The immune response is a complex series of cell-mediated reactions by which an organism combats infection, responds to injury, external stresses, or disease. In both Drosophila melanogaster and vertebrates, aging is associated with progressive declines in physiological functions as well as susceptibility to stress and disease. Naturally, the immune activity is increased with age, yet the efficacy of this response is reduced with age. Conversely, when the immune activation is artificially-induced by Lipopolysaccharide, aging is accelerated. Like aging, neurodegeneration is also associated with increased immune activity. The Blood-Brain barrier (BBB) is a physical barrier with highly selective permeability that isolates the brain from the rest of the body. This barrier is essential for ion homeostasis, and exclusion or efflux of exogenous chemicals. The exclusion properties of the Dm BBB are facilitated by paracellular septate junctions of subperineural glia (SPG), which prevent diffusion into or out of the brain. Using the GAL/UAS system in Drosophila, we found that activation of a glial-specific immune response in either immunodeficiency (IMD) or Toll pathways led to reductions in lifespan and age-dependent negative geotaxis. These reductions were also correlated with an early sensitivity towards oxidative and thermal stresses. Furthermore, we found that a SPG-specific immune response of the Toll pathway or disruption of the paracellular BBB itself was sufficient to show the same reductions as pan-glial activation. In short, we found that flies with CNS-specific immune activation showed an inability to cope with long-term and acute forms of stress, and that SPG-specific Toll Activation was sufficient to show these effects. This implicates chronic immune response as a negative factor during aging, neurodegenerative disease, and brain homeostasis. / Thesis / Master of Science (MSc)

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Background: Persistent stress contributes to the onset and maintenance of problem gambling (PG), increasing risks for physiological disturbances. However, minimal research examines acute stress effects and relationships with PG features such as impulsivity or gambling urges. Purpose: The current study examines multiple facets of acute subjective and physiological stress responses in PG. Stress effects on gambling urges and relationships with impulsivity are also explored. Methods: A PG (n=21) and healthy control (HC; n=21) group were exposed to acute psychosocial stress. Saliva samples were collected while participants completed self-report measures of mood and gambling urges. Gambling urges, salivary cortisol (sC), salivary alpha-amylase (sAA), and subjective stress reactivity and recovery were compared within and between groups from baseline up to an hour following stress. Relationships between trait impulsivity, gambling urges, and all aspects of the acute stress response were examined. Results: The PG group showed blunted sC reactivity but reported heightened mood disturbances compared to HCs, while sAA levels did not differ between groups. Within PG and HC groups, sAA had a more rapid acute stress onset than sC, but between-marker differences were pronounced in PG. Self-reported gambling urges were high among PG participants but remained relatively unchanged following acute stress. Impulsivity was positively associated with gambling urges, however, it was not correlated with the acute stress response. Conclusions: This study provides a novel and wide-ranging assessment of the acute stress response in PG, for which research is currently limited. These results indicate that high stress in PG contributes to multi-faceted alterations of the acute stress response relative to HCs. Self-reported gambling urges are elevated and associated with greater trait impulsivity in PG but are unaffected by acute stress exposure. Our findings provide insight into acute stress processing dysfunction in PG and have implications for potential harms, such as increased suicide risk. / Thesis / Master of Science (MSc) / Chronic or continuous life stress can increase the risk of developing and sustaining gambling problems. The current study assessed the effects of a 20-minute stressful task on mood, physiological reactions, the desire to gamble, and their relationships with impulsivity in healthy individuals compared to those with problem gambling (PG). Results showed that after the stressor, the PG group reported more negative mood, but physiological reactions were reduced when compared to healthy participants. In individuals with PG, a greater desire to gamble was correlated with being more impulsive. Overall, our findings show that the long-term stress typically experienced by individuals with PG can affect their mental and physiological reactions to temporary stressors. Additionally, more impulsive individuals show a greater desire to gamble, which may contribute to problematic gambling behaviours. Future research should assess the life impacts of chronic stress in PG, such as the risk of gambling relapse and suicide.

Made available in DSpace on 2014-12-17T15:37:23Z (GMT). No. of bitstreams: 1 VivianeSM.pdf: 285646 bytes, checksum: 806d8cb57146ca69bbc7d647f187939d (MD5) Previous issue date: 2007-05-07 / The stress responses can be parameters used in order to identify the welfare of animals. Behavior parameters can also be regarded as means to identify their relation to stressing situations. In this study, adult male and female poodle dogs, accustomed (group 1) or not (group 2) to the environment of a bath and grooming salon were analyzed through the plasmatic concentration of cortisol, cell counting of the immune system (total leukocytes and percentage of neutrophils and lymphocytes) and through observation of changes in behavior before and after the bath and grooming service. After arriving at the kennel, the dogs were taken to the bath and grooming facility, where they had their blood samples taken and were observed for ten minutes. The subsequent procedures consisted of the bath and grooming services and the collection of another blood samples. The research results were analyzed through non-parametric statistic tests and p < 0.05. Accustomed and non-accustomed dogs presented different hormonal and behavior responses: accustomed dogs presented an increasing of the cortisol level at the second blood samples collection, thus indicating stress towards the aforementioned procedures and presenting behavior responses which can be described as moderated stress. Non-accustomed dogs presented the same cortisol levels in both first and second samples suggesting that they were already reacting to the new environment. Dogs also shown behavioral responses which can be described as acute stress. Both male and female dogs showed similar immunological changes as well as different endocrine and behavioral profiles. Concerning aggression, this study demonstrates that biting the owner can be a predicting behavior of aggression during the bath and grooming service, male dogs were more aggressive than the female, and that males were more reactive to unknown caretaker. The results of this research propose that the familiarization of the animal with the bath and grooming environment and caretaker is important to the welfare of poodle dogs, especially to that of male dogs / As respostas de estresse podem ser vari?veis utilizadas para identificar o n?vel de bem-estar dos animais. Par?metros comportamentais tamb?m podem ser usados tentando identificar sua correspond?ncia com situa??es estressantes. Neste estudo c?es da ra?a poodle, adultos, de ambos os sexos, familiarizados (Grupo 1) e n?o familiarizados (Grupo 2) a um ambiente de sal?o de beleza canino foram avaliados por meio da concentra??o plasm?tica de cortisol, contagem de c?lulas do sistema imune (leuc?citos totais e percentuais de neutr?filos e linf?citos) e observa??o de altera??es comportamentais antes e ap?s os procedimentos de banho e tosa. Ap?s a chegada do animal no canil, dentro do ambiente de banho e tosa, foi realizada uma primeira coleta de sangue seguida por um intervalo de observa??o de 10 minutos, realiza??o dos procedimentos de banho e tosa e coleta de uma segunda amostra de sangue. Os resultados foram analisados usando testes estat?sticos n?o param?tricos e o valor de p < 0.05. C?es familiarizados e n?o familiarizados tiveram respostas hormonais e comportamentais diferentes: os c?es familiarizados apresentaram eleva??o do cortisol na segunda coleta, indicando o estresse provavelmente aos procedimentos, e respostas comportamentais que podem ser caracterizadas como estresse moderado. Os c?es n?o familiarizados ao ambiente apresentaram concentra??es semelhantes de cortisol na primeira e segunda coletas sugerindo que a situa??o estressante parece ser anterior aos procedimentos, provavelmente relacionada ao novo ambiente. Apresentaram tamb?m respostas comportamentais que podem ser caracterizadas como estresse agudo. Machos e f?meas apresentaram altera??es imunol?gicas semelhantes e altera??es end?crinas e comportamentais diferentes entre os sexos nos dois grupos experimentais. Com rela??o ? agressividade observou-se que morder o propriet?rio ? um bom preditor de agressividade durante os procedimentos de banho e tosa, os machos foram mais agressivos que as f?meas e reagiram mais a um tosador estranho. Estes resultados sugerem que a familiaridade do animal ao ambiente de tosa e banho e ao tosador ? importante para o bem-estar animal de c?es da ra?a poodle, particularmente nos machos

This dissertation identifies factors causing the burnout syndrome, which occur especially in the area of work career. It discusses risks that cause the burnout syndrome and the possibilities of its prevention. The theoretical part analyses particular aspects of burnout and describes career as a significant part of human life. The second part of the dissertation evaluates research that was conducted in a chosen organisation. Findings regarding a stress prevention programme are discussed in the second part, as well as the topic of how ready participants are to use the gained knowledge in real life. The paper also assesses how employees and their supervisors evaluate the stress prevention programme. The purpose of this dissertation is to analyse the effectiveness of the stress prevention programme and its impacts. Some suggestions of possible improvements within the programme are also mentioned.

Over 16 million people in the US suffer from major depressive disorder (MDD) each year. Approximately 1/3rd of MDD patients (~5 million) obtain only partial remission or no benefit after trials with multiple drugs or drug combinations. Recently, Ordway and colleagues have reportedelevated levels of DNA oxidation and upregulated gene expression of the base excision repair enzyme poly(ADP-ribose) polymerase-1 (PARP1) in postmortem brain from donors who had MDD at the time of death, as compared to age-matched psychiatrically normal control donors. This study was designed to test whether an inhibitor of PARP, 3-aminobenzamide (3-AB), may be effective to alleviate depressive-like behaviors in a rodent model of treatment-resistant depression. Male rats were ip administered lipopolysaccharide (LPS;100ug/kg) daily for 28 days, and administered a chronic unpredictable stressor on each day. All rats were also administered saline, 3-AB (40 mg/kg), or the serotonin-reuptake inhibitor (SSRI) fluoxetine (trade name: Prozac; 10 mg/kg) on each day, approximately 30 min after LPS treatment. During the 28 day period of LPS treatment, animals were behaviorally tested 5 times on sucrose preference (a test of anhedonia). At the end of the 28 day period, rats were behaviorally tested on a test of acute stress, the Porsolt swim test. Results revealed that 3-AB alleviated anhedonia and the response to acute stress in the Porsolt swim test superior to the fluoxetine group, demonstrating the utility of a PARP inhibitor to alleviate depressive-like behavior in this model. In addition, fluoxetine produced a loss of weight which recovered over days, but not to control levels, and 3-AB did not produce this effect. This study shows that PARP inhibitors may be effective in treatment-resistant depression.

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BACKGROUND AND AIMS: Globally, chronic low back pain (CLBP) affects 70-80% of adults at some point in their lives and current treatments are widely unsuccessful in relieving pain. Understanding the underlying neurophysiological (e.g., descending pain inhibition) and biobehavioral (e.g., stress) processes contributing to chronic pain in patients with CLBP is needed for the development of novel treatments. Previous studies have shown that acute stress can impact pain sensitivity and that childhood trauma may predispose a person to CLBP, but the mechanisms underlying this impact are unknown. Conditioned Pain Modulation (CPM) is a psychophysical paradigm used in research to assess descending pain modulatory pathways, which are thought to be impaired in patients with CLBP as well as in those with childhood trauma. The overlap of conditions has not been explored. The current study explored the impact of childhood trauma on the CPM response within a sample of patients with CLBP being treated at a tertiary pain clinic. CLBP patients exposed to an acute stress paradigm were expected to shower higher pain sensitivity, with acute stress significantly interacting with a history of childhood trauma as a factor leading to the higher pain sensitivity. METHODS: 46 Participants with CLBP (n=46, mean age=49 years, 55.3% female) recruited from a pain treatment service completed a Quantitative Sensory Testing (QST) and CPM before and after an acute psychological stressor. Participants were randomized to a control (n=25) or an acute-stress (n=21) condition. The acute-stress condition included the Stroop Color Word Task (SCWT) and a mental arithmetic task prior to completing the QST protocol a second time. The control participants did not undergo any additional stressors and completed the QST protocol a second time after a 20-minute break. Participants’ CPM response was measured by the average change in pressure pain threshold (PPT) from baseline to the conditioning stimulus (non-dominant hand in ice-water bath). A “Good CPM response” was defined as a CPM effect above 100, indicating that the pain threshold increased when exposed to the conditioning stimulus. To examine the impact of childhood trauma on pain sensitivity, participants completed a Childhood Traumatic Events Scale (CTES) to assess the presence and severity of six types of trauma (death, parental upheaval, sexual, violence, illness or injury, other upheaval) during childhood. The CTES was scored as a continuous variable by calculating the sum the trauma severity for all six trauma types. RESULTS: A large majority of the sample (94% of participants) showed an increase in pain threshold during hand immersion in ice water, which was contrary to our hypothesis based on prior research done on other chronic pain conditions and CLBP. Participants exposed to an acute stressor had an impaired CPM effect compared to those that were not exposed to an acute stressor, however there was no difference between groups (p=0.277). A history of childhood traumatic events did not correlate significantly with an impaired baseline CPM or a change in CPM effect when exposed to an acute stressor. CONCLUSION: The current study used novel QST modalities, including CPM, to analyze the interaction between acute and chronic stress on pain sensitivity. Ultimately, this study found that exposure to an acute stressor had a negative effect on CPM, indicating that when under experimental stress participants were more sensitive to pain compared to when they were not under stress, although the findings were not statistically significant. These findings should be further investigated to expand the understanding of the neurophysiological mechanisms underlying CLBP and to potentially provide novel treatment modalities for patients with CLBP.