) and insulin signaling (p = 0.015) pathways, which are known to be important in learning and memory. Changes in these pathways were accompanied by phosphorylation changes in the downstream target proteins p70S6K, GSK3β, ERK, and CREB. These changes in hippocampal gene expression and protein phosphorylation may suggest specific new targets for antisense therapy aimed at improving memory.

  16. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

    PubMed

    Gericke, G S

    2010-05-01

    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  17. Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence.

    PubMed

    Schweitzer, Julie B; Riggins, Tracy; Liang, Xia; Gallen, Courtney; Kurup, Pradeep K; Ross, Thomas J; Black, Maureen M; Nair, Prasanna; Salmeron, Betty Jo

    2015-01-01

    The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12-15 years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE.

  18. A mid-life vitamin A supplementation prevents age-related spatial memory deficits and hippocampal neurogenesis alterations through CRABP-I.

    PubMed

    Touyarot, Katia; Bonhomme, Damien; Roux, Pascale; Alfos, Serge; Lafenêtre, Pauline; Richard, Emmanuel; Higueret, Paul; Pallet, Véronique

    2013-01-01

    Age-related memory decline including spatial reference memory is considered to begin at middle-age and coincides with reduced adult hippocampal neurogenesis. Moreover, a dysfunction of vitamin A hippocampal signalling pathway has been involved in the appearance of age-related memory deficits but also in adult hippocampal neurogenesis alterations. The present study aims at testing the hypothesis that a mid-life vitamin A supplementation would be a successful strategy to prevent age-related memory deficits. Thus, middle-aged Wistar rats were submitted to a vitamin A enriched diet and were tested 4 months later in a spatial memory task. In order to better understand the potential mechanisms mediating the effects of vitamin A supplementation on hippocampal functions, we studied different aspects of hippocampal adult neurogenesis and evaluated hippocampal CRABP-I expression, known to modulate differentiation processes. Here, we show that vitamin A supplementation from middle-age enhances spatial memory and improves the dendritic arborisation of newborn immature neurons probably resulting in a better survival and neuronal differentiation in aged rats. Moreover, our results suggest that hippocampal CRABP-I expression which controls the intracellular availability of retinoic acid (RA), may be an important regulator of neuronal differentiation processes in the aged hippocampus. Thus, vitamin A supplementation from middle-age could be a good strategy to maintain hippocampal plasticity and functions. PMID:23977218

  19. A Mid-Life Vitamin A Supplementation Prevents Age-Related Spatial Memory Deficits and Hippocampal Neurogenesis Alterations through CRABP-I

    PubMed Central

    Touyarot, Katia; Bonhomme, Damien; Roux, Pascale; Alfos, Serge; Lafenêtre, Pauline; Richard, Emmanuel; Higueret, Paul; Pallet, Véronique

    2013-01-01

    Age-related memory decline including spatial reference memory is considered to begin at middle-age and coincides with reduced adult hippocampal neurogenesis. Moreover, a dysfunction of vitamin A hippocampal signalling pathway has been involved in the appearance of age-related memory deficits but also in adult hippocampal neurogenesis alterations. The present study aims at testing the hypothesis that a mid-life vitamin A supplementation would be a successful strategy to prevent age-related memory deficits. Thus, middle-aged Wistar rats were submitted to a vitamin A enriched diet and were tested 4 months later in a spatial memory task. In order to better understand the potential mechanisms mediating the effects of vitamin A supplementation on hippocampal functions, we studied different aspects of hippocampal adult neurogenesis and evaluated hippocampal CRABP-I expression, known to modulate differentiation processes. Here, we show that vitamin A supplementation from middle-age enhances spatial memory and improves the dendritic arborisation of newborn immature neurons probably resulting in a better survival and neuronal differentiation in aged rats. Moreover, our results suggest that hippocampal CRABP-I expression which controls the intracellular availability of retinoic acid (RA), may be an important regulator of neuronal differentiation processes in the aged hippocampus. Thus, vitamin A supplementation from middle-age could be a good strategy to maintain hippocampal plasticity and functions. PMID:23977218

  20. Effects of Long-Term Environmental Enrichment on Anxiety, Memory, Hippocampal Plasticity and Overall Brain Gene Expression in C57BL6 Mice

    PubMed Central

    Hüttenrauch, Melanie; Salinas, Gabriela; Wirths, Oliver

    2016-01-01

    There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging wild-type (WT) mice has not yet been studied in detail. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE) paradigm for a duration of 11 months, leads to reduced anxiety and improved spatial reference memory in C57BL6 WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH) and EE mice, the number of dentate gyrus (DG) neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders. PMID:27536216

  1. Effects of Long-Term Environmental Enrichment on Anxiety, Memory, Hippocampal Plasticity and Overall Brain Gene Expression in C57BL6 Mice.

    PubMed

    Hüttenrauch, Melanie; Salinas, Gabriela; Wirths, Oliver

    2016-01-01

    There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer's disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging wild-type (WT) mice has not yet been studied in detail. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE) paradigm for a duration of 11 months, leads to reduced anxiety and improved spatial reference memory in C57BL6 WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH) and EE mice, the number of dentate gyrus (DG) neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders. PMID:27536216

  2. Effects of Long-Term Environmental Enrichment on Anxiety, Memory, Hippocampal Plasticity and Overall Brain Gene Expression in C57BL6 Mice.

    PubMed

    Hüttenrauch, Melanie; Salinas, Gabriela; Wirths, Oliver

    2016-01-01

    There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer's disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging wild-type (WT) mice has not yet been studied in detail. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE) paradigm for a duration of 11 months, leads to reduced anxiety and improved spatial reference memory in C57BL6 WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH) and EE mice, the number of dentate gyrus (DG) neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders.

  3. Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo.

    PubMed

    Zhang, Cheng Gao; Kim, Sung-Jin

    2007-01-01

    Taurine has a variety of actions in the body such as cardiotonic, host-defensive, radioprotective and glucose-regulatory effects. However, its action in the central nervous system remains to be characterized. In the present study, we tested to see whether taurine exerts anti-anxiety effects and to explore its mechanism of anti-anxiety activity in vivo. The staircase test and elevated plus maze test were performed to test the anti-anxiety action of taurine. Convulsions induced by strychnine, picrotoxin, yohimbine and isoniazid were tested to explore the mechanism of anti-anxiety activity of taurine. The Rotarod test was performed to test muscle relaxant activity and the passive avoidance test was carried out to test memory activity in response to taurine. Taurine (200 mg/kg, p.o.) significantly reduced rearing numbers in the staircase test while it increased the time spent in the open arms as well as the number of entries to the open arms in the elevated plus maze test, suggesting that it has a significant anti-anxiety activity. Taurine's action could be due to its binding to and activating of strychnine-sensitive glycine receptor in vivo as it inhibited convulsion caused by strychnine; however, it has little effect on picrotoxin-induced convulsion, suggesting its anti-anxiety activity may not be linked to GABA receptor. It did not alter memory function and muscle activity. Taken together, these results suggest that taurine could be beneficial for the control of anxiety in the clinical situations.

  4. Phenotypic and functional alteration of CD4+ T cells after antigen stimulation. Resolution of two populations of memory T cells that both secrete interleukin 4

    PubMed Central

    1989-01-01

    Phenotypic and functional alteration of murine CD4+ T cells after antigenic stimulation was studied using two anti-T cell mAbs recently described that define four distinct T cell subsets. Activation of T cells resulted in the permanent loss of 3G11 expression. However, two phenotypically distinct memory T cell populations were established depending on the system used; whereas those for anti-KLH antibody response were enriched in the fraction expression 6C10 (Fr. III), memory T cells for the allogeneic MLR lacked such expression (Fr. IV). Furthermore, successive stimulation with antigen in vitro resulted in secretion of IL-4 without detectable IL-2. This alteration of phenotype and interleukin secretion was also demonstrable when starting with 3G11+6C10- cells (Fr. I), the fraction that secretes IL-2 exclusively upon activation. PMID:2525174

  5. tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study.

    PubMed

    Kim, Soyoung; Stephenson, Mary C; Morris, Peter G; Jackson, Stephen R

    2014-10-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task.

  6. Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.

    PubMed

    Simone, Jean; Bogue, Elizabeth A; Bhatti, Dionnet L; Day, Laura E; Farr, Nathan A; Grossman, Anna M; Holmes, Philip V

    2015-12-01

    In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory.

  7. Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine.

    PubMed

    Featherstone, Robert E; Burton, Christie L; Coppa-Hopman, Romina; Rizos, Zoë; Sinyard, Judy; Kapur, Shitij; Fletcher, Paul J

    2009-10-01

    Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose-response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.

  8. Prenatal methamphetamine exposure induces long-lasting alterations in memory and development of NMDA receptors in the hippocampus.

    PubMed

    Šlamberová, R; Vrajová, M; Schutová, B; Mertlová, M; Macúchová, E; Nohejlová, K; Hrubá, L; Puskarčíková, J; Bubeníková-Valešová, V; Yamamotová, A

    2014-01-01

    Since close relationship was shown between drug addiction and memory formation, the aim of the present study was to investigate the effects of interaction between prenatal methamphetamine (MA) exposure and MA treatment in adulthood on spatial and non-spatial memory and on the structure of the N-methyl-D-aspartate (NMDA) receptors in the hippocampus. Adult male rats prenatally exposed to MA (5 mg/kg) or saline were tested in adulthood. Non-spatial memory was examined in the Object Recognition Test (ORT) and spatial memory in the Object Location Test (OLT) and in the Memory Retention Test (MRT) conducted in the Morris Water Maze (MWM), respectively. Based on the type of the memory test animals were injected either acutely (ORT, OLT) or long-term (MWM) with MA (1 mg/kg). After each testing, animals were sacrificed and brains were removed. The hippocampus was then examined in Western Blot analysis for occurrence of different NMDA receptors' subtypes. Our results demonstrated that prenatal MA exposure affects the development of the NMDA receptors in the hippocampus that might correspond with improvement of spatial memory tested in adulthood in the MWM. On the other hand, the effect of prenatal MA exposure on non-spatial memory examined in the ORT was the opposite. In addition, we showed that the effect of MA administration in adulthood on NMDA receptors is influenced by prenatal MA exposure, which seems to correlate with the spatial memory examined in the OLT.

  9. Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior.

    PubMed

    Guha, Suman K; Tillu, Rucha; Sood, Ankit; Patgaonkar, Mandar; Nanavaty, Ishira N; Sengupta, Arjun; Sharma, Shobhona; Vaidya, Vidita A; Pathak, Sulabha

    2014-11-01

    Cerebral malaria is associated with cerebrovascular damage and neurological sequelae. However, the neurological consequences of uncomplicated malaria, the most prevalent form of the disease, remain uninvestigated. Here, using a mild malaria model, we show that a single Plasmodium chabaudi adami infection in adult mice induces neuroinflammation, neurogenic, and behavioral changes in the absence of a blood-brain barrier breach. Using cytokine arrays we show that the infection induces differential serum and brain cytokine profiles, both at peak parasitemia and 15days post-parasite clearance. At the peak of infection, along with the serum, the brain also exhibited a definitive pro-inflammatory cytokine profile, and gene expression analysis revealed that pro-inflammatory cytokines were also produced locally in the hippocampus, an adult neurogenic niche. Hippocampal microglia numbers were enhanced, and we noted a shift to an activated profile at this time point, accompanied by a striking redistribution of the microglia to the subgranular zone adjacent to hippocampal neuronal progenitors. In the hippocampus, a distinct decline in progenitor turnover and survival was observed at peak parasitemia, accompanied by a shift from neuronal to glial fate specification. Studies in transgenic Nestin-GFP reporter mice demonstrated a decline in the Nestin-GFP(+)/GFAP(+) quiescent neural stem cell pool at peak parasitemia. Although these cellular changes reverted to normal 15days post-parasite clearance, specific brain cytokines continued to exhibit dysregulation. Behavioral analysis revealed selective deficits in social and anxiety-like behaviors, with no change observed in locomotor, cognitive, and depression-like behaviors, with a return to baseline at recovery. Collectively, these findings indicate that even a single episode of mild malaria results in alterations of the brain cytokine profile, causes specific behavioral dysfunction, is accompanied by hippocampal microglial

  10. Hippocampal Injections of Oligomeric Amyloid β-peptide (1–42) Induce Selective Working Memory Deficits and Long-lasting Alterations of ERK Signaling Pathway

    PubMed Central

    Faucher, Pierre; Mons, Nicole; Micheau, Jacques; Louis, Caroline; Beracochea, Daniel J.

    2016-01-01

    Increasing evidence suggests that abnormal brain accumulation of soluble rather than aggregated amyloid-β1–42 oligomers (Aβo(1–42)) plays a causal role in Alzheimer’s disease (AD). However, as yet, animal’s models of AD based on oligomeric amyloid-β1–42 injections in the brain have not investigated their long-lasting impacts on molecular and cognitive functions. In addition, the injections have been most often performed in ventricles, but not in the hippocampus, in spite of the fact that the hippocampus is importantly involved in memory processes and is strongly and precociously affected during the early stages of AD. Thus, in the present study, we investigated the long-lasting impacts of intra-hippocampal injections of oligomeric forms of Aβo(1–42) on working and spatial memory and on the related activation of ERK1/2. Indeed, the extracellular signal-regulated kinase (ERK) which is involved in memory function had been found to be activated by amyloid peptides. We found that repeated bilateral injections (1injection/day over 4 successive days) of oligomeric forms of Aβo(1–42) into the dorsal hippocampus lead to long-lasting impairments in two working memory tasks, these deficits being observed 7 days after the last injection, while spatial memory remained unaffected. Moreover, the working memory deficits were correlated with sustained impairments of ERK1/2 activation in the medial prefrontal cortex (mPFC) and the septum, two brain areas tightly connected with the hippocampus and involved in working memory. Thus, our study is first to evidence that sub-chronic injections of oligomeric forms of Aβo(1–42) into the dorsal hippocampus produces the main sign of cognitive impairments corresponding to the early stages of AD, via long-lasting alterations of an ERK/MAPK pathway in an interconnected brain networks. PMID:26793098

  11. Hippocampal Injections of Oligomeric Amyloid β-peptide (1-42) Induce Selective Working Memory Deficits and Long-lasting Alterations of ERK Signaling Pathway.

    PubMed

    Faucher, Pierre; Mons, Nicole; Micheau, Jacques; Louis, Caroline; Beracochea, Daniel J

    2015-01-01

    Increasing evidence suggests that abnormal brain accumulation of soluble rather than aggregated amyloid-β1-42 oligomers (Aβo(1-42)) plays a causal role in Alzheimer's disease (AD). However, as yet, animal's models of AD based on oligomeric amyloid-β1-42 injections in the brain have not investigated their long-lasting impacts on molecular and cognitive functions. In addition, the injections have been most often performed in ventricles, but not in the hippocampus, in spite of the fact that the hippocampus is importantly involved in memory processes and is strongly and precociously affected during the early stages of AD. Thus, in the present study, we investigated the long-lasting impacts of intra-hippocampal injections of oligomeric forms of Aβo(1-42) on working and spatial memory and on the related activation of ERK1/2. Indeed, the extracellular signal-regulated kinase (ERK) which is involved in memory function had been found to be activated by amyloid peptides. We found that repeated bilateral injections (1injection/day over 4 successive days) of oligomeric forms of Aβo(1-42) into the dorsal hippocampus lead to long-lasting impairments in two working memory tasks, these deficits being observed 7 days after the last injection, while spatial memory remained unaffected. Moreover, the working memory deficits were correlated with sustained impairments of ERK1/2 activation in the medial prefrontal cortex (mPFC) and the septum, two brain areas tightly connected with the hippocampus and involved in working memory. Thus, our study is first to evidence that sub-chronic injections of oligomeric forms of Aβo(1-42) into the dorsal hippocampus produces the main sign of cognitive impairments corresponding to the early stages of AD, via long-lasting alterations of an ERK/MAPK pathway in an interconnected brain networks. PMID:26793098

  12. Involvement of GABAB receptors in biochemical alterations induced by anxiety-related responses to nicotine in mice: genetic and pharmacological approaches.

    PubMed

    Varani, Andrés P; Pedrón, Valeria T; Bettler, Bernhard; Balerio, Graciela N

    2014-06-01

    Previous studies from our laboratory showed that anxiety-related responses induced by nicotine (NIC), measured by the elevated plus maze, were abolished by 2-OH-saclofen (GABAB receptor antagonist) (1 mg/kg; ip) or the lack of GABAB receptors (GABAB1 knockout mice). Based on these behavioral data, the aims of the present study were: 1) to evaluate the possible neurochemical changes (dopamine, DA, serotonin, 5-HT, 3,4-dihydroxyphenylacetic acid, DOPAC, 5-hydroxyindoleacetic acid, 5-HIAA and noradrenaline, NA) and the c-Fos expression induced by the anxiolytic (0.05 mg/kg) or anxiogenic (0.8 mg/kg) doses of NIC in the dorsal raphe (DRN) and lateral septal (LSN) nucleus; 2) to study the possible involvement of GABAB receptors on the neurochemical alterations and c-Fos expression induced by NIC (0.05 and 0.8 mg/kg), using both pharmacological (2-OH-saclofen) and genetic (mice GABAB1 knockout) approaches. The results revealed that in wild-type mice, NIC (0.05 mg/kg) increased the concentration of 5-HT and 5-HIAA (p < 0.05) in the DRN, and NIC (0.8 mg/kg) increased the levels of 5-HT (p < 0.01) and NA (p < 0.05) in the LSN. Additionally, 2-OH-saclofen pretreatment (1 mg/kg, ip) or the lack of GABAB receptors abolished these neurochemical changes induced by NIC (p < 0.01, p < 0.05, respectively). On the other hand, NIC 0.05 and 0.8 mg/kg increased (p < 0.01) the c-Fos expression in the DRN and LSN respectively, in wild-type mice. In addition, 2-OH-saclofen pretreatment (1 mg/kg, ip) or the lack of GABAB receptors prevented the c-Fos alterations induced by NIC (p < 0.01). In summary, both approaches show that GABAB receptors would participate in the modulation of anxiolytic- and anxiogenic-like responses induced by NIC, suggesting the potential therapeutic target of these receptors for the tobacco addiction treatment.

  13. Deletion of the GluA1 AMPA Receptor Subunit Alters the Expression of Short-Term Memory

    ERIC Educational Resources Information Center

    Sanderson, David J.; Sprengel, Rolf; Seeburg, Peter H.; Bannerman, David M.

    2011-01-01

    Deletion of the GluA1 AMPA receptor subunit selectively impairs short-term memory for spatial locations. We further investigated this deficit by examining memory for discrete nonspatial visual stimuli in an operant chamber. Unconditioned suppression of magazine responding to visual stimuli was measured in wild-type and GluA1 knockout mice.…

  14. The impact of anxiety upon cognition: perspectives from human threat of shock studies

    PubMed Central

    Robinson, Oliver J.; Vytal, Katherine; Cornwell, Brian R.; Grillon, Christian

    2013-01-01

    Anxiety disorders constitute a sizeable worldwide health burden with profound social and economic consequences. The symptoms are wide-ranging; from hyperarousal to difficulties with concentrating. This latter effect falls under the broad category of altered cognitive performance which is the focus of this review. Specifically, we examine the interaction between anxiety and cognition focusing on the translational threat of unpredictable shock paradigm; a method previously used to characterize emotional responses and defensive mechanisms that is now emerging as valuable tool for examining the interaction between anxiety and cognition. In particular, we compare the impact of threat of shock on cognition in humans to that of pathological anxiety disorders. We highlight that both threat of shock and anxiety disorders promote mechanisms associated with harm avoidance across multiple levels of cognition (from perception to attention to learning and executive function)—a “hot” cognitive function which can be both adaptive and maladaptive depending upon the circumstances. This mechanism comes at a cost to other functions such as working memory, but leaves some functions, such as planning, unperturbed. We also highlight a number of cognitive effects that differ across anxiety disorders and threat of shock. These discrepant effects are largely seen in “cold” cognitive functions involving control mechanisms and may reveal boundaries between adaptive (e.g., response to threat) and maladaptive (e.g., pathological) anxiety. We conclude by raising a number of unresolved questions regarding the role of anxiety in cognition that may provide fruitful avenues for future research. PMID:23730279

  15. Anxiety phenotype in mice that overexpress protein kinase A.

    PubMed

    Keil, Margaret F; Briassoulis, George; Gokarn, Nirmal; Nesterova, Maria; Wu, T John; Stratakis, Constantine A

    2012-06-01

    The role of cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling in the molecular pathways involved in fear and memory is well established. Prior studies in our lab reported that transgenic mice with an inactivating mutation in Prkar1a gene (codes for the 1-alpha regulatory subunit (R1α) of PKA) exhibited behavioral abnormalities including anxiety and depression. In the present study, we examined the role of altered PKA signaling on anxiety-like behaviors in Prkar1a(+/-) mice compared to wild-type (WT) littermates. The elevated plus maze (EPM) and marble bury (MB) tests were used to assess anxiety-like behavior. The hotplate test was performed to evaluate analgesia. We further examined the impact of the Prkar1a inactivating mutation on PKA activity in specific nuclei of the brain associated with anxiety-like behavior. Results for the MB test showed a genotype effect, with increased anxiety-like behavior in Prkar1a(+/-) mice, compared to WT littermates (p<0.05). MANOVA analysis showed a significant genotype difference in anxiety-like behavior in the EPM between WT and Prkar1a(+/-) mice on combined dependent variables (open arm time and open to total time ratio; p<0.05). Results of hotplate testing showed no genotype effect however; the expected sex difference was noted. Analysis of PKA activity showed the loss of one Prkar1a allele led to an increase in basal and cAMP-stimulated kinase activity in both the basolateral and central amygdala. These results suggest that the alteration in PKA signaling in Prkar1a(+/-) mice is not a ubiquitous effect; and supports the importance of cAMP/PKA pathway in neurobiological processes involved in anxiety and fear sensitization. PMID:22024111

  16. Anxiety phenotype in mice that overexpress protein kinase A.

    PubMed

    Keil, Margaret F; Briassoulis, George; Gokarn, Nirmal; Nesterova, Maria; Wu, T John; Stratakis, Constantine A

    2012-06-01

    The role of cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling in the molecular pathways involved in fear and memory is well established. Prior studies in our lab reported that transgenic mice with an inactivating mutation in Prkar1a gene (codes for the 1-alpha regulatory subunit (R1α) of PKA) exhibited behavioral abnormalities including anxiety and depression. In the present study, we examined the role of altered PKA signaling on anxiety-like behaviors in Prkar1a(+/-) mice compared to wild-type (WT) littermates. The elevated plus maze (EPM) and marble bury (MB) tests were used to assess anxiety-like behavior. The hotplate test was performed to evaluate analgesia. We further examined the impact of the Prkar1a inactivating mutation on PKA activity in specific nuclei of the brain associated with anxiety-like behavior. Results for the MB test showed a genotype effect, with increased anxiety-like behavior in Prkar1a(+/-) mice, compared to WT littermates (p<0.05). MANOVA analysis showed a significant genotype difference in anxiety-like behavior in the EPM between WT and Prkar1a(+/-) mice on combined dependent variables (open arm time and open to total time ratio; p<0.05). Results of hotplate testing showed no genotype effect however; the expected sex difference was noted. Analysis of PKA activity showed the loss of one Prkar1a allele led to an increase in basal and cAMP-stimulated kinase activity in both the basolateral and central amygdala. These results suggest that the alteration in PKA signaling in Prkar1a(+/-) mice is not a ubiquitous effect; and supports the importance of cAMP/PKA pathway in neurobiological processes involved in anxiety and fear sensitization.

  17. Alterations of 5-HT1A receptor-induced G-protein functional activation and relationship to memory deficits in patients with pharmacoresistant temporal lobe epilepsy.

    PubMed

    Cuellar-Herrera, Manola; Velasco, Ana Luisa; Velasco, Francisco; Trejo, David; Alonso-Vanegas, Mario; Nuche-Bricaire, Avril; Vázquez-Barrón, Daruni; Guevara-Guzmán, Rosalinda; Rocha, Luisa

    2014-12-01

    The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron emission tomography (PET) studies in patients with mesial temporal lobe epilepsy (mTLE) have demonstrated that a decrease in 5-HT1A receptor binding in temporal regions may play a role in memory impairment. The evidences lead us to speculate whether this decrease in receptor binding is associated with a reduced receptor number or if the functionality of the 5-HT1A receptor-induced G-protein activation and/or the second messenger cascade is modified. The purpose of the present study is to determine 5-HT1A receptor-induced G-protein functional activation by 8-OH-DPAT-stimulated [(35)S]GTPγS binding assay in hippocampal tissue of surgical patients with mTLE. We correlate functional activity with epilepsy history and neuropsychological assessment of memory. We found that maximum functional activation stimulation values (Emax) of [(35)S]GTPγS binding were significantly increased in mTLE group when compared to autopsy samples. Furthermore, significant correlations were found: (1) positive coefficients between the Emax with the age of patient and frequency of seizures; (2) negative coefficients between the Emax and working memory, immediate recall and delayed recall memory tasks. Our data suggest that the epileptic hippocampus of patients with mTLE presents an increase in 5-HT1A receptor-induced G-protein functional activation, and that this altered activity is related to age and seizure frequency, as well as to memory consolidation deficit.

  18. Alterations of 5-HT1A receptor-induced G-protein functional activation and relationship to memory deficits in patients with pharmacoresistant temporal lobe epilepsy.

    PubMed

    Cuellar-Herrera, Manola; Velasco, Ana Luisa; Velasco, Francisco; Trejo, David; Alonso-Vanegas, Mario; Nuche-Bricaire, Avril; Vázquez-Barrón, Daruni; Guevara-Guzmán, Rosalinda; Rocha, Luisa

    2014-12-01

    The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron emission tomography (PET) studies in patients with mesial temporal lobe epilepsy (mTLE) have demonstrated that a decrease in 5-HT1A receptor binding in temporal regions may play a role in memory impairment. The evidences lead us to speculate whether this decrease in receptor binding is associated with a reduced receptor number or if the functionality of the 5-HT1A receptor-induced G-protein activation and/or the second messenger cascade is modified. The purpose of the present study is to determine 5-HT1A receptor-induced G-protein functional activation by 8-OH-DPAT-stimulated [(35)S]GTPγS binding assay in hippocampal tissue of surgical patients with mTLE. We correlate functional activity with epilepsy history and neuropsychological assessment of memory. We found that maximum functional activation stimulation values (Emax) of [(35)S]GTPγS binding were significantly increased in mTLE group when compared to autopsy samples. Furthermore, significant correlations were found: (1) positive coefficients between the Emax with the age of patient and frequency of seizures; (2) negative coefficients between the Emax and working memory, immediate recall and delayed recall memory tasks. Our data suggest that the epileptic hippocampus of patients with mTLE presents an increase in 5-HT1A receptor-induced G-protein functional activation, and that this altered activity is related to age and seizure frequency, as well as to memory consolidation deficit. PMID:25304920

  19. Learning and memory alterations are associated with hippocampal N-acetylaspartate in a rat model of depression as measured by 1H-MRS.

    PubMed

    Xi, Guangjun; Hui, Jiaojie; Zhang, Zhijun; Liu, Shanshan; Zhang, Xiangrong; Teng, Gaojun; Chan, Kevin C; Wu, Ed X; Nie, Binbin; Shan, Baoci; Li, Lingjiang; Reynolds, Gavin P

    2011-01-01

    It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

  20. Social exclusion intensifies anxiety-like behavior in adolescent rats.

    PubMed

    Lee, Hyunchan; Noh, Jihyun

    2015-05-01

    Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration.

  1. Action video game playing is associated with improved visual sensitivity, but not alterations in visual sensory memory.

    PubMed

    Appelbaum, L Gregory; Cain, Matthew S; Darling, Elise F; Mitroff, Stephen R

    2013-08-01

    Action video game playing has been experimentally linked to a number of perceptual and cognitive improvements. These benefits are captured through a wide range of psychometric tasks and have led to the proposition that action video game experience may promote the ability to extract statistical evidence from sensory stimuli. Such an advantage could arise from a number of possible mechanisms: improvements in visual sensitivity, enhancements in the capacity or duration for which information is retained in visual memory, or higher-level strategic use of information for decision making. The present study measured the capacity and time course of visual sensory memory using a partial report performance task as a means to distinguish between these three possible mechanisms. Sensitivity measures and parameter estimates that describe sensory memory capacity and the rate of memory decay were compared between individuals who reported high evels and low levels of action video game experience. Our results revealed a uniform increase in partial report accuracy at all stimulus-to-cue delays for action video game players but no difference in the rate or time course of the memory decay. The present findings suggest that action video game playing may be related to enhancements in the initial sensitivity to visual stimuli, but not to a greater retention of information in iconic memory buffers. PMID:23709062

  2. Action video game playing is associated with improved visual sensitivity, but not alterations in visual sensory memory.

    PubMed

    Appelbaum, L Gregory; Cain, Matthew S; Darling, Elise F; Mitroff, Stephen R

    2013-08-01

    Action video game playing has been experimentally linked to a number of perceptual and cognitive improvements. These benefits are captured through a wide range of psychometric tasks and have led to the proposition that action video game experience may promote the ability to extract statistical evidence from sensory stimuli. Such an advantage could arise from a number of possible mechanisms: improvements in visual sensitivity, enhancements in the capacity or duration for which information is retained in visual memory, or higher-level strategic use of information for decision making. The present study measured the capacity and time course of visual sensory memory using a partial report performance task as a means to distinguish between these three possible mechanisms. Sensitivity measures and parameter estimates that describe sensory memory capacity and the rate of memory decay were compared between individuals who reported high evels and low levels of action video game experience. Our results revealed a uniform increase in partial report accuracy at all stimulus-to-cue delays for action video game players but no difference in the rate or time course of the memory decay. The present findings suggest that action video game playing may be related to enhancements in the initial sensitivity to visual stimuli, but not to a greater retention of information in iconic memory buffers.

  3. Math Performance as a Function of Math Anxiety and Arousal Performance Theory

    ERIC Educational Resources Information Center

    Farnsworth, Donald M., Jr.

    2009-01-01

    While research continues to link increased math anxiety with reduced working memory, the exact nature of the relationship remains elusive. In addition, research regarding the extent of the impact math anxiety has on working memory is contradictory. This research clarifies the directional nature of math anxiety as it pertains to working memory, and…

  4. Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats - An animal model of autism.

    PubMed

    Olexová, Lucia; Štefánik, Peter; Kršková, Lucia

    2016-08-26

    Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test. The levels of the 65 and 67kDa enzymes of l-glutamic acid decarboxylase (GAD) mRNAs and type 1 GABA transporter (GAT1) were evaluated in the amygdala, as well as GABA producing enzymes in the cortex layer of the cerebellum. Our research showed that adult VPA rats spent less time in the inner zone of the testing chamber and more time in the outer zone of the testing chamber in the open field test. We also found that adult VPA rats had increased expression of GAT1 in the amygdala, as well as decreased levels of GAD65 and GAD67 mRNA in the cerebellum compared to control animals. These findings support the existence of a relationship between increased anxiety-like behaviour and changes in the regulation of the GABAergic system in VPA rats.

  5. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system.

    PubMed

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-06-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

  6. Testosterone, but not nonaromatizable dihydrotestosterone, improves working memory and alters nerve growth factor levels in aged male rats.

    PubMed

    Bimonte-Nelson, Heather A; Singleton, Rachel S; Nelson, Matthew E; Eckman, Christopher B; Barber, John; Scott, Tonetta Y; Granholm, Ann-Charlotte E

    2003-06-01

    Recent studies have suggested that testosterone levels are lower in men with Alzheimer's disease and that testosterone treatment improves cognition in older men. Since testosterone can be aromatized to estrogen, testosterone's effects could be due to conversion into estrogen. We treated aged male rats with either testosterone or dihydrotestosterone (DHT), the latter of which is not aromatized to estrogen, in order to determine whether these treatments improve spatial working and reference memory as assessed in the water radial arm maze. We also tested whether such effects are related to beta-amyloid levels in the hippocampus or neurotrophin levels in the hippocampus, entorhinal cortex, frontal cortex, or striatum. Aged rats made more errors than young rats on all memory measures. Testosterone, but not DHT, improved working memory and decreased hippocampal NGF protein in aged rats, while having no effect on beta-amyloid. However, higher beta-amyloid levels were correlated with poorer working memory performance in young rats. Neurotrophin levels in entorhinal cortex were positively correlated with errors for all memory measures in androgen-treated rats. Similar to findings in human studies, in our study androgen treatment lowered circulating estradiol levels in aged rats, suggesting that androgen treatment exerts feedback to the hypothalamic pituitary axis and that conversion to estrogen may not be the underlying biological mechanism of testosterone's effects on memory and growth factor levels. The ratio of estradiol to testosterone, or the actions of the aromatase enzyme itself, may be responsible for the observed effects. These data support the hypothesis that testosterone therapy in aging men may provide positive effects on cognition and that neural regions that are linked to cognition, such as the hippocampus and/or entorhinal cortex, may be involved in such effects.

  7. Test Anxiety

    MedlinePlus

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q& ... Like other anxiety reactions, test anxiety affects the body and the mind. When you're under stress, your body releases ...

  8. Environmental enrichment for adult rats: effects on trait and state anxiety.

    PubMed

    Goes, Tiago Costa; Antunes, Fabrício Dias; Teixeira-Silva, Flavia

    2015-01-01

    Experimental evidence indicates that enriched environment (EE) induces neurobiological and behavioural alterations. EE in early life improves learning and memory and reduces trait and state anxiety. However, the effect of EE established in adulthood has rarely been investigated. Thus, the aim of this study was to evaluate the possibility of modifying the levels of trait and/or state anxiety of adult rats exposed to EE. Seventy adult Wistar male rats were first tested in the free-exploratory paradigm (FEP) and were categorized according to their levels of trait anxiety (high, medium and low). Subsequently, half of the animals from each category returned to their home cages (standard condition: SC) and the other half was transferred to an enriched environment (enriched condition: EC). After three weeks, all animals were again tested in FEP. Seven to 10 days later, fifty of the seventy animals were tested on the elevated plus-maze test (EPM). In FEP, EE reduced locomotor activity in the second exposition independently of the anxiety category and, it decreased the levels of trait anxiety of highly anxious rats. No effect of EE was observed on EPM. In conclusion, EE established in adulthood was able to reduce high trait anxiety, a major risk factor for anxiety disorders.

  9. Anxiety Disorders

    ERIC Educational Resources Information Center

    Klein, Rachel G.

    2009-01-01

    Because of their high prevalence and their negative long-term consequences, child anxiety disorders have become an important focus of interest. Whether pathological anxiety and normal fear are similar processes continues to be controversial. Comparative studies of child anxiety disorders are scarce, but there is some support for the current…

  10. Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat

    PubMed Central

    Motaghinejad, Majid; Motevalian, Manijeh; Larijani, Setare Farokhi; Khajehamedi, Zohreh

    2015-01-01

    Background: Methylphenidate (MPH), a neural stimulant, can cause damages to brain; the chronic neurochemical and behavioral effects of MPH remain unclear. Exercise lowers stress and anxiety and can act as non-pharmacologic neuroprotective agent. In this study protective effects of exercise in MPH-induced anxiety, depression and cognition impairment were investigated. Materials and Methods: Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control, received normal saline (0.2 ml/rat) for 21 days, group 2 and 3 (as positive controls) received MPH (10 and 20 mg/kg) for 21 days. Groups 4 and 5 concurrently were treated with MPH (10 and 20 mg/kg) and forced exercise for 21 days. On day 21, Elevated Plus Maze (EPM), Open Field Test (OFT), Forced Swim Test (FST) and Tail Suspension Test (TST) were used to investigate the level of anxiety and depression in animals. In addition between 17th and 21th days, Morris Water Maze (MWM) was applied to evaluate the effect of MPH on spatial learning and memory. Results: MPH-treated animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM and TST which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. Forced exercise by treadmill can attenuate MPH-induced anxiety, depression and motor activity alteration in OFT. MPH also can disturb learning and memory in MWM and forced exercise can neutralize this effect of MPH. Conclusion: We conclude that forced exercise can be protective in brain against MPH-induced anxiety, depression and cognition alteration. PMID:26322282

  11. Repeated stimulation of dopamine D1-like receptor and hyperactivation of mTOR signaling lead to generalized seizures, altered dentate gyrus plasticity, and memory deficits.

    PubMed

    Gangarossa, Giuseppe; Ceolin, Laura; Paucard, Alexia; Lerner-Natoli, Mireille; Perroy, Julie; Fagni, Laurent; Valjent, Emmanuel

    2014-12-01

    The acute activation of the dopamine D1-like receptors (D1R) is involved in a plethora of functions ranging from increased locomotor activity to the facilitation of consolidation, storage, and retrieval of memories. Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic transmission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of repeated stimulation of D1R using the selective D1R-like agonist SKF81297. Here, we report that repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that repeated stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR signaling, disrupted hippocampal plasticity, and impaired long-term recognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits.

  12. Drebrin depletion alters neurotransmitter receptor levels in protein complexes, dendritic spine morphogenesis and memory-related synaptic plasticity in the mouse hippocampus.

    PubMed

    Jung, Gangsoo; Kim, Eun-Jung; Cicvaric, Ana; Sase, Sunetra; Gröger, Marion; Höger, Harald; Sialana, Fernando Jayson; Berger, Johannes; Monje, Francisco J; Lubec, Gert

    2015-07-01

    Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild-type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine receptor 1A (5-HT1(A)R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel-based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory-related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory-related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.

  13. Altered likelihood of brain activation in attention and working memory networks in patients with multiple sclerosis: An ALE meta-analysis☆

    PubMed Central

    Kollndorfer, K.; Krajnik, J.; Woitek, R.; Freiherr, J.; Prayer, D.; Schöpf, V.

    2013-01-01

    Multiple sclerosis (MS) is a chronic neurological disease, frequently affecting attention and working memory functions. Functional imaging studies investigating those functions in MS patients are hard to compare, as they include heterogeneous patient groups and use different paradigms for cognitive testing. The aim of this study was to investigate alterations in neuronal activation between MS patients and healthy controls performing attention and working memory tasks. Two meta-analyses of previously published fMRI studies investigating attention and working memory were conducted for MS patients and healthy controls, respectively. Resulting maps were contrasted to compare brain activation in patients and healthy controls. Significantly increased brain activation in the inferior parietal lobule and the dorsolateral prefrontal cortex was detected for healthy controls. In contrast, higher neuronal activation in MS patients was obtained in the left ventrolateral prefrontal cortex and the right premotor area. With this meta-analytic approach previous results of investigations examining cognitive function using fMRI are summarized and compared. Therefore a more general view on cognitive dysfunction in this heterogeneous disease is enabled. PMID:24056084

  14. The recovery of acetylcholinesterase activity and the progression of neuropathological and pathophysiological alterations in the rat basolateral amygdala after soman-induced status epilepticus: relation to anxiety-like behavior.

    PubMed

    Prager, Eric M; Aroniadou-Anderjaska, Vassiliki; Almeida-Suhett, Camila P; Figueiredo, Taiza H; Apland, James P; Rossetti, Franco; Olsen, Cara H; Braga, Maria F M

    2014-06-01

    Organophosphorus nerve agents are powerful neurotoxins that irreversibly inhibit acetylcholinesterase (AChE) activity. One of the consequences of AChE inhibition is the generation of seizures and status epilepticus (SE), which cause brain damage, resulting in long-term neurological and behavioral deficits. Increased anxiety is the most common behavioral abnormality after nerve agent exposure. This is not surprising considering that the amygdala, and the basolateral nucleus of the amygdala (BLA) in particular, plays a central role in anxiety, and this structure suffers severe damage by nerve agent-induced seizures. In the present study, we exposed male rats to the nerve agent soman, at a dose that induce SE, and determined the time course of recovery of AChE activity, along with the progression of neuropathological and pathophysiological alterations in the BLA, during a 30-day period after exposure. Measurements were taken at 24 h, 7 days, 14 days, and 30 days after exposure, and at 14 and 30 days, anxiety-like behavior was also evaluated. We found that more than 90% of AChE is inhibited at the onset of SE, and AChE inhibition remains at this level 24 h later, in the BLA, as well as in the hippocampus, piriform cortex, and prelimbic cortex, which we analyzed for comparison. AChE activity recovered by day 7 in the BLA and day 14 in the other three regions. Significant neuronal loss and neurodegeneration were present in the BLA at 24 h and throughout the 30-day period. There was no significant loss of GABAergic interneurons in the BLA at 24 h post-exposure. However, by day 7, the number of GABAergic interneurons in the BLA was reduced, and at 14 and 30 days after soman, the ratio of GABAergic interneurons to the total number of neurons was lower compared to controls. Anxiety-like behavior in the open-field and the acoustic startle response tests was increased at 14 and 30 days post-exposure. Accompanying pathophysiological alterations in the BLA - studied in in

  15. The recovery of acetylcholinesterase activity and the progression of neuropathological and pathophysiological alterations in the rat basolateral amygdala after soman-induced status epilepticus: relation to anxiety-like behavior

    PubMed Central

    Prager, Eric M.; Aroniadou-Anderjaska, Vassiliki; Almeida-Suhett, Camila P.; Figueiredo, Taiza H.; Apland, James P.; Rossetti, Franco; Olsen, Cara H.; Braga, Maria F.M.

    2014-01-01

    Organophosphorus nerve agents are powerful neurotoxins that irreversibly inhibit acetylcholinesterase (AChE) activity. One of the consequences of AChE inhibition is the generation of seizures and status epilepticus (SE), which cause brain damage, resulting in long-term neurological and behavioral deficits. Increased anxiety is the most common behavioral abnormality after nerve agent exposure. This is not surprising considering that the amygdala, and the basolateral nucleus of the amygdala (BLA) in particular, plays a central role in anxiety, and this structure suffers severe damage by nerve agent-induced seizures. In the present study, we exposed male rats to lethal doses of the nerve agent soman, and determined the time course of recovery of AChE activity, along with the progression of neuropathological and pathophysiological alterations in the BLA, during a 30-day period after exposure. Measurements were taken at 24 hours, 7 days, 14 days, and 30 days after exposure, and at 14 and 30 days, anxiety-like behavior was also evaluated. We found that more than 90% of AChE is inhibited at the onset of SE, and AChE inhibition remains at this level 24 hours later, in the BLA, as well as in the hippocampus, piriform cortex, and prelimbic cortex, which we analyzed for comparison. AChE activity recovered by day 7 in the BLA and day 14 in the other three regions. Significant neuronal loss and neurodegeneration were present in the BLA at 24 hours and throughout the 30-day period. There was no significant loss of GABAergic interneurons in the BLA at 24 hours post-exposure. However, by day 7, the number of GABAergic interneurons in the BLA was reduced, and at 14 and 30 days after soman, the ratio of GABAergic interneurons to the total number of neurons was lower compared to controls. Anxiety-like behavior in the open-field and the acoustic startle response tests was increased at 14 and 30 days post-exposure. Accompanying pathophysiological alterations in the BLA – studied in

  16. Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice.

    PubMed

    Lyons, Angela M; Thiele, Todd E

    2010-12-01

    Neuropeptide Y (NPY) is a 36-amino-acid neuromodulator that is distributed throughout the central nervous system and has been implicated in a wide range of neurobiological responses including the integration of emotional behavior. The anxiolytic properties of NPY are modulated by NPY signaling in the hippocampus and in the central (CeA) and basolateral (BLA) nuclei of the amygdala. Recently, the neurotoxin saporin, when conjugated to NPY (NPY-SAP), was shown to selectively kill NPY receptor-expressing neurons and has been used as a tool to study the central NPY neurocircuitry involved with feeding behaviors. Here we determined if NPY-SAP can be used as a tool to study the central NPY neurocircuitry that modulates anxiety-like behaviors. BALB/cJ mice were given injection of either NPY-SAP or a control blank saporin (B-SAP) into the CeA or the basomedial hypothalamus (BMH) as a control injection site. The elevated zero maze test was used to assess anxiety-like behavior and NPY-SAP-induced lesions were verified using NPY Y1 receptor (Y1R) immunoreactivity (IR). Results showed that injection of NPY-SAP into the CeA site-specifically blunted Y1R IR in the CeA which was associated with a significant increase in anxiety-like behavior. Injection of NPY-SAP into the BMH, while locally blunting Y1R IR, promoted a compensatory increase of Y1R IR in the BLA and the CA3 region of the hippocampus which was associated with a significant reduction of anxiety-like behavior. The present set of experiments suggest that the NPY-SAP neurotoxin may be a useful tool for studying the NPY neurocircuitry that modulates anxiety-like behaviors.

  17. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP

    PubMed Central

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A.; Sumikawa, Katumi

    2014-01-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-d-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity. PMID:25545599

  18. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment

    PubMed Central

    Ramos-Chávez, Lucio A.; Rendón-López, Christian R. R.; Zepeda, Angélica; Silva-Adaya, Daniela; Del Razo, Luz M.; Gonsebatt, María E.

    2015-01-01

    Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH), which is the main antioxidant in the central nervous system (CNS). In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs) 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR) subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females. PMID:25709567

  19. Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring

    PubMed Central

    Wilson, Christina A.; Terry, Alvin V.

    2013-01-01

    Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the α7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

  20. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

    PubMed

    Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

    2015-01-01

    Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy

  1. Aberrant functional connectivity of resting state networks associated with trait anxiety.

    PubMed

    Modi, Shilpi; Kumar, Mukesh; Kumar, Pawan; Khushu, Subash

    2015-10-30

    Trait anxiety, a personality dimension, has been characterized by functional consequences such as increased distractibility, attentional bias in favor of threat-related information and hyper-responsive amygdala. However, literature on the association between resting state brain functional connectivity, as studied using resting state functional magnetic resonance imaging (rs-fMRI), and reported anxiety levels in the sub-clinical population is limited. In the present study, we employed rs-fMRI to investigate the possible alterations in the functional integrity of Resting State Networks (RSNs) associated with trait anxiety of the healthy subjects (15 high anxious and 14 low anxious). The rs-fMRI data was analyzed using independent component analysis and a dual regression approach that was applied on 12 RSNs that were identified using FSL. High anxious subjects showed significantly reduced functional connectivity in regions of the default mode network (posterior cingulate gyrus, middle and superior temporal gyrus, planum polare, supramarginal gyrus, temporal pole, angular gyrus and lateral occipital gyrus) which has been suggested to be involved in episodic memory, theory of mind, self-evaluation, and introspection, and perceptual systems including medial visual network, auditory network and another network involving temporal, parieto-occipital and frontal regions. Reduction in resting state connectivity in regions of the perceptual networks might underlie the perceptual, attentional and working memory deficits associated with trait anxiety. To our knowledge, this is the first study to relate trait anxiety to resting state connectivity using independent component analysis. PMID:26385540

  2. Alterations in the functional connectivity of a verbal working memory-related brain network in patients with left temporal lobe epilepsy.

    PubMed

    Huang, Wenli; Huang, Donghong; Chen, Zirong; Ye, Wei; Lv, Zongxia; Diao, Limei; Zheng, Jinou

    2015-08-18

    The aim of this study was to investigate the alterations in a verbal working memory (VWM)-related network in left temporal lobe epilepsy (lTLE) at rest. We evaluated 14 patients with lTLE and 14 control subjects by resting-state functional connectivity (RSFC). The region of interest was defined by the voxel with the highest Z-score during a VWM task according to functional magnetic resonance imaging in 16 healthy volunteers. Our study revealed that the network of RSFC was similar to the task-induced network in the healthy volunteers. Moreover, the patients with lTLE exhibited significantly decreased RSFC in the bilateral middle frontal gyrus, the inferior frontal gyrus and the inferior parietal lobule at rest compared to the control subjects. We found no significant correlation between the mean reaction time of the accurate responses in a 2-back task and the mean z-values within the regions that exhibited significant differences in RSFC at the individual level. The alterations in FCs of VWM-related network in lTLE suggested that epileptiform discharges can damage the brain regions, both local focus and remote areas and that the alterations were not associated with VWM performance. PMID:26101832

  3. PEGylated Carbon Nanotubes Impair Retrieval of Contextual Fear Memory and Alter Oxidative Stress Parameters in the Rat Hippocampus

    PubMed Central

    Dal Bosco, Lidiane; Weber, Gisele E. B.; Parfitt, Gustavo M.; Paese, Karina; Gonçalves, Carla O. F.; Serodre, Tiago M.; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

    2015-01-01

    Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions. PMID:25738149

  4. Concurrent and prospective associations of habitual overgeneral memory and prospection with symptoms of depression, general anxiety, obsessive compulsiveness, and post-traumatic stress.

    PubMed

    Boelen, Paul A; Huntjens, Rafaele J C; van den Hout, Marcel A

    2014-01-01

    Reduced memory specificity is associated with depression, post-traumatic stress disorder (PTSD), and some other forms of psychopathology. Reduced memory specificity is also associated with reduced specificity of envisioned future events. Research in this area has mostly relied on cue-word methods that include explicit instructions to develop specific memories of future events. These methods are limited in their ability to assess how participants habitually remember the past and imagine the future when the specificity constraints inherent in the cue-word task are removed. Sentence completions tasks have been developed that can be used to assess habitual patterns of memory and prospection. Little is known about the association of habitual memory and prospection with concurrently and prospectively assessed psychopathology. In the current study 142 participants completed sentence completion tasks tapping habitual memory and prospection at baseline and completed measures tapping psychological symptoms at baseline and 1 year later. Among other things, it was found that reduced memory specificity (but not reduced future specificity) was associated with concurrent and later depression, as well as with symptom levels of PTSD tapped 1 year beyond baseline.

  5. Purple grape juice as a protector against acute x-irradiation induced alterations on mobility, anxiety, and feeding behaviour in mice.

    PubMed

    Soares, Félix A A; Dalla Corte, Cristiane L; Andrade, Edson R; Marina, Raquel; González, Paquita; Barrio, Juan P

    2014-04-01

    The aim of this work was to test the hypothesis that a moderate intake of organic purple grape juice shows a positive radiomodifier effect over early behavioural damage following acute X-irradiation in mice. Anxiety-, locomotion-, and feeding-related responses to 6 Gy total body X-irradiation (TBI) were studied via open field, Rotarod, and feeding/drinking recording. Thirty-two male mice weighing 25-30 g were grouped according grape juice (J) or water (W) ad libitum drinking and either non-irradiated (N) or irradiated (R). 24 h post-TBI the access frequency to the center and corners of the open field was decreased, and the total stay in the corners increased, in RW vs. NW mice. Anxiety-related parameters decreased in RJ vs. RW mice. Rotarod latency times increased 72 h post-TBI in RJ vs RW mice. No overall changes in food and drink intake were observed along the experimental period. On the irradiation day, bout number was increased and bout duration was decreased in RW mice. The changes were reversed by purple grape juice intake. Grape juice intake before and after TBI can overcome several radiation-induced changes in behaviour within 24-72 hours after sub-lethal X-irradiation. This beneficial effect on short-term anxiety and mobilityrelated activities could probably be included in the list of flavonoid bio-effects. The present findings could be relevant in designing preventive interventions aimed to enhance body defense mechanisms against short-term irradiation damage.

  6. [Fundamental study of memory impairment and non-cognitive behavioral alterations in APPswe/PS1dE9 mice].

    PubMed

    Taniuchi, Nobuhiko; Niidome, Tetsuhiro; Sugimoto, Hachiro

    2015-01-01

    In addition to cognitive decline, Alzheimer's disease patients also exhibit non-cognitive symptoms commonly referred to as behavioral and psychological symptoms of dementia, or BPSD. These symptoms have a serious impact on the quality of life of these patients, as well as that of their caregivers, but there are currently no effective therapies. The amyloid β-peptide (Aβ) is suspected to play a central role in the cascade leading to Alzheimer's disease, but the precise mechanisms are still incompletely known. To assess the influence of Aβ pathology on cognitive and non-cognitive behaviors, we examined locomotor activity, motor coordination, and spatial memory in male and female APPswePS1dE9 mice (Alzheimer's disease model, double transgenic mice expressing an amyloid precursor protein with Swedish mutation and a presenilin-1 with deletion of exon 9) at 5 months of age, when the mice had subtle Aβ deposits, and again at 9 months of age, when the mice had numerous Aβ deposits. Compared to wild-type mice, the male and female APPswe/PS1dE9 mice showed normal motor coordination in the rotarod test at both 5 and 9 months. In the Morris water maze test, male and female APPswe/PS1dE9 mice showed impaired spatial memory at 9 months; however, no such deficits were found at 5 months. In a locomotor activity test, male APPswe/PS1dE9 mice exhibited locomotor hyperactivity at 9 months, while females exhibited locomotor hyperactivity at both 5 and 9 months compared to the control mice. Together, these results indicate that APPswe/PS1dE9 mice developed spatial memory impairment and BPSD-like behavioral alterations resulting from Aβ accumulation.

  7. Fatty acid induced metabolic memory involves alterations in renal histone H3K36me2 and H3K27me3.

    PubMed

    Kumar, Sandeep; Pamulapati, Himani; Tikoo, Kulbhushan

    2016-02-15

    Accumulating evidence suggest that diabetic complications persist even after the maintenance of normal glucose levels. However, the molecular mechanisms involved are still unclear. In the present study, we have investigated the molecular mechanism behind the presence of insulin resistance (IR) condition even after normalization of circulating lipids levels both in vivo and in vitro. Persistent inhibition of insulin signalling in absence of elevated circulating lipids level confirms the presence of metabolic memory in our model of IR. IR in human urine derived podocyte-like epithelial cells (HUPECs) was developed by incubating cells with palmitate (750 μM) for 24 h and in SD rats by feeding high fat diet for 16 weeks. Inhibition of insulin induced FOXO1 (regulator of gluconeogenic genes) degradation persisted even after 48 h of palmitate removal from the culture media. Metabolic memory by palmitate was found to be associated with increased FOXO1 activity as evident from increased expression of FOXO1 target genes such as PDK4, p21, G6Pc and IGFBP1. To understand the reason for prolonged activation of FOXO1 and its target genes, chromatin immuno-precipitation (ChIP) was performed with histone H3K36me2 and H3K27me3 antibodies. ChIP assay shows persistent increase in abundance of histone H3K36me2 on promoter region of FOXO1. We also show decreased abundance of histone H3K27me3 on promoter region of FOXO1, in the kidneys of HFD fed rats, which persisted even after 8 weeks of diet reversal. Taken together, we provide first evidence that circulating lipids generate metabolic memory possibly by altering the abundance of histone H3K36me2 and H3K27me3 on FOXO1 promoter.

  8. [Fundamental study of memory impairment and non-cognitive behavioral alterations in APPswe/PS1dE9 mice].

    PubMed

    Taniuchi, Nobuhiko; Niidome, Tetsuhiro; Sugimoto, Hachiro

    2015-01-01

    In addition to cognitive decline, Alzheimer's disease patients also exhibit non-cognitive symptoms commonly referred to as behavioral and psychological symptoms of dementia, or BPSD. These symptoms have a serious impact on the quality of life of these patients, as well as that of their caregivers, but there are currently no effective therapies. The amyloid β-peptide (Aβ) is suspected to play a central role in the cascade leading to Alzheimer's disease, but the precise mechanisms are still incompletely known. To assess the influence of Aβ pathology on cognitive and non-cognitive behaviors, we examined locomotor activity, motor coordination, and spatial memory in male and female APPswePS1dE9 mice (Alzheimer's disease model, double transgenic mice expressing an amyloid precursor protein with Swedish mutation and a presenilin-1 with deletion of exon 9) at 5 months of age, when the mice had subtle Aβ deposits, and again at 9 months of age, when the mice had numerous Aβ deposits. Compared to wild-type mice, the male and female APPswe/PS1dE9 mice showed normal motor coordination in the rotarod test at both 5 and 9 months. In the Morris water maze test, male and female APPswe/PS1dE9 mice showed impaired spatial memory at 9 months; however, no such deficits were found at 5 months. In a locomotor activity test, male APPswe/PS1dE9 mice exhibited locomotor hyperactivity at 9 months, while females exhibited locomotor hyperactivity at both 5 and 9 months compared to the control mice. Together, these results indicate that APPswe/PS1dE9 mice developed spatial memory impairment and BPSD-like behavioral alterations resulting from Aβ accumulation. PMID:25747232

  9. Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

    PubMed

    Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

    2015-06-01

    There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus.

  10. The Role of Ephs and Ephrins in Memory Formation

    PubMed Central

    Dines, Monica

    2016-01-01

    The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer’s disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. PMID:26371183

  11. Reduction of Methylphenidate Induced Anxiety, Depression and Cognition Impairment by Various doses of Venlafaxine in Rat

    PubMed Central

    Motaghinejad, Majid; Motevalian, Manijeh; Ebrahimzadeh, Andia; larijani, Setare Farokhi; Khajehamedi, Zohreh

    2015-01-01

    Background: Methylphenidate (MPH) is a neural stimulant agent, which its neurochemical and behavioral effect remain unclear. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor antidepressant, which was used for management of depression and anxiety. In this study, protective effects of venlafaxine on MPH induced anxiety, depression and cognition impairment were investigated. Methods: Forty-eight adult male rats were divided randomly to 5 groups. Group 1, received normal saline (0.2 ml/rat) for 21 days and served as control group. Group 2, received MPH (10 mg/kg) for 21 days. Groups, 3, 4, 5 and 6 concurrently were treated by MPH (10 mg/kg) and venlafaxine at doses of 25, 50, 75 and 100 mg/kg respectively for 21 days. On day 22, elevated plus maze (EPM), open field test (OFT), forced swim test (FST) and tail suspension test (TST) were used to investigate the level of anxiety and depression in animals. In addition, between days 17 and 21, Morris water maze (MWM) was used to evaluate the effect of MPH on spatial learning and memory. Results: MPH caused depression and anxiety in a dose-dependent manner in FST, OFT, EPM and TST, which were significantly different compared with control group. Furthermore, MPH can significantly attenuate the motor activity in OFT. Venlafaxine in all doses can attenuate MPH induced anxiety, depression and motor activity alterations. MPH also can disturb learning and memory in MWM, but venlafaxine did not alter this effect of MPH. Conclusions: We conclude that venlafaxine can be protective in the brain against MPH induced anxiety and depression. PMID:26124949

  12. Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ERα, ERβ), oxytocin and serotonin (5-HT1A) in their brain.

    PubMed

    Stamatakis, Antonios; Kalpachidou, Theodora; Raftogianni, Androniki; Zografou, Efstratia; Tzanou, Athanasia; Pondiki, Stavroula; Stylianopoulou, Fotini

    2015-02-01

    In the present study we investigated the neurobiological mechanisms underlying expression of maternal behavior. Increased maternal behavior was experimentally induced by a brief 15-min separation between the mother and the pups during postnatal days 1 to 22. On postnatal days (PND) 12 and 22, we determined in experimental and control dams levels of anxiety in the elevated plus maze (EPM) as well as the levels of receptors for estrogens (ERα, ERβ), oxytocin (OTR) and serotonin (5-HT1AR) in areas of the limbic system (prefrontal cortex-PFC, hippocampus, lateral septum-SL, medial preoptic area-MPOA, shell of nucleus accumbens-nAc-Sh, central-CeA and basolateral-BLA amygdala), involved in the regulation of maternal behavior. Experimental dams, which showed increased maternal behavior towards their offspring, displayed reduced anxiety in the EPM on both PND12 and PND22. These behavioral differences could be attributed to neurochemical alterations in their brain: On both PND12 and PND22, experimental mothers had higher levels of ERα and OTRs in the PFC, hippocampus, CeA, SL, MPOA and nAc-Sh. The experimental manipulation-induced increase in ERβ levels was less widespread, being localized in PFC, the hippocampal CA2 area, MPOA and nAc-Sh. In addition, 5-HT1ARs were reduced in the PFC, hippocampus, CeA, MPOA and nAc-Sh of the experimental mothers. Our results show that the experience of the daily repeated brief separation from the pups results in increased brain ERs and OTRs, as well as decreased 5-HT1ARs in the dam's brain; these neurochemical changes could underlie the observed increase in maternal behavior and the reduction of anxiety.

  13. Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.

    PubMed

    Kline, R H; Exposto, F G; O'Buckley, S C; Westlund, K N; Nackley, A G

    2015-04-01

    Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10-45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of βARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites.

  14. Catechol-O-methlytransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat

    PubMed Central

    Kline, R. H.; Exposto, F. G.; O’Buckley, S. C.; Westlund, K. N.; Nackley, A. G.

    2015-01-01

    Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10–45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of ARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites. PMID:25659347

  15. Differences between effects of psychological versus pharmacological treatments on functional and morphological brain alterations in anxiety disorders and major depressive disorder: a systematic review.

    PubMed

    Quidé, Yann; Witteveen, Anke B; El-Hage, Wissam; Veltman, Dick J; Olff, Miranda

    2012-01-01

    The most prevalent mental disorders, anxiety and mood disorders, are associated with both functional and morphological brain changes that commonly involve the 'fear network' including the (medial) prefrontal cortex, hippocampus and amygdala. Patients suffering from anxiety disorders and major depressive disorder often show excessive amygdala and reduced prefrontal cortex functioning. It is, however, still unclear whether these brain abnormalities disappear or diminish following effective treatment. This review aims to compare the effects of psychotherapy and pharmacotherapy on functional and morphological brain measures in these disorders. Sixty-three studies were included, 30 investigating psychotherapy effects and 33 investigating pharmacotherapy effects. Despite methodological differences, results suggest a functional normalization of the 'fear network'. Pharmacotherapy particularly decreases over-activity of limbic structures (bottom-up effect) while psychotherapy tends to increase activity and recruitment of frontal areas (top-down effect), especially the anterior cingulate cortex. Additionally, pharmacotherapy, but not psychotherapy, has been associated with morphological changes, depending on the disorder. These findings suggest that both types of treatments normalize (functional) brain abnormalities each in specific ways.

  16. Angiotensin II disrupts inhibitory avoidance memory retrieval.

    PubMed

    Bonini, Juliana S; Bevilaqua, Lia R; Zinn, Carolina G; Kerr, Daniel S; Medina, Jorge H; Izquierdo, Iván; Cammarota, Martín

    2006-08-01

    The brain renin-angiotensin system (RAS) is involved in learning and memory, but the actual role of angiotensin II (A(II)) and its metabolites in this process has been difficult to comprehend. This has been so mainly due to procedural issues, especially the use of multi-trial learning paradigms and the utilization of pre-training intracerebroventricular infusion of RAS-acting compounds. Here, we specifically analyzed the action of A(II) in aversive memory retrieval using a hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Rats bilaterally implanted with infusion cannulae aimed to the CA1 region of the dorsal hippocampus were trained in IA and tested for memory retention 24 h later. We found that when given into CA1 15 min before IA memory retention test, A(II), but not angiotensin IV or angiotensin(1-7) induced a dose-dependent and reversible amnesia without altering locomotor activity, exploratory behavior or anxiety state. The effect of A(II) was blocked in a dose-dependent manner by the A(II)-type 2 receptor (AT(2)) antagonist PD123319 but not by the A(II)-type 1 receptor (AT(1)) antagonist losartan. By themselves, neither PD123319 nor losartan had any effect on memory expression. Our data indicate that intra-CA1 A(II) hinders retrieval of avoidance memory through a process that involves activation of AT(2) receptors.

  17. Anxiety Disorders.

    ERIC Educational Resources Information Center

    Dickey, Marilyn

    Anxiey, in general, helps one to cope. It rouses a person to action and gears one up to face a threatening situation. It makes students study harder for exams, and keeps presenters on their toes when making speeches. But an anxiety disorder can prevent one from coping and can disrupt daily life. Anxiety disorders are not just a case of "nerves,"…

  18. Math anxiety differentially affects WAIS-IV arithmetic performance in undergraduates.

    PubMed

    Buelow, Melissa T; Frakey, Laura L

    2013-06-01

    Previous research has shown that math anxiety can influence the math performance level; however, to date, it is unknown whether math anxiety influences performance on working memory tasks during neuropsychological evaluation. In the present study, 172 undergraduate students completed measures of math achievement (the Math Computation subtest from the Wide Range Achievement Test-IV), math anxiety (the Math Anxiety Rating Scale-Revised), general test anxiety (from the Adult Manifest Anxiety Scale-College version), and the three Working Memory Index tasks from the Wechsler Adult Intelligence Scale-IV Edition (WAIS-IV; Digit Span [DS], Arithmetic, Letter-Number Sequencing [LNS]). Results indicated that math anxiety predicted performance on Arithmetic, but not DS or LNS, above and beyond the effects of gender, general test anxiety, and math performance level. Our findings suggest that math anxiety can negatively influence WAIS-IV working memory subtest scores. Implications for clinical practice include the utilization of LNS in individuals expressing high math anxiety.

  19. Prenatal exposure to alcohol and 3,4-methylenedioxymethamphetamine (ecstasy) alters adult hippocampal neurogenesis and causes enduring memory deficits.

    PubMed

    Canales, Juan J; Ferrer-Donato, Agueda

    2014-01-01

    Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.

  20. Anxiety and classroom examination performance.

    PubMed

    Daniels, B; Hewitt, J

    1978-04-01

    Studied classroom examination performance over the course of an entire semester as a function of (a) students' anxiety level (high, medium, low); (b) difficulty level of exam question (more vs. less difficult); (c) type of exam question (rote memory vs. generalization); (d) sex of S; and (e) intelligence level of S. As expected, there was a strong main effect of anxiety and a significant interaction between anxiety and item difficulty. The latter was consistent with the Hull-Spence formulation of learning and performance--as the habit strength of incorrect responses increases (i.e., as the items become more difficult), the superiority of low over high anxious Ss also should increase. When item difficulty was held constant, anxiety did not interact with type of exam question. PMID:681509

  1. Effects of Cortisol on Reconsolidation of Reactivated Fear Memories.

    PubMed

    Drexler, Shira Meir; Merz, Christian J; Hamacher-Dang, Tanja C; Tegenthoff, Martin; Wolf, Oliver T

    2015-12-01

    The return of conditioned fear after successful extinction (eg, following exposure therapy) is a significant problem in the treatment of anxiety disorders and posttraumatic stress disorder (PTSD). Targeting the reconsolidation of fear memories may allow a more lasting effect as it intervenes with the original memory trace. Indeed, several pharmacological agents and behavioral interventions have been shown to alter (enhance, impair, or otherwise update) the reconsolidation of reactivated memories of different types. Cortisol is a stress hormone and a potent modulator of learning and memory, yet its effects on fear memory reconsolidation are unclear. To investigate whether cortisol intervenes with the reconsolidation of fear memories in healthy males and how specific this effect might be, we built a 3-day reconsolidation design with skin conductance response (SCR) as a measure of conditioned fear: Fear acquisition on day 1; reactivation/no-reactivation of one conditioned stimulus and pharmacological intervention on day 2; extinction learning followed by reinstatement and reinstatement test on day 3. The groups differed only in the experimental manipulation on day 2: Reactivation+Cortisol Group, Reactivation+Placebo Group, or No-reactivation+Cortisol Group. Our results revealed an enhancing effect of cortisol on reconsolidation of the reactivated memory. The effect was highly specific, strengthening only the memory of the reactivated conditioned stimulus and not the non-reactivated one. Our findings are in line with previous findings showing an enhancing effect of behavioral stress on the reconsolidation of other types of memories. These results have implications for the understanding and treatment of anxiety disorders and PTSD. PMID:26058664

  2. Effects of Cortisol on Reconsolidation of Reactivated Fear Memories.

    PubMed

    Drexler, Shira Meir; Merz, Christian J; Hamacher-Dang, Tanja C; Tegenthoff, Martin; Wolf, Oliver T

    2015-12-01

    The return of conditioned fear after successful extinction (eg, following exposure therapy) is a significant problem in the treatment of anxiety disorders and posttraumatic stress disorder (PTSD). Targeting the reconsolidation of fear memories may allow a more lasting effect as it intervenes with the original memory trace. Indeed, several pharmacological agents and behavioral interventions have been shown to alter (enhance, impair, or otherwise update) the reconsolidation of reactivated memories of different types. Cortisol is a stress hormone and a potent modulator of learning and memory, yet its effects on fear memory reconsolidation are unclear. To investigate whether cortisol intervenes with the reconsolidation of fear memories in healthy males and how specific this effect might be, we built a 3-day reconsolidation design with skin conductance response (SCR) as a measure of conditioned fear: Fear acquisition on day 1; reactivation/no-reactivation of one conditioned stimulus and pharmacological intervention on day 2; extinction learning followed by reinstatement and reinstatement test on day 3. The groups differed only in the experimental manipulation on day 2: Reactivation+Cortisol Group, Reactivation+Placebo Group, or No-reactivation+Cortisol Group. Our results revealed an enhancing effect of cortisol on reconsolidation of the reactivated memory. The effect was highly specific, strengthening only the memory of the reactivated conditioned stimulus and not the non-reactivated one. Our findings are in line with previous findings showing an enhancing effect of behavioral stress on the reconsolidation of other types of memories. These results have implications for the understanding and treatment of anxiety disorders and PTSD.

  3. Overview of generalized anxiety disorder in the elderly.

    PubMed

    Schneider, L S

    1996-01-01

    Both situational anxiety and pathologic anxiety are common in the elderly. Pathologic anxiety, however, may significantly disable a previously functioning older adult. Moderate-to-severe anxiety is important to accurately diagnose and treat in older persons in order to improve daily functioning and because individual symptoms of anxiety can be easily confused with even more severe geropsychiatric disorders such as dementia, delirium, depression, and psychosis. These particular symptoms include impaired concentration and attention, impaired memory, dizziness, disabling fear, severe insomnia, and hypervigilance, among others. This article will review epidemiology, characteristics of anxiety in late-life, patterns of medication use, and treatment. PMID:8690696

  4. [The elderly and memory complaints. A study of self-knowledge about memory, depression and memory abilities].

    PubMed

    Ponds, R W; Bruning, H A; Jolles, J

    1992-10-01

    A group of 24 elderly persons who applied for a memory training because of memory complaints is compared with a control group of 24 healthy persons (matched for age, sex, and education). The comparison concerned several memory tests, complaints above everyday memory, depression and aspects of meta-memory. Before training, the memory training group had more complaints about everyday memory and depression compared to the control group. The training group reported more decline in memory capacity and functioning compared to their earlier days. They also reported feelings of stress and anxiety related to memory performance in daily life. Before training, the training group had more general knowledge about basic memory processes and used memory strategies more frequently. On most memory tests no differences were found. Memory complaints of elderly people may therefore not only be related to memory abilities according to tests but also to individual (negative) beliefs in memory capacity and abilities. PMID:1440759

  5. Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species.

    PubMed

    Villasana, Laura E; Weber, Sydney; Akinyeke, Tunde; Raber, Jacob

    2016-09-01

    Apolipoprotein E (apoE), involved in cholesterol and lipid metabolism, also influences cognitive function and injury repair. In humans, apoE is expressed in three isoforms. E4 is a risk factor for age-related cognitive decline and Alzheimer's disease, particularly in women. E4 might also be a risk factor for developing behavioral and cognitive changes following (56) Fe irradiation, a component of the space environment astronauts are exposed to during missions. These changes might be related to enhanced generation of reactive oxygen species (ROS). In this study, we compared the behavioral and cognitive performance of sham-irradiated and irradiated wild-type (WT) mice and mice expressing the human E3 or E4 isoforms, and assessed the generation of ROS in hippocampal slices from these mice. E4 mice had greater anxiety-like and conditioned fear behaviors than WT mice, and these genotype differences were associated with greater levels of ROS in E4 than WT mice. The greater generation of ROS in the hippocampus of E4 than WT mice might contribute to their higher anxiety levels and enhanced fear conditioning. In E4, but not WT, mice, phorbol-12-myristate-13-acetate-treated hippocampal slices showed more dihydroxy ethidium oxidation in sham-irradiated than irradiated mice and hippocampal heme oxygenase-1 levels were higher in irradiated than sham-irradiated E4 mice. Mice with apolipoprotein E4 (E4), a risk factor for Alzheimer's disease, have greater anxiety-like and conditioned fear behaviors than wild-type (WT) mice. Generation of reactive oxygen species (ROS, in red) 3 months following (56) Fe irradiation, a component of the space environment astronauts are exposed to, is more pronounced in the hippocampus of E4 than WT mice. In E4, but not WT, mice, hippocampal levels of the oxidative stress-relevant marker heme oxygenase-1 are higher in irradiated than sham-irradiated E4 mice. PMID:27412623

  6. Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species.

    PubMed

    Villasana, Laura E; Weber, Sydney; Akinyeke, Tunde; Raber, Jacob

    2016-09-01

    Apolipoprotein E (apoE), involved in cholesterol and lipid metabolism, also influences cognitive function and injury repair. In humans, apoE is expressed in three isoforms. E4 is a risk factor for age-related cognitive decline and Alzheimer's disease, particularly in women. E4 might also be a risk factor for developing behavioral and cognitive changes following (56) Fe irradiation, a component of the space environment astronauts are exposed to during missions. These changes might be related to enhanced generation of reactive oxygen species (ROS). In this study, we compared the behavioral and cognitive performance of sham-irradiated and irradiated wild-type (WT) mice and mice expressing the human E3 or E4 isoforms, and assessed the generation of ROS in hippocampal slices from these mice. E4 mice had greater anxiety-like and conditioned fear behaviors than WT mice, and these genotype differences were associated with greater levels of ROS in E4 than WT mice. The greater generation of ROS in the hippocampus of E4 than WT mice might contribute to their higher anxiety levels and enhanced fear conditioning. In E4, but not WT, mice, phorbol-12-myristate-13-acetate-treated hippocampal slices showed more dihydroxy ethidium oxidation in sham-irradiated than irradiated mice and hippocampal heme oxygenase-1 levels were higher in irradiated than sham-irradiated E4 mice. Mice with apolipoprotein E4 (E4), a risk factor for Alzheimer's disease, have greater anxiety-like and conditioned fear behaviors than wild-type (WT) mice. Generation of reactive oxygen species (ROS, in red) 3 months following (56) Fe irradiation, a component of the space environment astronauts are exposed to, is more pronounced in the hippocampus of E4 than WT mice. In E4, but not WT, mice, hippocampal levels of the oxidative stress-relevant marker heme oxygenase-1 are higher in irradiated than sham-irradiated E4 mice.

  7. Anxiety Disorders

    MedlinePlus

    ... fearful to talk at all in certain situations. Panic attacks. These episodes of anxiety can occur for no apparent reason. During a panic attack, a child typically has sudden and intense physical ...

  8. Intergroup anxiety effects on implicit racial evaluation and stereotyping.

    PubMed

    Amodio, David M; Hamilton, Holly K

    2012-12-01

    How does intergroup anxiety affect the activation of implicit racial evaluations and stereotypes? Given the common basis of social anxiety and implicit evaluative processes in memory systems linked to classical conditioning and affect, we predicted that intergroup anxiety would amplify implicit negative racial evaluations. Implicit stereotyping, which is associated primarily with semantic memory systems, was not expected to increase as a function of intergroup anxiety. This pattern was observed among White participants preparing to interact with Black partners, but not those preparing to interact with White partners. These findings shed new light on how anxiety, often elicited in real-life intergroup interactions, can affect the operation of implicit racial biases, suggesting that intergroup anxiety has more direct implications for affective and evaluative forms of implicit bias than for implicit stereotyping. These findings also support a memory-systems model of the interplay between emotion and cognition in the context of social behavior.

  9. Fear Memory.

    PubMed

    Izquierdo, Ivan; Furini, Cristiane R G; Myskiw, Jociane C

    2016-04-01

    Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general. PMID:26983799

  10. Fear Memory.

    PubMed

    Izquierdo, Ivan; Furini, Cristiane R G; Myskiw, Jociane C

    2016-04-01

    Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

  11. Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: An ICA-based analysis

    PubMed Central

    Zhang, Yang; Lu, Shan; Liu, Chunlei; Zhang, Huimei; Zhou, Xuanhe; Ni, Changlin; Qin, Wen; Zhang, Quan

    2016-01-01

    Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits, among which working memory (WM) is usually involved at an early stage. However, the neural substrates underlying impaired WM in T2DM patients are still unclear. To clarify this issue, we utilized functional magnetic resonance imaging (fMRI) and independent component analysis to evaluate T2DM patients for alterations in brain activation and functional connectivity (FC) in WM networks and to determine their associations with cognitive and clinical variables. Twenty complication-free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI data were acquired during a block-designed 1-back WM task. The WM metrics of the T2DM patients showed no differences compared with those of the HCs, except for a slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the T2DM patients demonstrated increased activation within their WM fronto-parietal networks, and activation strength was significantly correlated with WM performance. The T2DM patients also showed decreased FC within and between their WM networks. Our results indicate that the functional integration of WM sub-networks was disrupted in the complication-free T2DM patients and that strengthened regional activity in fronto-parietal networks may compensate for the WM impairment caused by T2DM. PMID:27021340

  12. Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

    PubMed

    Jiang, Yong-Hui; Pan, Yanzhen; Zhu, Li; Landa, Luis; Yoo, Jong; Spencer, Corinne; Lorenzo, Isabel; Brilliant, Murray; Noebels, Jeffrey; Beaudet, Arthur L

    2010-08-20

    Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal

  13. Emotion-Induced Retrograde Amnesia and Trait Anxiety

    ERIC Educational Resources Information Center

    Miu, Andrei C.; Heilman, Renata M.; Opre, Adrian; Miclea, Mircea

    2005-01-01

    Emotional arousal can both enhance and impair memory. Considering that both emotional memory and trait anxiety (TA) have been associated with adrenergic activity, the authors investigated whether there is an association between 2 opposite emotional memory biases and the TA. The authors used a procedure recently put forward by B. A. Strange, R.…

  14. Modulatory mechanisms of cortisol effects on emotional learning and memory: novel perspectives.

    PubMed

    van Ast, Vanessa A; Cornelisse, Sandra; Marin, Marie-France; Ackermann, Sandra; Garfinkel, Sarah N; Abercrombie, Heather C

    2013-09-01

    It has long been known that cortisol affects learning and memory processes. Despite a wealth of research dedicated to cortisol effects on learning and memory, the strength or even directionality of the effects often vary. A number of the factors that alter cortisol's effects on learning and memory are well-known. For instance, effects of cortisol can be modulated by emotional arousal and the memory phase under study. Despite great advances in understanding factors that explain variability in cortisol's effects, additional modulators of cortisol effects on memory exist that are less widely acknowledged in current basic experimental research. The goal of the current review is to disseminate knowledge regarding less well-known modulators of cortisol effects on learning and memory. Since several models for the etiology of anxiety, such as post-traumatic stress disorder (PTSD), incorporate stress and the concomitant release of cortisol as important vulnerability factors, enhanced understanding of mechanisms by which cortisol exerts beneficial as opposed to detrimental effects on memory is very important. Further elucidation of the factors that modulate (or alter) cortisol's effects on memory will allow reconciliation of seemingly inconsistent findings in the basic and clinical literatures. The present review is based on a symposium as part of the 42nd International Society of Psychoneuroendocrinology Conference, New York, USA, that highlighted some of those modulators and their underlying mechanisms.

  15. Emotional reasoning and anxiety sensitivity: Associations with social anxiety disorder in childhood☆

    PubMed Central

    Alkozei, Anna; Cooper, Peter J.; Creswell, Cathy

    2014-01-01

    Background Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object. Method The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7–12 years). Results Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios. Limitations This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution. Conclusion The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders. PMID:24120086

  16. Activation of 5-HT2a Receptors in the Basolateral Amygdala Promotes Defeat-Induced Anxiety and the Acquisition of Conditioned Defeat in Syrian Hamsters

    PubMed Central

    Clinard, Catherine T.; Bader, Lauren R.; Sullivan, Molly A.; Cooper, Matthew A.

    2014-01-01

    Conditioned defeat is a model in Syrian hamsters (Mesocricetus auratus) in which normal territorial aggression is replaced by increased submissive and defensive behavior following acute social defeat. The conditioned defeat response involves both a fear-related memory for a specific opponent as well as anxiety-like behavior indicated by avoidance of novel conspecifics. We have previously shown that systemic injection of a 5-HT2a receptor antagonist reduces the acquisition of conditioned defeat. Because neural activity in the basolateral amygdala (BLA) is critical for the acquisition of conditioned defeat and BLA 5-HT2a receptors can modulate anxiety but have a limited effect on emotional memories, we investigated whether 5-HT2a receptor modulation alters defeat-induced anxiety but not defeat-related memories. We injected the 5-HT2a receptor antagonist MDL 11,939 (0 mM, 1.7 mM or 17 mM) or the 5-HT2a receptor agonist TCB-2 (0 mM, 8 mM or 80 mM) into the BLA prior to social defeat. We found that injection of MDL 11,939 into the BLA impaired acquisition of the conditioned defeat response and blocked defeat-induced anxiety in the open field, but did not significantly impair avoidance of former opponents in the Y-maze. Furthermore, we found that injection of TCB-2 into the BLA increased the acquisition of conditioned defeat and increased anxiety-like behavior in the open field, but did not alter avoidance of former opponents. Our data suggest that 5-HT2a receptor signaling in the BLA is both necessary and sufficient for the development of conditioned defeat, likely via modulation of defeat-induced anxiety. PMID:25458113

  17. Sex differences in anxiety and emotional behavior

    PubMed Central

    Donner, Nina C.; Lowry, Christopher A.

    2013-01-01

    Research has elucidated causal links between stress exposure and the development of anxiety disorders, but due to the limited use of female or sex-comparative animal models, little is known about the mechanisms underlying sex differences in those disorders. This is despite an overwhelming wealth of evidence from the clinical literature that the prevalence of anxiety disorders is about twice as high in women compared to men, in addition to gender differences in severity and treatment efficacy. We here review human gender differences in generalized anxiety disorder, panic disorder, posttraumatic stress disorder and anxiety-relevant biological functions, discuss the limitations of classic conflict anxiety tests to measure naturally occurring sex differences in anxiety-like behaviors, describe sex-dependent manifestation of anxiety states after gestational, neonatal, or adolescent stressors, and present animal models of chronic anxiety states induced by acute or chronic stressors during adulthood. Potential mechanisms underlying sex differences in stress-related anxiety states include emerging evidence supporting the existence of two anatomically and functionally distinct serotonergic circuits that are related to the modulation of conflict anxiety and panic-like anxiety, respectively. We discuss how these serotonergic circuits may be controlled by reproductive steroid hormone-dependent modulation of crfr1 and crfr2 expression in the midbrain dorsal raphe nucleus and by estrous stage-dependent alterations of γ-aminobutyric acid (GABAergic) neurotransmission in the periaqueductal gray, ultimately leading to sex differences in emotional behavior. PMID:23588380

  18. Ambiguity in the Manifestation of Adult Separation Anxiety Disorder Occurring in Complex Anxiety Presentations: Two Clinical Case Reports

    ERIC Educational Resources Information Center

    Dudaee-Faass, Sigal; Marnane, Claire; Wagner, Renate

    2009-01-01

    Two case reports are described in which patients presented for the treatment of multiple comorbid anxiety disorders, all of which appeared to derive from prolonged separation anxiety disorder. In particular, these adults had effectively altered their lifestyles to avoid separation, thereby displaying only ambiguous separation anxiety symptoms that…

  19. Neuronal histamine and the interplay of memory, reinforcement and emotions.

    PubMed

    Dere, E; Zlomuzica, A; De Souza Silva, M A; Ruocco, L A; Sadile, A G; Huston, J P

    2010-12-31

    The biogenic amine histamine is an important neurotransmitter-neuromodulator in the central nervous system that has been implicated in a variety of biological functions including thermo- and immunoregulation, food intake, seizures, arousal, anxiety, reward and memory. The review of the pertinent literature indicates that the majority of findings are compatible with the appraisal that the inhibition of histaminergic neurotransmission impairs learning and memory formation, decreases cortical activation and arousal, has a suppressive effect on behavioral measures of fear and anxiety, exponentiates the rewarding effects of drugs of abuse and intracranial brain stimulation. In contrast, the stimulation of histaminergic neurotransmission can ameliorate learning and memory impairments that are associated with various experimental deficit models and pathological conditions. Clinical investigations with patients suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's disease demonstrate pathological alterations in the brain's histaminergic system, which, in some cases are correlated with the severity of cognitive deficits. The role of the brain's histamine system in episodic memory formation and the potential of histamine-related drugs to ameliorate cognitive deficits in early stages of neurodegenerative diseases are discussed.

  20. 17β-estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas.

    PubMed

    Kiss, Agata; Delattre, Ana Márcia; Pereira, Sofia I R; Carolino, Ruither G; Szawka, Raphael E; Anselmo-Franci, Janete A; Zanata, Sílvio M; Ferraz, Anete C

    2012-02-01

    Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17β-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17β-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17β-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17β-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17β-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline.

  1. Implication of Genetic Deletion of Wdr13 in Mice: Mild Anxiety, Better Performance in Spatial Memory Task, with Upregulation of Multiple Synaptic Proteins.

    PubMed

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S; Tiwari, Vivek; Lakshmi, B Jyothi; Thakur, Suman S; Kumar, Satish

    2016-01-01

    WDR13 expresses from the X chromosome and has a highly conserved coding sequence. There have been multiple associations of WDR13 with memory. However, its detailed function in context of brain and behavior remains unknown. We characterized the behavioral phenotype of 2 month old male mice lacking the homolog of WDR13 gene (Wdr13 (-/0)). Taking cue from analysis of its expression in the brain, we chose hippocampus for molecular studies to delineate its function. Wdr13 (-/0) mice spent less time in the central area of the open field test (OFT) and with the novel object in novel object recognition test (NOR) as compared to the wild-type. However, these mice didn't show any significant changes in total time spent in arms or in frequency of arm entries in elevated plus maze (EPM). In the absence of Wdr13, there was a significant upregulation of synaptic proteins, viz., SYN1, RAB3A, CAMK2A etc. accompanied with increased spine density of hippocampal CA1 neurons and better spatial memory in mice as measured by increased time spent in the target quadrant of Morris water maze (MWM) during probe test. Parallel study from our lab has established c-JUN, ER α/β, and HDAC 1,3,7 as interacting partners of WDR13. WDR13 represses transcription from AP1 (c-JUN responsive) and Estrogen Receptor Element (ERE) promoters. We hypothesized that absence of Wdr13 would result in de-regulated expression of a number of genes including multiple synaptic genes leading to the observed phenotype. Knocking down Wdr13 in Neuro2a cell lines led to increased transcripts of Camk2a and Nrxn2 consistent with in-vivo results. Summarily, our data provides functional evidence for the role of Wdr13 in brain. PMID:27625594

  2. Implication of Genetic Deletion of Wdr13 in Mice: Mild Anxiety, Better Performance in Spatial Memory Task, with Upregulation of Multiple Synaptic Proteins

    PubMed Central

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Tiwari, Vivek; Lakshmi, B. Jyothi; Thakur, Suman S.; Kumar, Satish

    2016-01-01

    WDR13 expresses from the X chromosome and has a highly conserved coding sequence. There have been multiple associations of WDR13 with memory. However, its detailed function in context of brain and behavior remains unknown. We characterized the behavioral phenotype of 2 month old male mice lacking the homolog of WDR13 gene (Wdr13−/0). Taking cue from analysis of its expression in the brain, we chose hippocampus for molecular studies to delineate its function. Wdr13−/0 mice spent less time in the central area of the open field test (OFT) and with the novel object in novel object recognition test (NOR) as compared to the wild-type. However, these mice didn't show any significant changes in total time spent in arms or in frequency of arm entries in elevated plus maze (EPM). In the absence of Wdr13, there was a significant upregulation of synaptic proteins, viz., SYN1, RAB3A, CAMK2A etc. accompanied with increased spine density of hippocampal CA1 neurons and better spatial memory in mice as measured by increased time spent in the target quadrant of Morris water maze (MWM) during probe test. Parallel study from our lab has established c-JUN, ER α/β, and HDAC 1,3,7 as interacting partners of WDR13. WDR13 represses transcription from AP1 (c-JUN responsive) and Estrogen Receptor Element (ERE) promoters. We hypothesized that absence of Wdr13 would result in de-regulated expression of a number of genes including multiple synaptic genes leading to the observed phenotype. Knocking down Wdr13 in Neuro2a cell lines led to increased transcripts of Camk2a and Nrxn2 consistent with in-vivo results. Summarily, our data provides functional evidence for the role of Wdr13 in brain. PMID:27625594

  3. Implication of Genetic Deletion of Wdr13 in Mice: Mild Anxiety, Better Performance in Spatial Memory Task, with Upregulation of Multiple Synaptic Proteins

    PubMed Central

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Tiwari, Vivek; Lakshmi, B. Jyothi; Thakur, Suman S.; Kumar, Satish

    2016-01-01

    WDR13 expresses from the X chromosome and has a highly conserved coding sequence. There have been multiple associations of WDR13 with memory. However, its detailed function in context of brain and behavior remains unknown. We characterized the behavioral phenotype of 2 month old male mice lacking the homolog of WDR13 gene (Wdr13−/0). Taking cue from analysis of its expression in the brain, we chose hippocampus for molecular studies to delineate its function. Wdr13−/0 mice spent less time in the central area of the open field test (OFT) and with the novel object in novel object recognition test (NOR) as compared to the wild-type. However, these mice didn't show any significant changes in total time spent in arms or in frequency of arm entries in elevated plus maze (EPM). In the absence of Wdr13, there was a significant upregulation of synaptic proteins, viz., SYN1, RAB3A, CAMK2A etc. accompanied with increased spine density of hippocampal CA1 neurons and better spatial memory in mice as measured by increased time spent in the target quadrant of Morris water maze (MWM) during probe test. Parallel study from our lab has established c-JUN, ER α/β, and HDAC 1,3,7 as interacting partners of WDR13. WDR13 represses transcription from AP1 (c-JUN responsive) and Estrogen Receptor Element (ERE) promoters. We hypothesized that absence of Wdr13 would result in de-regulated expression of a number of genes including multiple synaptic genes leading to the observed phenotype. Knocking down Wdr13 in Neuro2a cell lines led to increased transcripts of Camk2a and Nrxn2 consistent with in-vivo results. Summarily, our data provides functional evidence for the role of Wdr13 in brain.

  4. Psychopharmacology and memory

    PubMed Central

    Glannon, W

    2006-01-01

    Psychotropic and other drugs can alter brain mechanisms regulating the formation, storage, and retrieval of different types of memory. These include “off label” uses of existing drugs and new drugs designed specifically to target the neural bases of memory. This paper discusses the use of beta‐adrenergic antagonists to prevent or erase non‐conscious pathological emotional memories in the amygdala. It also discusses the use of novel psychopharmacological agents to enhance long term semantic and short term working memory by altering storage and retrieval mechanisms in the hippocampus and prefrontal cortex. Although intervention in the brain to alter memory as therapy or enhancement holds considerable promise, the long term effects of experimental drugs on the brain and memory are not known. More studies are needed to adequately assess the potential benefits and risks of these interventions. PMID:16446410

  5. Ancient Anxiety Pathways Influence Drosophila Defense Behaviors

    PubMed Central

    Mohammad, Farhan; Aryal, Sameer; Ho, Joses; Stewart, James Charles; Norman, Nurul Ayuni; Tan, Teng Li; Eisaka, Agnese; Claridge-Chang, Adam

    2016-01-01

    Summary Anxiety helps us anticipate and assess potential danger in ambiguous situations [1, 2, 3]; however, the anxiety disorders are the most prevalent class of psychiatric illness [4, 5, 6]. Emotional states are shared between humans and other animals [7], as observed by behavioral manifestations [8], physiological responses [9], and gene conservation [10]. Anxiety research makes wide use of three rodent behavioral assays—elevated plus maze, open field, and light/dark box—that present a choice between sheltered and exposed regions [11]. Exposure avoidance in anxiety-related defense behaviors was confirmed to be a correlate of rodent anxiety by treatment with known anxiety-altering agents [12, 13, 14] and is now used to characterize anxiety systems. Modeling anxiety with a small neurogenetic animal would further aid the elucidation of its neuronal and molecular bases. Drosophila neurogenetics research has elucidated the mechanisms of fundamental behaviors and implicated genes that are often orthologous across species. In an enclosed arena, flies stay close to the walls during spontaneous locomotion [15, 16], a behavior proposed to be related to anxiety [17]. We tested this hypothesis with manipulations of the GABA receptor, serotonin signaling, and stress. The effects of these interventions were strikingly concordant with rodent anxiety, verifying that these behaviors report on an anxiety-like state. Application of this method was able to identify several new fly anxiety genes. The presence of conserved neurogenetic pathways in the insect brain identifies Drosophila as an attractive genetic model for the study of anxiety and anxiety-related disorders, complementing existing rodent systems. PMID:27020741

  6. Anxiety in older adults often goes undiagnosed.

    PubMed

    Koychev, Ivan; Ebmeier, Klaus P

    2016-01-01

    Anxiety disorder in the elderly is twice as common as dementia and four to six times more common than major depression. Anxiety is associated with poorer quality of life, significant distress and contributes to the onset of disability. Mortality risks are also increased, through physical causes, especially cardiovascular disease, and suicide. Diagnosing anxiety disorders in older adults remains a challenge because of the significant overlap in symptoms between physical disorders (shortness of breath; abdominal and chest pain; palpitations) and depression (disturbed sleep; poor attention, concentration and memory; restlessness). Good history taking is crucial in elucidating whether the complaint is of new onset or a recurrence of a previous disorder. The presence of comorbid depression should be clarified. If present, its temporal relationship with the anxiety symptoms will indicate whether there is an independent anxiety disorder. A medication review is warranted, as a number of drugs may be causative (calcium channel blockers, alpha- and beta-blockers, digoxin, L-thyroxine, bronchodilators, steroids, theophylline, antihistamines) or may cause anxiety in withdrawal (e.g. benzodiazepines). Substance and alcohol abuse should be excluded, as withdrawal from either may cause anxiety. A new or exacerbated physical illness may be related to anxiety. Medical investigations will help clarify the extent to which a particular somatic symptom is the result of anxiety. PMID:27180498

  7. Anxious mood and memory.

    PubMed

    Foa, E B; McNally, R; Murdock, T B

    1989-01-01

    Influenced by Bower (Am. Psychol. 36, 129-148, 1981) and Lang (Anxiety and the Anxiety Disorders, Erlbaum, Hillsdale, N.J., 1985), we tested three hypotheses concerning anxious mood and memory: (1) the mood state dependent hypothesis which states that memory retrieval will be greater when mood at encoding and at recall are the same than when they are different: (2) the encoding mood congruent hypothesis which states that information semantically related to mood at encoding is retrieved more readily than information unrelated to mood at encoding; and (3) the recall mood congruent hypothesis which states that information semantically related to mood at recall is retrieved more readily than information unrelated to mood at recall. We induced anxiety in speech anxious students by informing them that they would be delivering a speech during the experiment. Mood could be either anxious or nonanxious at encoding, recall, both, or neither. Hence, there were four groups: Anxiety-Anxiety, Anxiety-Nonanxiety, Nonanxiety-Anxiety, and Nonanxiety-Nonanxiety. Subjects were asked to rate the self-descriptiveness of anxiety (e.g. NERVOUS) and nonanxiety adjective (e.g. POLITE) during the encoding phase, and to recall them later. Anxious mood was measured by self-report scales and by heart rate. No support was obtained for any of the three hypotheses. However, post-hoc analyses indicated that anxiety words were recalled least often in subjects whose heart rate increased from encoding to recall. This suggests that attention to threat information may diminish in aroused nonclinical subjects.

  8. Central HIV-1 Tat exposure elevates anxiety and fear conditioned responses of male mice concurrent with altered mu-opioid receptor-mediated G-protein activation and β-arrestin 2 activity in the forebrain.

    PubMed

    Hahn, Yun K; Paris, Jason J; Lichtman, Aron H; Hauser, Kurt F; Sim-Selley, Laura J; Selley, Dana E; Knapp, Pamela E

    2016-08-01

    Co-exposure to opiates and HIV/HIV proteins results in enhanced CNS morphological and behavioral deficits in HIV(+) individuals and in animal models. Opiates with abuse liability, such as heroin and morphine, bind preferentially to and have pharmacological actions through μ-opioid-receptors (MORs). The mechanisms underlying opiate-HIV interactions are not understood. Exposure to the HIV-1 transactivator of transcription (Tat) protein causes neurodegenerative outcomes that parallel many aspects of the human disease. We have also observed that in vivo exposure to Tat results in apparent changes in morphine efficacy, and thus have hypothesized that HIV proteins might alter MOR activation. To test our hypothesis, MOR-mediated G-protein activation was determined in neuroAIDS-relevant forebrain regions of transgenic mice with inducible CNS expression of HIV-1 Tat. G-protein activation was assessed by MOR agonist-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate ([(35)S]GTPγS) autoradiography in brain sections, and in concentration-effect curves of MOR agonist-stimulated [(35)S]GTPγS binding in membranes isolated from specific brain regions. Comparative studies were done using the MOR-selective agonist DAMGO ([D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin) and a more clinically relevant agonist, morphine. Tat exposure reduced MOR-mediated G-protein activation in an agonist, time, and regionally dependent manner. Levels of the GPCR regulatory protein β-arrestin-2, which is involved in MOR desensitization, were found to be elevated in only one affected brain region, the amygdala; amygdalar β-arrestin-2 also showed a significantly increased association with MOR by co-immunoprecipitation, suggesting decreased availability of MOR. Interestingly, this correlated with changes in anxiety and fear-conditioned extinction, behaviors that have substantial amygdalar input. We propose that HIV-1 Tat alters the intrinsic capacity of MOR to signal in response to agonist binding

  9. BEHAVIORAL AND MEMORY CHANGES IN Mus musculus COINFECTED BY Toxocara canis AND Toxoplasma gondii

    PubMed Central

    Corrêa, Flávia Motta; Chieffi, Pedro Paulo; Lescano, Susana A. Zevallos; dos Santos, Sergio Vieira

    2014-01-01

    Several researchers have stated that parasites can alter the behavior of their hosts, in order to increase the transmission rate, principally when prey-predator relationships are a reliable way of infection transmission. The aim of this study was to verify the occurrence of changes in anxiety and short-term memory patterns in experimentally infected Mus musculus by Toxocara canis and/or Toxoplasma gondii. Forty male Mus musculus (Balb/c) eight-week-old were divided into four groups of 10 mice each. One group was infected with 300 eggs of Toxocara canis; a second group was submitted to infection with 10 cysts of Toxoplasma gondii; a third group was concomitantly infected with both parasites with the same inoculums and the last group was maintained without infection. The anxiety levels were evaluated using an elevated plus maze and an actometer; the short-term memory was determined by a two-way active avoidance equipment. The determination of anxiety levels were conducted 40 and 70 days after infection and the short-term memory was evaluated 140 days after infection. Mice chronically infected by Toxoplasma gondii showed impaired learning and short-term memory, but no significant differences were found in mice infected by Toxocara canis or concomitantly infected by Toxocara canis and Toxoplasma gondii when compared to non infected mice. PMID:25076438

  10. Removal of S6K1 and S6K2 Leads to Divergent Alterations in Learning, Memory, and Synaptic Plasticity

    ERIC Educational Resources Information Center

    Antion, Marcia D.; Merhav, Maayan; Hoeffer, Charles A.; Reis, Gerald; Kozma, Sara C.; Thomas, George; Schuman Erin M.; Rosenblum, Kobi; Klann, Eric

    2008-01-01

    Protein synthesis is required for the expression of enduring memories and long-lasting synaptic plasticity. During cellular proliferation and growth, S6 kinases (S6Ks) are activated and coordinate the synthesis of de novo proteins. We hypothesized that protein synthesis mediated by S6Ks is critical for the manifestation of learning, memory, and…

  11. Alterations in cognitive and psychological functioning after organic solvent exposure

    SciTech Connect

    Morrow, L.A.; Ryan, C.M.; Hodgson, M.J.; Robin, N. )

    1990-05-01

    Exposure to organic solvents has been linked repeatedly to alterations in both personality and cognitive functioning. To assess the nature and extent of these changes more thoroughly, 32 workers with a history of exposure to mixtures of organic solvents and 32 age- and education-matched blue-collar workers with no history of exposure were assessed with a comprehensive battery of neuropsychological tests. Although both groups were comparable on measures of general intelligence, significant differences were found in virtually all other cognitive domains tested (Learning and Memory, Visuospatial, Attention and Mental Flexibility, Psychomotor Speed). In addition, Minnesota Multiphasic Personality Inventories of exposed workers indicated clinically significant levels of depression, anxiety, somatic concerns and disturbances in thinking. The reported psychological distress was unrelated to degree of cognitive deficit. Finally, several exposure-related variables were associated with poorer performance on tests of memory and visuospatial ability.

  12. Neuropsychological function and memory suppression in conversion disorder.

    PubMed

    Brown, Laura B; Nicholson, Timothy R; Aybek, Selma; Kanaan, Richard A; David, Anthony S

    2014-09-01

    Conversion disorder (CD) is a condition where neurological symptoms, such as weakness or sensory disturbance, are unexplained by neurological disease and are presumed to be of psychological origin. Contemporary theories of the disorder generally propose dysfunctional frontal control of the motor or sensory systems. Classical (Freudian) psychodynamic theory holds that the memory of stressful life events is repressed. Little is known about the frontal (executive) function of these patients, or indeed their general neuropsychological profile, and psychodynamic theories have been largely untested. This study aimed to investigate neuropsychological functioning in patients with CD, focusing on executive and memory function. A directed forgetting task (DFT) using words with variable emotional valence was also used to investigate memory suppression. 21 patients and 36 healthy controls completed a battery of neuropsychological tests and patients had deficits in executive function and auditory-verbal (but not autobiographical) memory. The executive deficits were largely driven by differences in IQ, anxiety and mood between the groups. A subgroup of 11 patients and 28 controls completed the DFT and whilst patients recalled fewer words overall than controls, there were no significant effects of directed forgetting or valence. This study provides some limited support for deficits in executive, and to a lesser degree, memory function in patients with CD, but did not find evidence of altered memory suppression to support the psychodynamic theory of repression.

  13. Electrically-alterable read-only-memory using Si-rich SiO2 injectors and a floating polycrystalline silicon storage layer

    NASA Astrophysics Data System (ADS)

    DiMaria, D. J.; DeMeyer, K. M.; Serrano, C. M.; Dong, D. W.

    1981-07-01

    Currently, electrically-alterable read-only-memory (EAROM) has become increasingly important for memory and logic operations. A novel EAROM device in a field-effect transistor (FET) configuration, which uses a floating polycrystalline silicon (poly-Si) layer on top of thermal SiO2 and a dual electron injector structure (DEIS) between this floating poly-Si and a control gate poly-Si contact, is described. The DEIS stack consists of sequentially chemically vapor deposited (CVD) layers of Si-rich SiO2 (46% atomic Si), SiO2, and Si-rich SiO2 (46% atomic Si) between the poly-Si layers. Electrons from either poly-Si layer can move to the other poly-Si layer biased at the higher voltage with moderate applied voltages. Thus, the floating poly-Si storage layer can be charged with electrons (''write'' operation) or with positive charge (''erase'' operation) in milliseconds with negative and positive control gate voltages, respectively. The average electric fields in the intervening CVD SiO2 layer during writing and erasing are 5-6 MV /cm and 4-5 MV/cm, respectively, and voltages from ±10 V to ±40 V can be used depending on the device configuration. The enhanced electron injection in these devices is believed to be controlled by localized electric field distortion at the Si-rich SiO2-SiO2 interface caused by the two phase (Si and SiO2) nature of the Si-rich SiO2. The electrical asymmetry of the DEIS is believed to be due to differences in the interfaces of the bottom and top Si-rich SiO2 injectors with the intervening SiO2 layer. At the low voltages used for the ''read'' operation in which the charge state of the floating poly-Si layer is sensed by the FET drain current, no read perturb effects are observed. These structures also show excellent charge retention at low voltages, characteristic of a floating poly-Si storage layer surrounded by SiO2. This excellent retention is due to a characteristic of the Si-rich SiO2 in which it builds up a reversible space-charge layer

  14. Evaluation of standardized Bacopa monniera extract in sodium fluoride-induced behavioural, biochemical, and histopathological alterations in mice.

    PubMed

    Balaji, Bhaskar; Kumar, Ekambaram Prem; Kumar, Anil

    2015-01-01

    Effect of standardized Bacopa monniera (BM; family: Scrophulariaceae) extract (100 and 300 mg/kg) against sodium fluoride (NaF; 100 and 200 ppm)-induced behavioural, biochemical, and neuropathological alterations in mice was evaluated. Akinesia, rotarod (motor coordination), forced swim test (depression), open field test (anxiety), transfer latency (memory), cholinesterase (ChE), and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) were determined in mice treated with NaF for 30 days alone and in combination with BM. NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice. However, NaF did not alter the weight gain, feed/water consumption, and anxiety profile. Suppression of ChE levels and increased oxidative stress were observed in mice treated with NaF. Coadministration of BM significantly improved the memory, ChE levels, and antioxidant enzymes but failed to alter the fluoride levels in NaF-treated mice. Histopathological studies revealed that BM protected the neuropathological alterations induced by NaF.

  15. Impaired long-term memory retention: common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice.

    PubMed

    Ben Abdallah, Nada M-B; Filipkowski, Robert K; Pruschy, Martin; Jaholkowski, Piotr; Winkler, Juergen; Kaczmarek, Leszek; Lipp, Hans-Peter

    2013-09-01

    In adult rodents, decreasing hippocampal neurogenesis experimentally using different approaches often impairs performance in hippocampus-dependent processes. Nonetheless, functional relevance of adult neurogenesis is far from being unraveled, and deficits so far described in animal models often lack reproducibility. One hypothesis is that such differences might be the consequence of the extent of the methodological specificity used to alter neurogenesis rather than the extent to which adult neurogenesis is altered. To address this, we focused on cranial irradiation, the most widely used technique to impair hippocampal neurogenesis and consequentially induce hippocampus-dependent behavioral deficits. To investigate the specificity of the technique, we thus exposed 4-5 months old female cyclin D2 knockout mice, a model lacking physiological levels of olfactory and hippocampal neurogenesis, to an X-ray dose of 10 Gy, reported to specifically affect transiently amplifying precursors. After a recovery period of 1.5 months, behavioral tests were performed and probed for locomotor activity, habituation, anxiety, and spatial learning and memory. Spatial learning in the Morris water maze was intact in all experimental groups. Although spatial memory retention assessed 24h following acquisition was also intact in all mice, irradiated wild type and cyclin D2 knockout mice displayed memory deficits one week after acquisition. In addition, we observed significant differences in tests addressing anxiety and locomotor activity dependent on the technique used to alter neurogenesis. Whereas irradiated mice were hyperactive regardless of their genotype, cyclin D2 knockout mice were hypoactive in most of the tests and displayed altered habituation. The present study emphasizes that different approaches aimed at decreasing adult hippocampal neurogenesis may result in distinct behavioral impairments related to locomotion and anxiety. In contrast, spatial long-term memory retention is

  16. Add neurons, subtract anxiety

    PubMed Central

    Kheirbek, Mazen A.; Hen, René

    2014-01-01

    IN BRIEF To keep memories from becoming jumbled, the brain must encode the distinct features of events and situations in a way that allows them to be distinguished from one another—a process called pattern separation. Pattern separation enables us to distinguish dangerous situations from similar ones that pose no risk. People with defects in this ability may be prone to anxiety disorders. The process occurs in one of the two regions of the brain that generate neurons throughout life. These fledgling cells seem to be critical to pattern separation. Interventions that specifically boost the ranks of rookie neurons could provide new ways to regulate mood and possibly treat conditions such as post-traumatic stress disorder. PMID:24974712

  17. Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels

    PubMed Central

    Jeon, Seong Gak; Kim, Kyoung Ah; Chung, Hyunju; Choi, Junghyun; Song, Eun Ji; Han, Seung-Yun; Oh, Myung Sook; Park, Jong Hwan; Kim, Jin-il; Moon, Minho

    2016-01-01

    Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic. PMID:27432189

  18. Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels.

    PubMed

    Jeon, Seong Gak; Kim, Kyoung Ah; Chung, Hyunju; Choi, Junghyun; Song, Eun Ji; Han, Seung-Yun; Oh, Myung Sook; Park, Jong Hwan; Kim, Jin-Il; Moon, Minho

    2016-08-31

    Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic. PMID:27432189

  19. Cox-2 Plays a Vital Role in the Impaired Anxiety Like Behavior in Colchicine Induced Rat Model of Alzheimer Disease

    PubMed Central

    Sil, Susmita; Ghosh, Tusharkanti

    2016-01-01

    The anxiety status is changed along with memory impairments in intracerebroventricular colchicine injected rat model of Alzheimer Disease (cAD) due to neurodegeneration, which has been indicated to be mediated by inflammation. Inducible cox-2, involved in inflammation, may have important role in the colchicine induced alteration of anxiety status. Therefore, the present study was designed to investigate the role of cox-2 on the anxiety behavior (response to novelty in an elevated open field space) of cAD by inhibiting it with three different doses (10, 20, and 30 mg) of etoricoxib (a cox-2 blocker) in two time points (14 and 21 days). The results showed anxiolytic behavior in cAD along with lower serum corticosterone level, both of which were recovered at all the doses of etoricoxib on day 21. On day 14 all of the anxiety parameters showed similar results to that of day 21 at high doses but not at 10 mg/kg body weight. Results indicate that the parameters of anxiety were dependent on neuronal circuitries that were probably sensitive to etoricoxib induced blocking of neurodegeneration. The present study showed that anxiolytic behavior in cADr is predominantly due to cox-2 mediated neuroinflammation induced neurodegeneration in the brain. PMID:26880859

  20. The neurodevelopmental basis of math anxiety.

    PubMed

    Young, Christina B; Wu, Sarah S; Menon, Vinod

    2012-05-01

    Math anxiety is a negative emotional reaction to situations involving mathematical problem solving. Math anxiety has a detrimental impact on an individual's long-term professional success, but its neurodevelopmental origins are unknown. In a functional MRI study on 7- to 9-year-old children, we showed that math anxiety was associated with hyperactivity in right amygdala regions that are important for processing negative emotions. In addition, we found that math anxiety was associated with reduced activity in posterior parietal and dorsolateral prefrontal cortex regions involved in mathematical reasoning. Multivariate classification analysis revealed distinct multivoxel activity patterns, which were independent of overall activation levels in the right amygdala. Furthermore, effective connectivity between the amygdala and ventromedial prefrontal cortex regions that regulate negative emotions was elevated in children with math anxiety. These effects were specific to math anxiety and unrelated to general anxiety, intelligence, working memory, or reading ability. Our study identified the neural correlates of math anxiety for the first time, and our findings have significant implications for its early identification and treatment.

  1. Retrospective and Prospective Cognitions in Adolescents: Anxiety, Depression, and Positive and Negative Affect

    ERIC Educational Resources Information Center

    Miles, Helen; MacLeod, Andrew K.; Pote, Helen

    2004-01-01

    Research with anxious and depressed adults has suggested that anxiety is related to an increased anticipation of both negative memories and negative expectancies whereas depression is related to a reduction in positive memories and expectancies. The present study examined whether anxiety and depression in 123 school-aged adolescents would show the…

  2. Cognitive Load Theory: An Empirical Study of Anxiety and Task Performance in Language Learning

    ERIC Educational Resources Information Center

    Chen, I-Jung; Chang, Chi-Cheng

    2009-01-01

    Introduction: This study explores the relationship among three variables--cognitive load, foreign language anxiety, and task performance. Cognitive load refers to the load imposed on working memory while performing a particular task. The authors hypothesized that anxiety consumes the resources of working memory, leaving less capacity for cognitive…

  3. Generalized Anxiety Disorder

    MedlinePlus

    MENU Return to Web version Generalized Anxiety Disorder Overview What is anxiety? Anxiety is a word that describes feelings of worry, nervousness, fear, apprehension, concern or restlessness. Normal feelings ...

  4. Separation Anxiety (For Parents)

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Separation Anxiety KidsHealth > For Parents > Separation Anxiety Print A A ... both of you get through it. How Separation Anxiety Develops Babies adapt pretty well to other caregivers. ...

  5. Social anxiety disorder

    MedlinePlus

    Phobia - social; Anxiety disorder - social; Social phobia; SAD - social anxiety disorder ... People with social anxiety disorder fear and avoid situations in which they may be judged by others. It may begin in the ...

  6. Stop Performance Anxiety!

    ERIC Educational Resources Information Center

    Ely, Mark C.

    1991-01-01

    Discusses how teachers can help music students overcome performance anxiety. Divides performance anxiety into four major components: physiological, cognitive, behavioral, and psychological. Suggests fighting anxiety with relaxation techniques, imagery, cognitive statements, positive thinking, practice, and preparation. Discourages use of…

  7. A quasi-experimental study of a reminiscence program focused on autobiographical memory in institutionalized older adults with cognitive impairment.

    PubMed

    Lopes, Teresa Silveira; Afonso, Rosa Marina Lopes Brás Martins; Ribeiro, Óscar Manuel

    2016-01-01

    Working with past memories through reminiscence interventions has been practiced for several decades with successful outcomes on mental health in older adults. Few studies however have focused on autobiographical memory recall in older individuals with cognitive impairment. This study aims to analyze the impact of an individual reminiscence program in a group of older persons with cognitive decline living in nursing homes on the dimensions of cognition, autobiographical memory, mood, behavior and anxiety. A two-group pre-test and post-test design with single blinded assessment was conducted. Forty-one participants were randomized to an experimental group (n=20) and a control group (n=21). The first group attended five weekly individual reminiscence sessions. Changes in the outcome measures were examined for cognition (Montreal Cognitive Assessment; Autobiographical Memory Test), behavior (Alzheimer Disease Assessment Subscale Non-Cog) and emotional status (Cornell Scale for Depression in Dementia; Geriatric Depression Scale, and Geriatric Anxiety Inventory). Participants attending reminiscence sessions exhibited better outcomes compared to the control group in cognition, anxiety and depression (p<0.001), and presented a higher number of retrieved autobiographical events, specificity of evoked memories and positive valence of events (p<0.001), and also presented lower latency time for recalling events, and lower negative recalled events (p<0.01). This study supports the potential value of reminiscence therapy in improving the recall of autobiographical memory. Reminiscence therapy can be helpful to maintain or improve cognitive function, decrease anxiety and manage depressive symptoms and altered behavior, but further investigation is needed to clarify long-term effects. PMID:27347792

  8. Anxiety Disorders: Support Groups

    MedlinePlus

    ... Anxiety Disorder Treating Anxiety Disorders: Educational Videos Clinical Practice Review for Major Depressive Disorder Meetings & Events Mental Health Apps Announcements Awards Alies Muskin Career Development ...

  9. Effects of multiparity on recognition memory, monoaminergic neurotransmitters, and brain-derived neurotrophic factor (BDNF).

    PubMed

    Macbeth, Abbe H; Scharfman, Helen E; Maclusky, Neil J; Gautreaux, Claris; Luine, Victoria N

    2008-06-01

    Recognition memory and anxiety were examined in nulliparous (NP: 0 litters) and multiparous (MP: 5-6 litters) middle-aged female rats (12 months old) to assess possible enduring effects of multiparity at least 3 months after the last litter was weaned. MP females performed significantly better than NP females on the non-spatial memory task, object recognition, and the spatial memory task, object placement. Anxiety as measured on the elevated plus maze did not differ between groups. Monoaminergic activity and levels were measured in prefrontal cortex, CA1 hippocampus, CA3 hippocampus, and olfactory bulb (OB). NP and MP females differed in monoamine concentrations in the OB only, with MP females having significantly greater concentrations of dopamine and metabolite DOPAC, norepinephrine and metabolite MHPG, and the serotonin metabolite 5-HIAA, as compared to NP females. These results indicate a long-term change in OB neurochemistry as a result of multiparity. Brain-derived neurotrophic factor (BDNF) was also measured in hippocampus (CA1, CA3, dentate gyrus) and septum. MP females had higher BDNF levels in both CA1 and septum; as these regions are implicated in memory performance, elevated BDNF may underlie the observed memory task differences. Thus, MP females (experiencing multiple bouts of pregnancy, birth, and pup rearing during the first year of life) displayed enhanced memory task performance but equal anxiety responses, as compared to NP females. These results are consistent with previous studies showing long-term changes in behavioral function in MP, as compared to NP, rats and suggest that alterations in monoamines and a neurotrophin, BDNF, may contribute to the observed behavioral changes.

  10. Efficacy of meditation in generalized anxiety disorder.

    PubMed

    Vahia, V N; Shetty, H K; Motiwala, S; Thakkar, G; Fernandes, L; Sharma, J C

    1993-04-01

    A study was conducted to compare the efficacy of meditation with that of imipramine and chlordiazepoxide in the treatment of Generalized Anxiety Disorder. At the end of five weeks, meditation was found to be as effective as pharmacotherapy in controlling symptoms of anxiety. It was superior in altering trait anxiety (TMAS Scores). Meditation is an easy to learn and cost effective therapy. It has a distinct edge over pharmacotherapy in that it is does not have the associated problems of habit formation,-withdrawal effects, overdosage or other undesirable effects.

  11. EFFICACY OF MEDITATION IN GENERALIZED ANXIETY DISORDER

    PubMed Central

    Vahia, Vihang N.; Shetty, Harish K.; Motiwala, Shakera; Thakkar, Gira; Fernandes, Lizabeth; Sharma, Jagdish Chandra

    1993-01-01

    A study was conducted to compare the efficacy of meditation with that of imipramine and chlordiazepoxide in the treatment of Generalized Anxiety Disorder. At the end of five weeks, meditation was found to be as effective as pharmacotherapy in controlling symptoms of anxiety. It was superior in altering trait anxiety (TMAS Scores). Meditation is an easy to learn and cost effective therapy. It has a distinct edge over pharmacotherapy in that it is does not have the associated problems of habit formation,-withdrawal effects, overdosage or other undesirable effects. PMID:21743608

  12. Behavioral alterations following blood-brain barrier disruption stimulated by focused ultrasound

    PubMed Central

    Yang, Feng-Yi; Huang, Sheng-Fang; Cheng, Irene Han-Juo

    2016-01-01

    The purpose of this study was to investigate the behavioral alterations and histological changes of the brain after FUS-induced BBB disruption (BBBD). Rats were behaviorally tested using the open field, hole-board, and grip strength tests from day 1 through day 32 after undergoing BBBD induced by FUS with either a mild or heavy parameter. In the open field test, we found an increase in center entries on day 1 and day 9 following heavy FUS treatment and a decrease in center entries at day 18 following mild FUS treatment. With regard to memory-related alterations, rats subjected to heavy FUS treatment exhibited longer latency to start exploring and to find the first baited hole. However, rats subjected to mild FUS treatment exhibited no significant differences in terms of memory performance or grip force. The obtained data suggest that heavy FUS treatment might induce hyperactivity, spatial memory impairment, and forelimb gripping deficits. Furthermore, while mild FUS treatment may have an impact on anxiety-related behaviors, the data suggested it had no impact on locomotor activity, memory, or grip force. Thus, the behavioral alterations following FUS-induced BBBD require further investigation before clinical application. PMID:27034007

  13. The Timing of Multiple Retrieval Events Can Alter GluR1 Phosphorylation and the Requirement for Protein Synthesis in Fear Memory Reconsolidation

    ERIC Educational Resources Information Center

    Jarome, Timothy J.; Kwapis, Janine L.; Werner, Craig T.; Parsons, Ryan G.; Gafford, Georgette M.; Helmstetter, Fred J.

    2012-01-01

    Numerous studies have indicated that maintaining a fear memory after retrieval requires de novo protein synthesis. However, no study to date has examined how the temporal dynamics of repeated retrieval events affect this protein synthesis requirement. The present study varied the timing of a second retrieval of an established auditory fear memory…

  14. The Influence of Cognition, Anxiety and Psychiatric Disorders over Treatment Adherence in Uncontrolled Hypertensive Patients

    PubMed Central

    Jacobs, Úrsula; De Castro, Mauro S.; Fuchs, Flávio D.; Ferreira, Maria Beatriz C.

    2011-01-01

    Background Poor adherence is estimated to cause 125 thousand deaths per year and is linked to 10% of all hospital stays in the U.S. Up to one third of elderly hypertensive patients don't have adherence, which is responsible for high proportion of hospitalizations. Hypertension is also related to poor performance in tests that assess cognitive functions. On the other hand, poor cognitive performance is associated with low adherence to treatment. Objective To assess the association between cognitive function, anxiety and psychiatric disorders with adherence to drug treatment in patients with hypertension. Methodology and Principal Findings This a cohort studies with 56 adult patients with uncontrolled hypertension who participated of all meetings of a pharmaceutical intervention in a randomized clinical trial of pharmaceutical care. Cognitive function was measured by the Mini Mental State Examination (Mini-mental). The memory was measured by digit and word spans, tower and church shadow test, short story test and metamemory. Anxiety and psychiatric disorders were evaluated by the State Trace Anxiety Inventory and the Self-Report Questionnaire, respectively. The participants were classified as adherent or non-adherent to the drug treatment, according to the identification of plasma levels of hydrochlorothiazide. All non-adherent patients (n = 12) and 35 out 44 (79.5%) patients with adherence to treatment had at least one memory test with an altered score (P = 0.180). Participants with an unsatisfactory score in the Mini-mental had six-fold higher risk of non-adherence to treatment when compared to those with a normal score (RR = 5.8; CI 95%: 1.6–20.8; P = 0.007). The scores of anxiety and psychiatric disorders were not associated with adherence to the pharmacological treatment. Conclusion Cognitive deficit impairs adherence to drug therapy and should be screened as part of a program of pharmaceutical care to improve adherence to treatment. PMID

  15. Memory and mood during MDMA intoxication, with and without memantine pretreatment.

    PubMed

    de Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Heckman, P; de la Torre, R; Farre, M; Ramaekers, J G

    2014-12-01

    Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning Task. Profile of Mood State and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigour, arousal, elation) and negative mood effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans. This article is part of the Special Issue entitled 'CNS Stimulants'.

  16. Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion.

    PubMed

    Vallée, M; Mayo, W; Dellu, F; Le Moal, M; Simon, H; Maccari, S

    1997-04-01

    It is well known that the hypothalamo-pituitary-adrenal (HPA) axis is altered by early environmental experiences, particularly in the perinatal period. This may be one mechanism by which the environment changes the physiology of the animal such that individual differences in adult adaptative capabilities, such as behavioral reactivity and memory performance, are observable. To determine the origin of these behavioral individual differences, we have investigated whether the long-term influence of prenatal and postnatal experiences on emotional and cognitive behaviors in adult rats are correlated with changes in HPA activity. To this end, prenatal stress of rat dams during the last week of gestation and postnatal daily handling of rat pups during the first 3 weeks of life were used as two environmental manipulations. The behavioral reactivity of the adult offspring in response to novelty was evaluated using four different parameters: the number of visits to different arms in a Y-maze, the distance covered in an open field, the time spent in the corners of the open field, and the time spent in the open arms of an elevated plus-maze. Cognitive performance was assessed using a water maze and a two-trial memory test. Adult prenatally stressed rats showed high anxiety-like behavior, expressed as an escape behavior to novelty correlated with high secretion of corticosterone in response to stress, whereas adult handled rats exhibited low anxiety-like behavior, expressed as high exploratory behavior correlated with low secretion of corticosterone in response to stress. On the other hand, neither prenatal stress nor handling changed spatial learning or memory performance. Taken together, these results suggest that individual differences in adult emotional status may be governed by early environmental factors; however, perinatal experiences are not effective in influencing adult memory capacity.

  17. Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion.

    PubMed

    Vallée, M; Mayo, W; Dellu, F; Le Moal, M; Simon, H; Maccari, S

    1997-04-01

    It is well known that the hypothalamo-pituitary-adrenal (HPA) axis is altered by early environmental experiences, particularly in the perinatal period. This may be one mechanism by which the environment changes the physiology of the animal such that individual differences in adult adaptative capabilities, such as behavioral reactivity and memory performance, are observable. To determine the origin of these behavioral individual differences, we have investigated whether the long-term influence of prenatal and postnatal experiences on emotional and cognitive behaviors in adult rats are correlated with changes in HPA activity. To this end, prenatal stress of rat dams during the last week of gestation and postnatal daily handling of rat pups during the first 3 weeks of life were used as two environmental manipulations. The behavioral reactivity of the adult offspring in response to novelty was evaluated using four different parameters: the number of visits to different arms in a Y-maze, the distance covered in an open field, the time spent in the corners of the open field, and the time spent in the open arms of an elevated plus-maze. Cognitive performance was assessed using a water maze and a two-trial memory test. Adult prenatally stressed rats showed high anxiety-like behavior, expressed as an escape behavior to novelty correlated with high secretion of corticosterone in response to stress, whereas adult handled rats exhibited low anxiety-like behavior, expressed as high exploratory behavior correlated with low secretion of corticosterone in response to stress. On the other hand, neither prenatal stress nor handling changed spatial learning or memory performance. Taken together, these results suggest that individual differences in adult emotional status may be governed by early environmental factors; however, perinatal experiences are not effective in influencing adult memory capacity. PMID:9065522

  18. Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior

    PubMed Central

    Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B.; Singewald, Nicolas; Pollak, Daniela D.

    2016-01-01

    ABSTRACT Introduction Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs – also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. Materials and methods The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). Results The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. Discussion The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed. PMID:26679264

  19. The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry.

    PubMed

    Galani, Rodrigue; Berthel, Marie-Camille; Lazarus, Christine; Majchrzak, Monique; Barbelivien, Alexandra; Kelche, Christian; Cassel, Jean-Christophe

    2007-07-01

    To assess a possible role for serotonin in the mediation of the behavioral changes induced by enriched housing conditions (EC), adult female Long-Evans rats sustaining a serotonin depletion (150 microg of 5,7-dihydroxytryptamine, icv) and sham-operated rats were housed postoperatively for 30 days in enriched (12 rats/large cage containing various objects) or standard housing conditions (2 rats/standard laboratory cage). Thereafter, anxiety responses (elevated plus-maze), locomotor activity (in the home-cage), sensori-motor capabilities (beam-walking task), and spatial memory (eight-arm radial maze) were assessed. Monoamine levels were subsequently measured in the frontoparietal cortex and the hippocampus. Overall, EC reduced anxiety-related responses, enhanced sensori-motor performance and improved the memory span in the initial stage of the spatial memory task. Despite a substantial reduction of serotonergic markers in the hippocampus (82%) and the cortex (74%), these positive effects of EC were not altered by the lesion. EC reduced the serotonin levels in the ventral hippocampus (particularly in unlesioned rats: -23%), increased serotonin turnover in the entire hippocampus (particularly in lesioned rats: +36%) and augmented the norepinephrine levels in the dorsal hippocampus (+68% in unlesioned and +49% in lesioned rats); no such alterations were found in the frontoparietal cortex. Our data suggest that an intact serotonergic system is not a prerequisite for the induction of positive behavioral effects by EC. The neurochemical changes found in the hippocampus of EC rats, however, show that the monoaminergic innervation of the hippocampus is a target of EC. PMID:17493843

  20. A Selective Intervention Program for Inhibited Preschool-Aged Children of Parents with an Anxiety Disorder: Effects on Current Anxiety Disorders and Temperament

    ERIC Educational Resources Information Center

    Kennedy, Susan J.; Rapee, Ronald M.; Edwards, Susan L.

    2009-01-01

    The efficacy of early intervention for preschool-aged children at risk of anxiety disorders is investigated. Brief early intervention delivered through parents can reduce anxiety and associated risk and may alter the developmental trajectory of anxiety in some young children.

  1. A role for LYNX2 in anxiety-related behavior

    PubMed Central

    Tekinay, Ayse B.; Nong, Yi; Miwa, Julie M.; Lieberam, Ivo; Ibanez-Tallon, Ines; Greengard, Paul; Heintz, Nathaniel

    2009-01-01

    Anxiety disorders are the most prevalent mental disorders in developed societies. Although roles for the prefrontal cortex, amygdala, hippocampus and mediodorsal thalamus in anxiety disorders are well documented, molecular mechanisms contributing to the functions of these structures are poorly understood. Here we report that deletion of Lynx2, a mammalian prototoxin gene that is expressed at high levels in anxiety associated brain areas, results in elevated anxiety-like behaviors. We show that LYNX2 can bind to and modulate neuronal nicotinic receptors, and that loss of Lynx2 alters the actions of nicotine on glutamatergic signaling in the prefrontal cortex. Our data identify Lynx2 as an important component of the molecular mechanisms that control anxiety, and suggest that altered glutamatergic signaling in the prefrontal cortex of Lynx2 mutant mice contributes to increased anxiety-related behaviors. PMID:19246390

  2. Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice.

    PubMed

    Painsipp, E; Wultsch, T; Edelsbrunner, M E; Tasan, R O; Singewald, N; Herzog, H; Holzer, P

    2008-07-01

    Neuropeptide Y (NPY) acting through Y1 receptors reduces anxiety- and depression-like behavior in rodents, whereas Y2 receptor stimulation has the opposite effect. This study addressed the implication of Y4 receptors in emotional behavior by comparing female germ line Y4 knockout (Y4-/-) mice with control and germ line Y2-/- animals. Anxiety- and depression-like behavior was assessed with the open field (OF), elevated plus maze (EPM), stress-induced hyperthermia (SIH) and tail suspension tests (TST), respectively. Learning and memory were evaluated with the object recognition test (ORT). In the OF and EPM, both Y4-/- and Y2-/- mice exhibited reduced anxiety-related behavior and enhanced locomotor activity relative to control animals. Locomotor activity in a familiar environment was unchanged in Y4-/- but reduced in Y2-/- mice. The basal rectal temperature exhibited diurnal and genotype-related alterations. Control mice had temperature minima at noon and midnight, whereas Y4-/- and Y2-/- mice displayed only one temperature minimum at noon. The magnitude of SIH was related to time of the day and genotype in a complex manner. In the TST, the duration of immobility was significantly shorter in Y4-/- and Y2-/- mice than in controls. Object memory 6 h after initial exposure to the ORT was impaired in Y2-/- but not in Y4-/- mice, relative to control mice. These results show that genetic deletion of Y4 receptors, like that of Y2 receptors, reduces anxiety-like and depression-related behavior. Unlike Y2 receptor knockout, Y4 receptor knockout does not impair object memory. We propose that Y4 receptors play an important role in the regulation of behavioral homeostasis.

  3. Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory.

    PubMed

    Hartley, Catherine A; McKenna, Morgan C; Salman, Rabia; Holmes, Andrew; Casey, B J; Phelps, Elizabeth A; Glatt, Charles E

    2012-04-01

    Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.

  4. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

    PubMed Central

    Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

    2015-01-01

    The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario. PMID:26676323

  5. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease.

    PubMed

    Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

    2015-12-01

    The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario. PMID:26676323

  6. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning

    PubMed Central

    Johnson, Philip L.; Molosh, Andrei; Fitz, Stephanie D.; Arendt, Dave; Deehan, Gerald A.; Federici, Lauren M.; Bernabe, Cristian; Engleman, Eric A.; Rodd, Zachary A.; Lowry, Christopher A.; Shekhar, Anantha

    2015-01-01

    The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT (a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5 days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ∼40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC. PMID:26476009

  7. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning.

    PubMed

    Johnson, Philip L; Molosh, Andrei; Fitz, Stephanie D; Arendt, Dave; Deehan, Gerald A; Federici, Lauren M; Bernabe, Cristian; Engleman, Eric A; Rodd, Zachary A; Lowry, Christopher A; Shekhar, Anantha

    2015-11-01

    The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ~40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC. PMID:26476009

  8. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning.

    PubMed

    Johnson, Philip L; Molosh, Andrei; Fitz, Stephanie D; Arendt, Dave; Deehan, Gerald A; Federici, Lauren M; Bernabe, Cristian; Engleman, Eric A; Rodd, Zachary A; Lowry, Christopher A; Shekhar, Anantha

    2015-11-01

    The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ~40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

  9. Mechanical memory

    DOEpatents

    Gilkey, Jeffrey C.; Duesterhaus, Michelle A.; Peter, Frank J.; Renn, Rosemarie A.; Baker, Michael S.

    2006-08-15

    A first-in-first-out (FIFO) microelectromechanical memory apparatus (also termed a mechanical memory) is disclosed. The mechanical memory utilizes a plurality of memory cells, with each memory cell having a beam which can be bowed in either of two directions of curvature to indicate two different logic states for that memory cell. The memory cells can be arranged around a wheel which operates as a clocking actuator to serially shift data from one memory cell to the next. The mechanical memory can be formed using conventional surface micromachining, and can be formed as either a nonvolatile memory or as a volatile memory.

  10. Mechanical memory

    DOEpatents

    Gilkey, Jeffrey C.; Duesterhaus, Michelle A.; Peter, Frank J.; Renn, Rosemarie A.; Baker, Michael S.

    2006-05-16

    A first-in-first-out (FIFO) microelectromechanical memory apparatus (also termed a mechanical memory) is disclosed. The mechanical memory utilizes a plurality of memory cells, with each memory cell having a beam which can be bowed in either of two directions of curvature to indicate two different logic states for that memory cell. The memory cells can be arranged around a wheel which operates as a clocking actuator to serially shift data from one memory cell to the next. The mechanical memory can be formed using conventional surface micromachining, and can be formed as either a nonvolatile memory or as a volatile memory.

  11. MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults.

    PubMed

    Wefers, Benedikt; Hitz, Christiane; Hölter, Sabine M; Trümbach, Dietrich; Hansen, Jens; Weber, Peter; Pütz, Benno; Deussing, Jan M; de Angelis, Martin Hrabé; Roenneberg, Till; Zheng, Fang; Alzheimer, Christian; Silva, Alcino; Wurst, Wolfgang; Kühn, Ralf

    2012-01-01

    MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype.Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain. PMID:22529971

  12. Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.

    PubMed

    Leão, Anderson H F F; Medeiros, André M; Apolinário, Gênedy K S; Cabral, Alícia; Ribeiro, Alessandra M; Barbosa, Flávio F; Silva, Regina H

    2016-05-01

    The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 μg, 0.1 μg, and 0.2 μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to

  13. Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients

    PubMed Central

    Brandt, Moritz D; Brandt, Kalina; Werner, Annett; Schönfeld, Robby; Loewenbrück, Kai; Donix, Markus; Schaich, Markus; Bornhäuser, Martin; von Kummer, Rüdiger; Leplow, Bernd; Storch, Alexander

    2015-01-01

    Background Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory. Methods To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy (1H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment. Results CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in 1H-MRS. Conclusion Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that 1H-MRS allows the detection of neurogenesis-associated plasticity in the human brain. PMID:26442754

  14. Genetic risk for Alzheimer’s disease alters the five-year trajectory of semantic memory activation in cognitively intact elders

    PubMed Central

    Rao, Stephen M.; Bonner-Jackson, Aaron; Nielson, Kristy A.; Seidenberg, Michael; Smith, J. Carson; Woodard, John L.; Durgerian, Sally

    2015-01-01

    Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer’s disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N=24) and non-carriers (N=21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the

  15. Neonatal transplantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production.

    PubMed

    Ruiz, P; Nassiri, M; Gregorian, S; Viciana, A L; Streilein, J W

    1996-04-27

    Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult Bl0.S (H2s, H2E-) mice that received (Bl0.S x B10.A)F1 cells at birth and before and following application (and rejection or acceptance) of Bl0.A (H2k/d, H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45hi, PgP-1hi, Mel-14neg) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2Kk+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but

  16. Neonatal transplantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production.

    PubMed

    Ruiz, P; Nassiri, M; Gregorian, S; Viciana, A L; Streilein, J W

    1996-04-27

    Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult Bl0.S (H2s, H2E-) mice that received (Bl0.S x B10.A)F1 cells at birth and before and following application (and rejection or acceptance) of Bl0.A (H2k/d, H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45hi, PgP-1hi, Mel-14neg) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2Kk+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but

  17. Test and Performance Anxiety

    ERIC Educational Resources Information Center

    Huberty, Thomas J.

    2009-01-01

    Anxiety is one of the most basic human emotions and occurs in every person at some time, most often when someone is apprehensive about uncertain outcomes of an event or set of circumstances. Anxiety can serve an adaptive function, however, and is also a marker for typical development. In the school setting, anxiety is experienced often by students…

  18. Anxiety and Test Performance.

    ERIC Educational Resources Information Center

    Hickey, Kevin S.

    Test anxiety is a variable cognitive, affective, or physiological response, or any combination thereof, occurring during evaluative, self-report examinations. Research suggests that the cognitive, affective, and physiological components of test anxiety are interrelated and that these components in addition to global test anxiety, are negatively…

  19. Deconstructing Test Anxiety

    ERIC Educational Resources Information Center

    Putwain, David William

    2008-01-01

    Recent changes to educational policy which have focused attention on the use of high stakes testing as performance and accountability measures have renewed interest in test anxiety both in the UK and the USA. The aim of this paper is to provide a critical examination of the test anxiety construct, and explore the ways in which test anxiety is…

  20. Competitive Anxiety in Sport.

    ERIC Educational Resources Information Center

    Martens, Rainer; And Others

    This book is a comprehensive review of competitive anxiety research that has used the Sport Competition Anxiety Test, or SCAT (a trait scale), and the Competitive State Anxiety Inventory-2 (CSAI-2). The book describes the theoretical basis and development procedures for both scales, including detailed information on reliability and validity. In…

  1. Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project.

    PubMed

    Lovallo, William R; Enoch, Mary-Anne; Acheson, Ashley; Cohoon, Andrew J; Sorocco, Kristen H; Hodgkinson, Colin A; Vincent, Andrea S; Goldman, David

    2016-06-01

    Exposure to stress during critical periods of development can have adverse effects on adult health behaviors, and genetic vulnerabilities may enhance these stress effects. We carried out an exploratory examination of psychological, physiological, and behavioral characteristics of 252 healthy young adults for the impact of early-life adversity (ELA) in relation to the G-to-A single nucleotide polymorphism (SNP), rs9296158, of the FKBP5 gene. FKBP5 is a molecular cochaperone that contributes to the functional status of the glucocorticoid receptor (GR) and to the quality of corticosteroid signaling. FKBP5 expression is upregulated by cortisol exposure during stressful episodes, with greater upregulation seen in A-allele carriers. As such, FKBP5 expression and GR function may be environmentally sensitive in A-allele carriers and therefore suitable for the study of gene-by-environment (G × E) interactions. Compared with FKBP5, GG homozygotes (N=118), A-allele carriers (N = 132) without psychiatric morbidity had progressively worse performance on the Stroop color-word task with increasing levels of ELA exposure (Genotype × ELA, F=5.14, P=0.007), indicating a G × E interaction on working memory in early adulthood. In addition, heart rate response to mental stress was diminished overall in AA/AG-allele carriers (F=5.15, P=0.024). Diminished working memory and attenuated autonomic responses to stress are both associated with risk for alcoholism and other substance use disorders. The present data suggest that FKBP5 in the GR pathway may be a point of vulnerability to ELA, as seen in this group of non-traumatized young adults. FKBP5 is accordingly a potential target for more extensive studies of the impact of ELA on health and health behaviors in adulthood.

  2. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats.

    PubMed

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I; Romero, Juan I; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando

    2015-01-01

    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA.

  3. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats.

    PubMed

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I; Romero, Juan I; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando

    2015-01-01

    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA. PMID:26578900

  4. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats

    PubMed Central

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I.; Romero, Juan I.; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J.; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando

    2015-01-01

    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA. PMID:26578900

  5. The frequency of spontaneous seizures in rats correlates with alterations in sensorimotor gating, spatial working memory, and parvalbumin expression throughout limbic regions.

    PubMed

    Wolf, D C; Bueno-Júnior, L S; Lopes-Aguiar, C; Do Val Da Silva, R A; Kandratavicius, L; Leite, J P

    2016-01-15

    Cognitive deficits and psychotic symptoms are highly prevalent in patients with temporal lobe epilepsy (TLE). Imaging studies in humans have suggested that these comorbidities are associated with atrophy in temporal lobe structures and other limbic regions. It remains to be clarified whether TLE comorbidities are due to the frequency of spontaneous seizures or to limbic structural damage per se. Here, we used the pilocarpine model of chronic spontaneous seizures to evaluate the possible association of seizure frequency with sensorimotor gating, spatial working memory, and neuropathology throughout limbic regions. For TLE modeling, we induced a 2-h status epilepticus by the systemic administration of lithium-pilocarpine. Once spontaneous seizures were established, we tested the locomotor activity (open field), spatial working memory (eight-arm radial maze), and sensorimotor gating (prepulse inhibition of acoustic startle). After behavioral testing, the brains were sectioned for hematoxylin-eosin staining (cell density) and parvalbumin immunohistochemistry (GABAergic neuropil) in the prefrontal cortex, nucleus accumbens, thalamus, amygdala, hippocampus, and entorhinal cortex. The animal groups analyzed included chronic epileptic rats, their controls, and rats that received lithium-pilocarpine but eventually failed to express status epilepticus or spontaneous seizures. Epileptic rats showed deficits in sensorimotor gating that negatively correlated with the radial maze performance, and impairments in both behavioral tests correlated with seizure frequency. In addition to neuronal loss at several sites, we found increased parvalbumin immunostaining in the prefrontal cortex (infralimbic area), thalamus (midline and reticular nuclei), amygdala, Ammon's horn, dentate gyrus, and entorhinal cortex. These tissue changes correlated with seizure frequency and impairments in sensorimotor gating. Our work indicates that chronic seizures might impact the inhibitory

  6. Correlation of cerebrovascular disorder and anxiety: The Kecskemet study

    NASA Astrophysics Data System (ADS)

    Sipos, Kornel; Bodo, Michael; Szalay, Piroska; Szucs, Attila

    2010-04-01

    In order to test the hypothesis that anxiety is a risk factor for cardiovascular disease, specifically stroke, we simultaneously measured anxiety and cerebral vascular alternation, using a computer-based system, "Cerberus." Sixty nine psychiatric patients (including an alcoholic subgroup) were selected as subjects for measurements conducted in Kecskemet, Hungary. The five-item short form of anxiety test (STAI) was administered twice during the same session. Between each test, brain pulse waves were recorded by rheoencephalogram (REG). A REG peak time above 180 milliseconds was considered a cerebrovascular alteration (modified after Jenkner). Data were sorted into two groups: low anxiety (N=10) and high anxiety (N=10). Significant differences were found between cardiovascular risk factors (p< 0.001), REG peak time (p<0.043), and heart rate (p< 0.045). Six subjects showed cerebrovascular alteration in the high anxiety group, and two in the low anxiety group. For the two anxiety groups, there were no significant differences in body mass index, cardiovascular sympathetic-parasympathetic balance, age and symptoms of transient ischemic attack. The correlation of REG and age was significantly different only for the alcoholic subgroup (Szalay et al, 2007). These data support the hypothesis that a correlation exists between cerebrovascular disorder and anxiety in the studied population.

  7. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  8. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients. PMID:27235733

  9. Cognitive Function in Parkinson's Disease Patients with and without Anxiety

    PubMed Central

    Walton, C. C.; Lewis, S. J. G.

    2016-01-01

    Research on the implications of anxiety in Parkinson's disease (PD) has been neglected despite its prevalence in nearly 50% of patients and its negative impact on quality of life. Previous reports have noted that neuropsychiatric symptoms impair cognitive performance in PD patients; however, to date, no study has directly compared PD patients with and without anxiety to examine the impact of anxiety on cognitive impairments in PD. This study compared cognitive performance across 50 PD participants with and without anxiety (17 PDA+; 33 PDA−), who underwent neurological and neuropsychological assessment. Group performance was compared across the following cognitive domains: simple attention/visuomotor processing speed, executive function (e.g., set-shifting), working memory, language, and memory/new verbal learning. Results showed that PDA+ performed significantly worse on the Digit Span forward and backward test and Part B of the Trail Making Task (TMT-B) compared to the PDA− group. There were no group differences in verbal fluency, logical memory, or TMT-A performance. In conclusion, anxiety in PD has a measurable impact on working memory and attentional set-shifting. PMID:27800180

  10. MicroRNA Regulators of Anxiety and Metabolic Disorders.

    PubMed

    Meydan, Chanan; Shenhar-Tsarfaty, Shani; Soreq, Hermona

    2016-09-01

    Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulatory networks in metabolic and anxiety-related conditions. In particular, miRNAs involved in these disorders include regulators of acetylcholine signaling in the nervous system and their accompanying molecular machinery. These have been associated with anxiety-prone states in individuals, while also acting as inflammatory suppressors. In peripheral tissues, altered miRNA pathways can lead to dysregulated metabolism. Common pathways in metabolic and anxiety-related phenomena might offer an opportunity to reclassify 'healthy' and 'unhealthy', as well as metabolic and anxiety-prone biological states, and inform putative strategies to treat these disorders. PMID:27496210

  11. Hypnosis, memory and amnesia.

    PubMed Central

    Kihlstrom, J F

    1997-01-01

    Hypnotized subjects respond to suggestions from the hypnotist for imaginative experiences involving alterations in perception and memory. Individual differences in hypnotizability are only weakly related to other forms of suggestibility. Neuropsychological speculations about hypnosis focus on the right hemisphere and/or the frontal lobes. Posthypnotic amnesia refers to subjects' difficulty in remembering, after hypnosis, the events and experiences that transpired while they were hypnotized. Posthypnotic amnesia is not an instance of state-dependent memory, but it does seem to involve a disruption of retrieval processes similar to the functional amnesias observed in clinical dissociative disorders. Implicit memory, however, is largely spared, and may underlie subjects' ability to recognize events that they cannot recall. Hypnotic hypermnesia refers to improved memory for past events. However, such improvements are illusory: hypermnesia suggestions increase false recollection, as well as subjects' confidence in both true and false memories. Hypnotic age regression can be subjectively compelling, but does not involve the ablation of adult memory, or the reinstatement of childlike modes of mental functioning, or the revivification of memory. The clinical and forensic use of hypermnesia and age regression to enhance memory in patients, victims and witnesses (e.g. recovered memory therapy for child sexual abuse) should be discouraged. PMID:9415925

  12. Cognitive and somatic anxiety.

    PubMed

    Steptoe, A; Kearsley, N

    1990-01-01

    Three hundred and forty adults (including sports players, recreational exercisers, mediators and sedentary controls) completed three inventories purporting to measure cognitive and somatic aspects of anxiety. These were the Cognitive-Somatic Anxiety Questionnaire (CSAQ) devised by Schwartz, Davidson & Goleman (Psychosomatic Medicine, 40, 321-328, 1978), the Worry-Emotionality Scale (WES, Morris, Davis & Hutchens, Journal of Educational Psychology, 73, 541-555, 1981) and the Lehrer-Woolfolk (1982) Anxiety Symptom Questionnaire (LWASQ). Factor analysis of the CSAQ and WES identified distinct cognitive and somatic anxiety factors in both inventories. Higher somatic than cognitive ratings were recorded on the CSAQ and WES, while the pattern was reversed on the LWASQ. The CSAQ can tentatively be recommended as a useful measure of these two anxiety components. We were unable to confirm an observation made previously in the literature that practice of meditation is associated with reduced cognitive anxiety, or that exercise is linked with lower somatic anxiety.

  13. Anxiety in Huntington's Disease.

    PubMed

    Dale, Maria; van Duijn, Erik

    2015-01-01

    Anxiety is common in Huntington's disease (HD), though it has been under-researched. The authors conducted a systematic review of anxiety in HD. The prevalence of anxiety in manifest HD ranged from 13% to 71%. No significant difference in anxiety between manifest and premanifest HD carriers was revealed. Anxiety appears to be associated with depression, suicide, irritability, quality of life (QoL), pain, illness beliefs, and coping styles but does not seem to be linked with measures of disease progression. From the few pilot studies available, interventions that show promise include olanzapine and psychosocial approaches. Improved assessment, more exploration of the nature of anxiety in HD, and evaluation of anxiety interventions are required. PMID:25803201

  14. In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

    PubMed Central

    Curran, Christine P.; Genter, Mary Beth; Patel, Krishna V.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on

  15. Neuromodulation for restoring memory.

    PubMed

    Bick, Sarah K B; Eskandar, Emad N

    2016-05-01

    Disorders of learning and memory have a large social and economic impact in today's society. Unfortunately, existing medical treatments have shown limited clinical efficacy or potential for modification of the disease course. Deep brain stimulation is a successful treatment for movement disorders and has shown promise in a variety of other diseases including psychiatric disorders. The authors review the potential of neuromodulation for the treatment of disorders of learning and memory. They briefly discuss learning circuitry and its involvement in Alzheimer disease and traumatic brain injury. They then review the literature supporting various targets for neuromodulation to improve memory in animals and humans. Multiple targets including entorhinal cortex, fornix, nucleus basalis of Meynert, basal ganglia, and pedunculopontine nucleus have shown a promising potential for improving dysfunctional memory by mechanisms such as altering firing patterns in neuronal networks underlying memory and increasing synaptic plasticity and neurogenesis. Significant work remains to be done to translate these findings into durable clinical therapies. PMID:27132526

  16. An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders

    PubMed Central

    Donner, Jonas; Pirkola, Sami; Silander, Kaisa; Kananen, Laura; Terwilliger, Joseph D.; Lönnqvist, Jouko; Peltonen, Leena; Hovatta, Iiris

    2008-01-01

    Background Human anxiety disorders are complex diseases with largely unknown etiology. We have taken a cross-species approach to identify genes that regulate anxiety-like behavior with inbred mouse strains that differ in their innate anxiety levels as a model. We previously identified 17 genes with expression levels that correlate with anxiety behavior across the studied strains. In the present study, we tested their 13 known human homologues as candidate genes for human anxiety disorders with a genetic association study. Methods We describe an anxiety disorder study sample derived from a Finnish population-based cohort and consisting of 321 patients and 653 carefully matched control subjects, all interviewed to obtain DSM-IV diagnoses. We genotyped altogether 208 single nucleotide polymorphisms (SNPs) (all non-synonymous SNPs, SNPs that alter potential microRNA binding sites, and gap-filling SNPs selected on the basis of HapMap information) from the investigated anxiety candidate genes. Results Specific alleles and haplotypes of six of the examined genes revealed some evidence for association (p ≤ .01). The most significant evidence for association with different anxiety disorder subtypes were: p = .0009 with ALAD (δ-aminolevulinate dehydratase) in social phobia, p = .009 with DYNLL2 (dynein light chain 2) in generalized anxiety disorder, and p = .004 with PSAP (prosaposin) in panic disorder. Conclusions Our findings suggest that variants in these genes might predispose to specific human anxiety disorders. These results illustrate the potential utility of cross-species approaches in identification of candidate genes for psychiatric disorders. PMID:18639233

  17. Course of symptom change during anxiety treatment: Reductions in anxiety and depression in patients completing the Coordinated Anxiety Learning and Management Program

    PubMed Central

    Bomyea, Jessica; Lang, Ariel; Craske, Michelle G.; Chavira, Denise A.; Sherbourne, Cathy D.; Rose, Raphael D.; Golinelli, Daniela; Campbell-Sills, Laura; Welch, Stacy S.; Sullivan, Greer; Bystritsky, Alexander; Roy-Byrne, Peter; Stein, Murray B.

    2015-01-01

    When treating anxious patients with co-occurring depression, research demonstrates that both types of symptoms independently improve. The current analyses examined how reductions in anxiety and depression may be interrelated both during treatment, as well as over time following treatment. Participants were 503 individuals with one or more DSM-IV anxiety disorders who completed a collaborative care anxiety management program. Anxiety and depression were assessed at each treatment session (i.e., session by session data) and also at 6, 12, and 18-month post-baseline assessments (i.e., long-term outcomes data). Mediation analysis examined changes in symptoms in