Prenatal stress exposure (PNS) has detrimental effects on the offspring’s brain and behaviour and has been identified as an etiological factor in inducing cognitive function deficits in rodents and humans. The neural mechanisms are unclear, however reprogramming of the neuroendocrine stress axis, the hypothalamo-pituitary- adrenal (HPA) axis is hypothesised. A psychosocial stressor (residentintruder paradigm) was used to generate PNS rat offspring, making these studies clinically compatible. The hippocampus and the medial prefrontal cortex (mPFC) are critical in regulating cognitive function and also contribute to the negative feedback control of the HPA axis via corticosteroid receptors, including the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Here the Barnes maze was used to assess spatial learning and memory in male and female PNS offspring during adulthood under different scenarios, including basal and acute and chronic stress conditions. Under basal conditions, PNS was associated with reduced GR and MR mRNA expression in the medial prefrontal cortex (mPFC) and the hippocampus, respectively; suggesting inhibitory feedback control of the HPA axis may be compromised in PNS rats. Moreover, impaired spatial learning was observed in male PNS rats following acute restraint stress. Bilateral lesions of the prelimbic cortex and central administration of an MR antagonist in control rats suggested acute stress-induced learning deficits in PNS males were a result of impaired hippocampus-mediated inhibitory feedback control of the HPA axis. Conversely, a one-week variable stress regimen facilitated spatial learning in PNS rats and this was associated with elevated MR mRNA expression in the dentate gyrus. Moreover, facilitated learning in the PNS rats exposed to chronic stress could be blocked by central administration of an MR antagonist, indicating a facilitatory role of hippocampal MR in spatial learning. In summary, opposite effects of PNS on spatial learning were observed under acute and chronic stress conditions, in which hippocampal MR played a key role in regulating behavioural performance. The effect of age was also examined in PNS rats, and the findings from middle-aged (10-11 months old) rats indicated PNS may accelerate cognitive decline. Sex differences were also studied, with control females’ out-performing males under basal conditions in terms of spatial learning and behavioural flexibility; however following prenatal or chronic stress these sex differences were no longer detected. Furthermore, acute stress impaired spatial learning to a greater extent in females, and this might be attributed to greater HPA axis responses to stress in females compared with males. In conclusion, prenatal stress alters later cognitive performance, in a sex- and stress context-dependent manner. Hippocampal MR plays a critical role in mediating spatial learning, particularly during stress conditions.

A poluição marinha por petróleo e seus derivados é uma preocupação crescente de caráter global. O litoral norte do estado de São Paulo é hoje caracterizado como a região mais altamente impactada por esses contaminantes de toda a costa Sul e Sudeste do país. Dentre as substâncias que compõem esses produtos estão os Hidrocarbonetos Aromáticos Policíclicos (HPAs), como o fenantreno, que apresentam potencial de alterar o sistema endócrino de peixes, gerando desajustes hormonais de alto risco para o processo reprodutivo dos animais expostos. Com base nestes fatos, o presente trabalho buscou verificar efeitos do fenantreno como desregulador endócrino em juvenis de E. marginatus. Essa espécie se caracteriza pelo hermafroditismo protogínico, de modo que os juvenis costumam apresentar altas concentrações de esteroides gonadais, o que gera preocupação quanto os efeitos reprodutivos decorrentes de alterações no padrão de produção de esteroides, especialmente em uma espécie que já vem sofrendo declínios populacionais por conta da sobrepesca. A CL50 encontrada para juvenis de E. marginatus foi 1,51 mg⁄L. Em seguida, foi realizado um bioensaio subletal (96h) com quatro grupos experimentais (n=5) em duplicata: grupo controle; duas concentrações distintas de fenantreno (0,1 mg⁄L e 1 mg⁄L) e grupo exposto ao veículo de diluição (0,004% de etanol). Foram dosadas as concentrações de 17β-estradiol (E2), testosterona (T) e 11-cetotestosterona (11-KT) plasmáticos por ELISA. Gônadas, fígado e baço foram processados para análise histológica. Foi conduzido bioensaio in vitro com incubação de fragmentos gonadais sob ação de fenantreno (50μM) ou etanol. Os níveis dos mesmos esteroides também foram dosados por ELISA. A exposição in vivo ao fenantreno resultou em aumento na área dos hepatócitos, bem como no número de centro melanomacrofágicos e hemossiderose no baço. O etanol induziu efeitos similares no baço. Os níveis de E2 e T não se alteraram no plasma ou no meio de incubação in vitro. O fenantreno reduziu a concentração de 11-KT in vitro e in vivo. No plasma, o etanol também causou esse decréscimo. Considerando a importância do 11-KT no desenvolvimento dos ovários em teleósteos, o fenantreno parece causar desregulação da esteroidogênese em juvenis de E. marginatus, possivelmente gerando disfunções durante a inversão sexual / Marine pollution by crude oil and its residual products is a growing global concern. The Northern coast of São Paulo is characterized as the highly impacted area by these contaminants through Brazil\'s South and Southeast coast. Polycyclic aromatic hydrocarbons (PAH), such as phenanthrene, are the main crude oil components and have a significant toxic potential to biota, acting as endocrine disruptors (ED) and negatively impacting reproduction. This study aimed to investigate the effects of phenanthrene as ED on gonadal steroidogenesis in E. marginatus juveniles. As a hermaphrodite protogynous species, E. marginatus juveniles maintain high levels of plasma steroids as substrates for sex inversion, which causes concern about reproductive effects of disruptions in steroid production patterns, especially in an overfished species. LD50 to E. marginatus exposed to phenanthrene was established in 1.51 mg⁄L. An in vivo sublethal exposure (96 h) to phenanthrene was carried out at two concentrations (0.1mg⁄L and 1 mg⁄L); exposure to the vehicle (ethanol) was also performed. Plasma levels of 17β-estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were measured by ELISA. Gonads, liver and spleen were processed for histological analysis. In an in vitro bioassay, gonad fragments were incubated with phenanthrene (50μM) or ethanol. Steroid levels in the culture media were also measured by ELISA. The in vivo exposure to phenanthrene triggered an increase of the area of the hepatocytes, increased number of melanomacrophagic centers and hemosiderosis in the spleen. Ethanol also induced similar effects on spleen. E2 and T levels did not change neither in plasma nor in vitro media. Phenanthrene sharply reduced 11-KT levels in vitro and in vivo. In plasma, ethanol also decreased 11-KT levels. Considering the importance of 11-KT in fish developing ovaries, phenanthrene seems to disrupt steroidogenesis in juvenile grouper, possibly being able to cause dysfunctions during sex change

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2017-09-11T17:06:11Z No. of bitstreams: 1 LETÍCIA MÜLLER DALLMANN.pdf: 2054002 bytes, checksum: dbb9d492b4d497732fbbd78aa2ebec62 (MD5) / Made available in DSpace on 2017-09-11T17:06:11Z (GMT). No. of bitstreams: 1 LETÍCIA MÜLLER DALLMANN.pdf: 2054002 bytes, checksum: dbb9d492b4d497732fbbd78aa2ebec62 (MD5) Previous issue date: 2016-12-15 / Major depression (MD) is a common, recurrent and incapacitating psychiatric illness, of a multifactorial character whose etiology is still unknown. However, the interaction model between gene and environment, takes into account candidate genes for disease development, response to treatment, and psychosocial factors. As regards the pathogenesis of MD, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role, through the release of corticotropin releasing hormones (CRH), adrenocorticotropic hormones (ACTH), and cortisol. Type 1 receptor in the CRH gene (CRHR1), the receptor for corticotropin releasing hormone (CRH) type 1 (CRHR1), has been associated with depressive and anxious symptoms, as well as response to antidepressant treatment. However, in addition to pharmacological treatment, models of brief psychotherapies have been shown to be effective in response of depressive symptoms and modulation of biological parameters. In this context, the objective of the present project was to investigate the association of the rs110402 SNP in the HPA axis CRHR1 gene with the severity of the depressive and anxious symptoms, as well as the response rates of these symptoms in patients with MD undergoing brief psychotherapy. This study is part of a randomized clinical trial comprised of individuals between 18 and 60 years of age who sought out the UCPel Outpatient Mental Health Research and Extension. At the entrance the individuals were diagnosed through the MINI Plus, they answered a socio-demographic questionnaire, and the biological material was collected. Patients diagnosed with DM were randomized to treatment with cognitive behavioral therapy (CBT) or supportive-expressive dynamic psychotherapy (SEDP), being evaluated in the pre- and post-treatment using the Beck Scale of Depression (BDI-II) scale for severity of depressive symptoms and Beck Anxiety Scale (BAI) for the severity of anxious symptoms. DNA was extracted from peripheral leukocytes and rs110402 polymorphism was genotyped by real-time PCR. Our study showed that genetic variation in the CRHR1 gene is not associated with the severity of depressive and anxious symptoms in patients with MD, however, rs110402 SNP genotypes in the CRHR1 gene may predict the response of psychotherapeutic treatment. Patients with the AA genotype had lower rates of response of the depressive and anxious symptoms in relation to those with the G allele. / A depressão maior (DM) é uma doença psiquiátrica comum, recorrente e incapacitante, de caráter multifatorial cuja etiologia ainda é desconhecida. No entanto, o modelo de interação entre gene e ambiente, leva em consideração genes candidatos para o desenvolvimento da doença, a resposta ao tratamento, e fatores psicossociais. No que se refere a patogênese da DM, a hiperatividade do eixo hipotálamo-pituitária-adrenal (HPA) parece exercer um papel importante, através da liberação dos hormônios liberador de corticotropina (CRH), adrenocorticotropico (ACTH), e cortisol. O receptor tipo 1 para o CRH (CRHR1), tem sido associado aos sintomas depressivos e ansiosos, além da resposta ao tratamento com antidepressivos. Entretanto, além do tratamento farmacológico, modelos de psicoterapias breves têm se demonstrado eficazes na remissão dos sintomas depressivos e modulação de parâmetros biológicos. Neste contexto, o objetivo do presente projeto foi investigar a associação do SNP rs110402 no gene CRHR1 do eixo HPA com a gravidade dos sintomas depressivos e ansiosos, bem como nas taxas de remissão desses sintomas em pacientes com DM submetidos à psicoterapia breve. Este estudo faz parte de um ensaio clínico randomizado composto por indivíduos entre 18 e 60 anos de idade que procuraram o Ambulatório de Pesquisa e Extensão em Saúde Mental da UCPel. Na entrada os indivíduos foram diagnosticados através do MINI Plus, responderam a um questionário sócio demográfico, e foi realizado a coleta de material biológico. Os pacientes com diagnóstico de DM foram randomizados no tratamento com terapia cognitiva comportamental (TCC) ou psicoterapia dinâmica suportiva-expressiva (PDSE), sendo avaliados no pré e pós-tratamento através da escala Escala Beck de Depressão (BDI-II) para severidade de sintomas depressivos e Escala Beck de Ansiedade (BAI) para a severidade de sintomas ansiosos. O DNA foi extraído de leucócitos periféricos e o polimorfismo rs110402 foi genotipado por PCR em tempo real. Nosso estudo mostrou que a variação genética no gene CRHR1 não está associada com a gravidade dos sintomas depressivos e ansiosos em pacientes com DM, no entanto os genótipos do rs110402 SNP no gene CRHR1 podem predizer a resposta do tratamento psicoterapêutico. Pacientes portadores do genótipo AA, apresentaram menores taxas de remissão dos sintomas depressivos e ansiosos em relação àqueles portadores do alelo G.

The “Free Hormone Hypothesis” posits that only free, unbound hormone is biologically active and available to tissues. Conventional biomedical wisdom proposes that corticosteroid-binding globulin (CBG) normally binds 90-95% of blood glucocorticoid (GC), rendering it unavailable to tissues. Under chronic stress, GC levels greatly exceed binding capacity resulting in impaired bodily function and reduced fitness. However, under normal conditions in northern and southern flying squirrels, less than 10% of GC is bound, presenting a major challenge to the hypothesis. To assess the extent of variation in these properties among vertebrates, I compared all species (88) with known GC and CBG and levels. 92% conform reasonably to known convention. Flying squirrels appear as extreme species, as do New World monkeys, yet both groups evolved from ancestors that followed normal convention. I speculate as to how this state evolved and persisted through time.

The “Free Hormone Hypothesis” posits that only free, unbound hormone is biologically active and available to tissues. Conventional biomedical wisdom proposes that corticosteroid-binding globulin (CBG) normally binds 90-95% of blood glucocorticoid (GC), rendering it unavailable to tissues. Under chronic stress, GC levels greatly exceed binding capacity resulting in impaired bodily function and reduced fitness. However, under normal conditions in northern and southern flying squirrels, less than 10% of GC is bound, presenting a major challenge to the hypothesis. To assess the extent of variation in these properties among vertebrates, I compared all species (88) with known GC and CBG and levels. 92% conform reasonably to known convention. Flying squirrels appear as extreme species, as do New World monkeys, yet both groups evolved from ancestors that followed normal convention. I speculate as to how this state evolved and persisted through time.

Following social defeat, male hamsters exhibit behavioral changes characterized by a breakdown of normal territorial aggression and an increase in submissive/defensive behaviors in the presence of a non-aggressive intruder (NAI). We have termed this phenomenon conditioned defeat (CD). By contrast, only a small subset of defeated females exhibit submissive/defensive behavior in the presence of a NAI. We hypothesized that fluctuations in gonadal hormones might contribute to differences in the display of submissive behavior in intact female hamsters. Following social defeat, proestrous females (higher endogenous estradiol) were more likely to display conditioned defeat compared with diestrous 1 (lower endogenous estradiol) females. This finding suggests that there is an estrous cycle-dependent fluctuation in the display of CD in female hamsters and suggests that increased estradiol might contribute to increased submissive behavior. We then demonstrated that ovariectomized females given estradiol prior to CD testing exhibited significantly higher submissive behavior in the presence of a NAI suggesting that estradiol increases the expression of CD in female hamsters. We have also shown that castrated males that were singly housed for four weeks displayed significantly more submissive behavior than did their intact counterparts. Interestingly, castrated and intact males that were singly housed for 10 days prior to behavioral testing displayed similar behavior during CD testing. Together these data suggest that androgens and isolation modulate the display of CD in male hamsters. Finally, we examined brain activation following CD testing in defeated males and females (in diestrus 1 and proestrus). Defeated male and proestrous females exhibited increased Fos activation in the dorsal lateral septum and hypothalamic paraventricular nucleus relative to defeated diestrous 1 females. Diestrous 1 females exhibited increased Fos expression in the lateral bed nucleus of the stria terminalis compared with both defeated groups. Collectively, these data suggest that gonadal hormones and duration of individual housing modulate the display of CD in female and male hamsters and that those animals which display CD exhibit differences in patterns of neuronal activation than do those that do not display CD.

This paper describes two experiments, each of which investigated the impact of stress on human episodic memory. All participants watched narrated slide shows containing emotional and neutral information. Experiment 1 demonstrated that pre-learning exposure to a psychological stressor (the Trier Social Stress Test or "TSST"; Kirschbaum, Pirke & Hellhammer, 1993) preserved or enhanced memory for emotional aspects of the slide show, but impaired memory for neutral aspects of the slide show. Moreover, stress exposure disrupted memory for information that was visually and thematically central to the slide show. Memory for peripheral information, on the other hand, was unaffected by stress. Experiment 2 replicated these results and extended them to a similar paradigm, where participants viewed separate emotional and neutral slide shows, and saliva was tested for the stress hormones cortisol and norepinephrine. Similar to the results of Experiment 1, stress disrupted memory for the neutral slide show, but enhanced memory for the emotional slide show. Salivary cortisol levels at retrieval were negatively correlated with memory for the neutral slide show. These results are consistent with theories invoking differential effects of stress on brain systems responsible for encoding and retrieving emotional memories (the amygdala) and non-emotional memories (e.g. the hippocampal formation, frontal cortex), and inconsistent with the view that memories formed under high levels of stress are qualitatively the same as those formed under ordinary emotional circumstances. These data, which are also consistent with results obtained in a number of studies using animals and humans, have implications for the traumatic memory debate and theories regarding human memory.

ABSTRACT With aging, changes in the immune system, makes cognitive performance, and the prevalence of stressors can lead to poorer overall functioning. Within the immune system, a balance should exist between cytokines regulating Th1 and Th2 immune responses; however, age-related declines in the endocrine and immune systems can disrupt this equilibrium. Several studies report higher levels of Th1 associated cytokines in inflammatory conditions of the brain, whereas fewer studies remark on Th2 associated cytokines and cognitive functioning. Declining cognitive abilities are a common concern that accompanies advancing age and some research has suggested the prevalence and impact of stressors lead to poorer performance. Participants included 92 older adults (M = 74.05 years) who completed tests of cognitive performance and stress measures, and 41 persons who had valid data on Th1 and Th2 cytokines. The results indicated that increasing age is significantly associated with several cognitive domains including executive functioning, speed of processing, and episodic memory. As hypothesized, moderation analysis revealed the relationship between Th1 and Th2 cytokinic profiles, as denoted by the IFN-γ/IL-4 ratio, is a significant moderator between stress and cognitive performance. Specifically, immune profiles skewed towards Th1 predict a significant amount of variation between high stress scores and low cognitive performance, whereas this was not found for immune profiles skewed towards Th2. Overall, the current study suggests that a pro-inflammatory state permits stress to exert a negative influence on cognitive performance.

Titel: "Fighting Freakin’ Voldemort" – En kvalitativ studie om hur The Harry Potter Alliance kommunicerar med sin målgrupp Författare: Louise Åslund och Magdalena Nyberg   Kurs, termin och år: Medie- och Kommunikationsvetenskap GR (C), C-uppsats. HT13 Handledare: Elisabet Ljungberg   Antal ord: 18 188   Problemformulering och syfte: Den här studien behandlar temat fanaktivism ur ett organisationsperspektiv och undersöker hur The Harry Potter Alliance (HPA) genom att anspela på gemensamma intressen väcker ett samhällspolitiskt intresse och engagemang hos sina anhängare. I och med detta berör uppsatsen ämnen som kan komma att ha betydelse för hur framtidens kommunikatörer skapar och bevarar trovärdiga och starka relationer med sina målgrupper i ett globaliserat, digitalt och nöjesorienterat samhälle. Studiens syfte är att undersöka hur HPA arbetar med relationsskapande och mobiliserande kommunikation i sina kanaler på Youtube och Facebook.   Metod och material: Studien genomfördes med hjälp av kvalitativa textanalyser av HPA:s Facebookinlägg och Youtubevideor från åren 2010 och 2013. Urvalet skedde inom ett par på förhand identifierade icke uteslutande kategorier av kommunikation som vi ansåg täckte in alla olika typer av kommunikation (exempelvis citat, vlog, kampanjinformation, aktuellt tema, hänvisning till övriga sociala medier, samhällsinformation, samarbete med kändisar och kampanjinformation).   Huvudresultat: Resultatet av studien är att HPA:s kommunikation är målgruppsanpassad och ständigt cirkulerar kring ett gemensamt intresse för populärkultur och samhällsengagemang. Aktivismen HPA praktiserar och deltar i hanterar de ungas brist på politiskt engagemang och visar andra sätt att engagera sig än genom de parlamentariska partiernas ungdomsförbund. I den kommunikation där syftet är att bygga relationer snarare än att mobilisera fokuserar HPA på ämnen som ligger målgruppen nära, vare sig det är fiktion, innehållsvärld eller ett aktuellt tema. I mobiliserande syften anpassas kommunikationen efter samhällsproblemets grad av abstraktion (behov av förklaring) och organisationens planerade inblandning (kampanj eller bara upplysning). Ju mer förståelse och engagemang som krävs kring en fråga, desto viktigare verkar det vara för HPA att använda populärkultur för att förklara och engagera.     Nyckelord: Aktivism, fanaktivism, nördar, fans, The Harry Potter Alliance, HPA, fiktion, målgruppsanpassad kommunikation, mobilisering, populärkultur.

Os hidrocarbonetos policíclicos aromáticos (HPA) são amplamente estudados na área de meio ambiente, em diversas matrizes ambientais como ar, água, solo e sedimento, devido a sua toxicidade, potencial mutagênico e carcinogênico. Por conta disto, as agências ambientais de países desenvolvidos listaram dezesseis HPA como sendo poluentes prioritários. As legislações a nível mundial não estipulam limites para estes compostos para ar ambiente, somente para emissões de fontes fixas e móveis e ambientes ocupacionais, mas existem diversos estudos, mais especificamente para os 16 prioritários HPA e muito pouco para os homólogos alquilados. Os HPA alquilados são mais abundantes, persistentes e frequentemente mais tóxicos que os não alquilados e a toxicidade aumenta com o número de substituições alquil sobre os núcleos aromáticos. As legislações ambientais em todo o mundo não realizam o controle em nenhuma matriz ambiental para os HPA alquilados. Neste trabalho foi desenvolvido um método para análise dos HPA e seus homólogos alquilados, utilizando cromatografia de fase gasosa acoplado a um detector de espectrometria de massa e com um sistema de injeção para grande volume, associado à vaporização com temperatura programada, que permitiu um nível de detecção na faixa de 0,70 até 103,6 ng mL-1, sendo possível analisar as amostras de material particulado oriundas de emissões veiculares. As amostras foram coletadas de acordo com a Norma ABNT NBR14489, em um dinamômetro de bancada para motor do ciclo diesel (Ciclo de 13 pontos). Os resultados encontrados foram na faixa de 0,5 ng mL-1 até 96,9 ng mL-1 Os resultados indicaram que motores a diesel/ biodiesel têm uma contribuição muito grande na formação destes HPA e homólogos alquilados