[pt] A suscetibilidade ao estresse é ditada por fatores externos e internos. Fatores externos estão associados a variáveis ambientais, enquanto os internos estão relacionados à função cerebral, cognição, constituição genética e epigenética e ao microbioma. Nesta tese, investigamos a influência das respostas individuais de enfrentamento ao medo sobre os efeitos do estresse crônico e sua modulação por uma dieta rica em calorias. Nesse intento, foram usadas as linhagens de cruzamento bidirecional Carioca como modelos de respostas opostas ao medo contextual condicionado. Inicialmente, caracterizamos essas linhagens quanto às suas respostas de congelamento após a aprendizagem e a extinção de medo. Em seguida, descrevemos em uma meta-análise o envolvimento da via serotoninérgica, importante mecanismo nos transtornos de ansiedade e medo, nos efeitos do estresse crônico. Finalmente, demonstramos que o estresse crônico tem efeitos mais fortes em ratos Cariocas de alto congelamento (CHF), alterando o equilíbrio entre as respostas de enfrentamento ativas e passivas em vários paradigmas comportamentais; por outro lado, os ratos Carioca de baixo congelamento (CLF) são minimamente afetados. Além disso, uma dieta suplementada com alimentos ricos em açúcar e gordura pode proteger os ratos CHF contra os efeitos do estresse crônico. Assim, demonstramos os efeitos adversos do estresse crônico em um modelo de transtorno de ansiedade generalizada e propomos que a suscetibilidade ao estresse está ligada à características individuais e inatas de medo e de transtorno de ansiedade, podendo ser alvo de novas terapias para transtornos de humor. / [en] Susceptibility to stress is dictated by external and internal factors. External factors are associated with environmental variables, whereas the internals are related to brain function, cognition, genetic and epigenetic constitution and the microbiome. In this thesis, we investigated the influence of the individual background underlying fear-coping responses on the effects of chronic stress and its modulation by a palatable diet. We used the Carioca bidirectional breeding lines as models of opposing conditioned contextual fear responses. At first, we characterize these lines concerning their freezing responses after fear learning and extinction. Then, we describe in a meta-analysis the involvement of the serotoninergic pathway, an important mechanism in anxiety and fear disorders, in the effects of chronic stress. Following, we demonstrate that chronic stress has stronger effects in the Carioca high-conditioned freezing (CHF) rats, altering the balance between active and passive coping responses in several behavioral paradigms; conversely, the Carioca low-conditioned freezing (CLF) rats are barely affected. Moreover, a diet supplemented with high-sugar and high-fat food can protect the CHF against the effects of chronic stress. Thus, we demonstrate the increased harmful effects of chronic stress in a model of generalized anxiety disorder and propose that susceptibility to stress is linked to fear and anxiety individual innate characteristics, which can be the target of novel therapies of mood disorders.

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat (SD) with two weeks of chronic light was more effective at inducing PTSD-like behavior symptoms and causing changes in LTP levels in the ventral hippocampus, amygdala, and prefrontal cortex between stressed and non-stressed rats. For the prophylactic treatment, propranolol and mifepristone were administered one week prior to and throughout the two weeks of the social defeat protocol. The drugs were able to prevent the changes due to stress on LTP in the three aforementioned brain regions, but did not change the anxious behavior of the rats. An enzyme-linked immunosorbent assay (ELISA) was used to determine corticosterone and norepinephrine levels between the different groups of rats. No significant differences were detected between SD and control rats, but SD injected rats were different from controls indicating that the injections were causing added stress. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in the adrenergic, corticoid, AMPA, and NMDA receptors. There were a few significant changes to some of the targets indicating that the stress protocol and drugs were having an effect on the mRNA expression. Propranolol and mifepristone could possibly be used as a prophylactic treatment for traumatic stress. In a separate study, techniques were used to determine the negative effects chronic stress (non-PTSD-like) has on synaptic plasticity in the dorsal hippocampus and to show how exercise was able to mitigate some of those negative stress effects. Electrophysiology showed differences in LTP between four groups of mice: sedentary no stress (SNS), sedentary with stress (SWS), exercise with stress (EWS), and exercise no stress (ENS). SWS had the lowest amount of LTP, whereas ENS had the highest. SNS and EWS had similar levels of LTP, which were in between the SWS and ENS groups. Corticosterone blood levels measured by an ELISA showed significant increases in the stressed groups compared to the non-stressed groups. The radial arm maze showed that both groups of exercise mice made fewer reference memory errors the second week of testing compared to the sedentary groups. RT-qPCR determined that brain-derived neurotrophic factor (BDNF) and corticoid and dopamine 5 receptors were likely causing some of the memory changes.

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat (SD) with two weeks of chronic light was more effective at inducing PTSD-like behavior symptoms and causing changes in LTP levels in the ventral hippocampus, amygdala, and prefrontal cortex between stressed and non-stressed rats. For the prophylactic treatment, propranolol and mifepristone were administered one week prior to and throughout the two weeks of the social defeat protocol. The drugs were able to prevent the changes due to stress on LTP in the three aforementioned brain regions, but did not change the anxious behavior of the rats. An enzyme-linked immunosorbent assay (ELISA) was used to determine corticosterone and norepinephrine levels between the different groups of rats. No significant differences were detected between SD and control rats, but SD injected rats were different from controls indicating that the injections were causing added stress. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in the adrenergic, corticoid, AMPA, and NMDA receptors. There were a few significant changes to some of the targets indicating that the stress protocol and drugs were having an effect on the mRNA expression. Propranolol and mifepristone could possibly be used as a prophylactic treatment for traumatic stress. In a separate study, techniques were used to determine the negative effects chronic stress (non-PTSD-like) has on synaptic plasticity in the dorsal hippocampus and to show how exercise was able to mitigate some of those negative stress effects. Electrophysiology showed differences in LTP between four groups of mice: sedentary no stress (SNS), sedentary with stress (SWS), exercise with stress (EWS), and exercise no stress (ENS). SWS had the lowest amount of LTP, whereas ENS had the highest. SNS and EWS had similar levels of LTP, which were in between the SWS and ENS groups. Corticosterone blood levels measured by an ELISA showed significant increases in the stressed groups compared to the non-stressed groups. The radial arm maze showed that both groups of exercise mice made fewer reference memory errors the second week of testing compared to the sedentary groups. RT-qPCR determined that brain-derived neurotrophic factor (BDNF) and corticoid and dopamine 5 receptors were likely causing some of the memory changes.

This study aimed to understand subjective cognitive decline (SCD) and functional difficulties in older age cohorts with depressive symptoms, using one scoping review and two empirical studies. We implemented the six steps of Arksey and O'Malley's procedure for the scoping review. We used the population, concept, and context (PCC) inclusion and exclusion criteria in the literature search across MEDLINE via Ebscohost, PubMed, and PsycINFO for articles published on ADL/IADL indicators of SCD in older adults with depressive symptoms and that published in English language journals from January 2011 to November 2021. The two empirical studies used the 2019 wave of the Behavioral Risk Factor Surveillance Survey dataset of older adults aged 65 and ≥ 80 from the Centers for Disease Control and Prevention. We used multiple regression and the bias-corrected percentile bootstrap with 5000 samples using standard path-analytic approaches for the moderated mediation for the two empirical studies. Findings supported that instrumental activities of daily living (IADLs) presented more difficulties for older adults with SCD than the basic activities of daily living (B-ADLs), given that IADLs require more cognitive capabilities than B-ADLs. Environmental factors like healthcare access and subjective functional difficulties predicted SCD by mentally unhealthy day (MUD) mediation and age cohort moderation. The middle age cohort (70–74) had the most pronounced effects of the MUDs mediation in the relationship between healthcare access and IADLs in older adults with SCD. The younger-old (65–69) showed more substantial MUD mediation effects in the relationship between subjective functional difficulties and SCD. Worse SCD was associated with being Asians, female older adults, and at lower education years and income levels. Findings profiled SCD indicators in daily living activities across age cohorts and the mentally unhealthy days presentation. We extend the chronic stress theory predictions on accentuated emotional vulnerability from increased functional difficulties, compounding SCD.

No description available.

Social work practice in child welfare is widely acknowledged as a challenging field. Most social workers who choose to enter this field of practice do so with the knowledge that they will be exposed to difficult, at times traumatic, situations. They expect that the job will be stressful; that they will need to manage complex and challenging cases; and they will do so with few resources and often little public support. They also expect to be supported by their workplace in carrying out their mandated roles, however increasingly, a disconnect exists between those administer child welfare services and their understanding of front-line work (Herbert, 2007). Social workers’ wellbeing in child protection practice is directly affected by workplace culture; a subject that is often unexamined when addressing the high turnover of staff in the field. Instead, workers who leave child welfare practice – as well as though who stay while experiencing compassion fatigue or vicarious trauma - are viewed by administrators as being unsuitable for the work, a way of individualizing systemic issues (La Rose, 2009). This study sought to understand the ways that the culture of the workplace contributes to worker experiences of vicarious trauma, compassion fatigue and burnout. Survey research was conducted anonymously with child protection workers in Southern Ontario to understand the aspects of workplace culture that child welfare workers find helpful and supportive in managing the day-to-day of their work, as well as in addressing mental health in the workplace. From the seventy responses that were received, a number of themes emerged including Workplace Culture; Worker Well-being; Agency Support; Safety; Systemic Issues and Training. In this study, participants identified informal peer support and reflexive, supportive supervision as key areas that either sustained their practice or worsened their experiences. Workplace culture emerged as a significant factor in determining worker well-being and resiliency. Survey participants provided examples that illustrated clearly the ways in which neo-liberal policies and austerity measures have contributed to a workplace culture in which workers expressed feeling replaceable, devalued, and in precarious situations. Cutbacks to services and staffing, crushing workload and increasingly complex client situations contribute to the sense of being overwhelmed experienced by workers. Addressing experiences of compassion fatigue and vicarious trauma requires a paradigm shift from exclusively individual responsibility and towards an understanding of the broader systemic context and organizational responsibility (Antonopoulou, 2017; Mathieu, 2012; van Dernoot Lipsky, 2009). Organizational strategies to support worker wellbeing are shown to be significant factors in addressing and preventing compassion fatigue and vicarious trauma, ultimately preventing burnout and staff turnover. / Thesis / Master of Social Work (MSW)

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015

Si les modifications dans l’expression et les propriétés des mucines ont été largement décrites dans la physiopathologie des maladies inflammatoires chroniques de l’intestin, la caractérisation structurale et fonctionnelle de la barrière de mucus reste parcellaire dans le contexte micro-inflammatoire du syndrome de l’intestin irritable (SII). Par ailleurs, certains traitements probiotiques préviennent la rupture de l’intégrité de la barrière épithéliale intestinale, provoquée en conditions de stress mais peu de travaux décrivent leur influence sur les modifications de la structure du mucus, induites par le stress. Cette étude a comme objectifs d’évaluer chez le rat (i) si un stress chronique modifie le nombre de cellules à mucus et l’expression de la mucine Muc2, ainsi que la nature biochimique des mucines secrétées au niveau de l’iléon et du côlon, et plus particulièrement les O-glycanes, (ii) si un traitement probiotique (Lactobacillus farciminis) prévient les modifications du mucus potentiellement induites, (iii) si les effets observés sont en lien avec la capacité de colonisation in vivo de L. farciminis.Méthodes. Des rats Wistar mâles ont reçu L. farciminis ou une solution saline. Les animaux ont été soumis au stress d’évitement passif de l’eau (WAS) pendant 1h/jour ou à un stress fictif (contrôle), pendant les 4 derniers jours des traitements. Différents prélèvements ont été effectués au niveau de l’iléon et du côlon pour (i) des analyses sur coupes (immuno-marquage, nombre de cellules à mucus) et (ii) la détermination du profil de O-glycosylation des mucines. La morphologie de la couche de mucus a été évaluée par microscopie à force atomique (AFM). L. farciminis a été visualisé par "Fluorescence in situ Hybridization", confirmée par qPCR et son adhésion à la muqueuse a été déterminée par une méthode ex situ. La perméabilité paracellulaire et la sensibilité viscérale ont été évaluées.Résultats. Le WAS ne modifie pas le nombre de cellules à mucus ni l’expression de la mucine Muc2 aux niveaux iléal et colique. L’analyse par spectrométrie de masse a révélé que le stress induit des altérations de la O-glycosylation des mucines. Une augmentation marquée du degré de complexité des structures glycaniques a été observée, se traduisant par l’apparition de chaînes polylactosaminiques, sans modification toutefois du taux de sialylation et de sulfatation des mucines. La couche de mucus en condition de stress, observée par AFM, présente une morphologie aplatie et moins cohésive. L'hypothèse serait que les modifications structurales des O-glycanes influencent les interactions physico-chimiques entre les fibres de mucines, impactant de manière négative l’intégrité de la barrière de mucus. Cette altération de la couche de mucus s'accompagne d'un défaut de la barrière épithéliale et d'une hypersensibilité viscérale. L’administration de la souche probiotique prévient ces changements provoqués par le WAS. L. farciminis a été retrouvé au sein de l’iléon et du côlon. Par ailleurs, la présence de "Segmented Filamentous Bacteria" (SFB) a été mise en évidence, par FISH et microscopie électronique, au niveau de l’iléon sur l'ensemble des animaux testés. Le traitement par L. farciminis induit une diminution de la population des SFB aussi bien chez les animaux contrôles que stressés. Conclusion. Nous avons montré qu’un stress chronique chez le rat, outre les modifications fonctionnelles de l'épithélium intestinal (hyperperméabilité intestinale et hypersensibilité viscérale), altère la structure O-glycanique des mucines sans affecter l’expression de Muc2. Ces altérations se traduisent par une perte des propriétés cohésives de la couche de mucus. La souche probiotique L. farciminis, en prévenant l’ensemble des modifications induites par le stress, contribue au renforcement de la fonction barrière de l'intestin. Cette étude fournit un argumentaire complémentaire pour l’utilisation de cette souche dans le traitement du SII. / Background. Despite a large body of literature incriminating mucus alterations in the pathogenesis of Intestinal Bowel Diseases (IBD), structural and physical changes in the mucus layer remain poorly understood in the micro-inflammatory context of Irritable Bowel Syndrome (IBS). Moreover, some probiotic treatments prevent stress-induced intestinal epithelial barrier impairment but little is known about their influence on intestinal mucin structural modifications and mucus properties induced by stress. Thereby, this study aimed at evaluating whether (i) a chronic stress modified the number of gut goblet cells and Muc2 expression, nature of secreted mucins in both ileum and colon and more particularly mucin O-glycosylation, (ii) L. farciminis treatment prevented these alterations and (iii) observed effects were related to the in vivo colonization capacity of L. farciminis.Methods. Wistar rats received orally L. farciminis (1011 UFC/day) or vehicle (NaCl 0.9% (w/v)) for 14 days. From day 10 to day 14, they were submitted either to sham (control) or 4-day Water Avoidance Stress (WAS) during 1 hour per day. After sacrifice, different samples (tissues, mucosa) were collected in both ileal and colonic regions for (i) histological analyses (Muc 2 immunohistochemistry, number of goblet cells by Periodic Acid Schiff/Hemalun) and (ii) O-glycosylation profile by mass spectrometry after mucin extraction and purification. In parallel, the morphology of the mucus layer was evaluated by atomic force microscopy. Spatial localization of L. farciminis was assessed by Fluorescence In Situ Hybridization (FISH), confirmed by qPCR. Mucosal adhesion of L. farciminis was determined by an ex situ method. In complement, intestinal paracellular permeability and visceral sensitivity were measured.Results. WAS did not modify neither the number of intestinal goblet cells nor Muc2 expression in both ileum and colon. In contrast, the mass spectrometry analysis demonstrated that O-glycosylation of mucins was strongly affected by WAS. Indeed, a strongly increase in the complexity degree of O-glycan structures was observed in both ileum and colon, with the appearance of elongated polylactosaminic chains (repetition of the disaccharidic unit composed of galactose and N-acetylglucosamine), without modifications of mucin sialylation and sulfation. Under stress conditions, the mucus layer, observed by atomic force microscopy, showed a flattened morphology, probably indicative of a loss in its cohesive properties. We hypothesized that O-glycan structural modifications influence physico-chemical interactions between mucins fibers. Stress also induced intestinal hyperpermeability and visceral hypersensitivity. The mucus layer alteration was, thus, in relation with epithelial barrier impairment and visceral hypersensitivity. L. farciminis administration prevented WAS-induced functional, biochemical and physical changes of mucus. The presence of L. farciminis in the ileum and colon was detected by FISH and qPCR, albeit with quantitative and qualitative differences in the colonization capacity within these two intestinal compartments. Furthermore, the presence of Segmented Filamentous Bacteria (SFB) was shown in the ileum whatever the conditions under study. L. farciminis reduced the SFB population level in both control and stressed animals.Conclusion. Chronic stress induced functional changes (intestinal hyperpermeability and visceral hypersensitivity) in rats, as well as a shift in mucin O-glycosylation rather than changes in mucin expression. Intestinal mucin O-glycan modifications resulted in a loss of mucus layer cohesive properties. L. farciminis treatment prevented impairment of both intestinal epithelial and mucus barriers, reflecting an enhancement of the protective barrier function. These results confirm that L. farciminis is a valuable probiotic in the IBS management.

憂鬱症是盛行的精神疾病之一。慢性疼痛或是處在長期壓力情境的患者常與憂鬱症產生共病。在動物研究中，類鴉片delta受體制效劑能產生抗憂鬱效果，並且在發炎性疼痛的研究也指出類鴉片delta受體制效劑能展現抗痛覺過敏的效果。本研究主要利用大白鼠腦室內給予類鴉片delta受體制效劑SNC80以及三環抗憂鬱劑amitriptyline，來探討並比較其所產生的抗憂鬱效果在發炎性疼痛或長期壓力情境下與正常情境下的異同。大白鼠強迫游泳試驗被用來比較測試藥物的抗憂鬱效果；佛氏完全佐劑經由皮下注射至大白鼠右後腳掌底板來產生發炎性疼痛；腎上腺皮質酮經由皮下注射且持續21天來產生長期性壓力；西方墨點法用來檢驗在發炎性疼痛或長期壓力下，類鴉片delta受體蛋白質在大白鼠海馬迴的細胞膜上的改變。另外，拮抗劑實驗則用來確認類鴉片delta受體所產生的抗憂鬱效果。實驗結果顯示，大白鼠在正常情境下，SNC80及amitriptyline皆能產生抗憂鬱效果；然而在發炎性疼痛下，SNC80所產生的抗憂鬱效果有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也隨著疼痛的時間增長而增加，amitriptyline則跟正常情境下的效果相似。另外，大白鼠在長期性壓力下，SNC80的抗憂鬱效果則沒有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也未受到改變。本研究透過行為實驗提出類鴉片delta受體制效劑的藥理特性，並用分子生物學的方法來對應行為實驗的結果。本研究可做為未來類鴉片delta受體制效劑在治療慢性疼痛的憂鬱症患者上，可能發展為抗憂鬱藥的一個證據。 / Depression is one of the most prevalent mental illnesses all over the world. Patients with chronic pain or stress often have depression. Previous studies have shown that delta opioid receptor (DOR) agonists produced antidepressant-like effects in animal models and that antihyperalgesic effects of DOR agonists can be enhanced in rats under inflammatory pain. The aim of the study was to investigate and compare the antidepressant-like effects of a DOR agonist, SNC80, and a tricyclic antidepressant, amitriptyline, following intracerebroventricular (i.c.v.) administration in rats under different states. The forced swim test was used to determine the antidepressant-like effects of test compounds. Complete Freund’s adjuvant was injected subcutaneously into the right hind paw of rats to elicit inflammatory pain. Corticosterone was injected subcutaneously once per day for 21 days to induce chronic stress. The western blot was used to quantify the levels of DOR protein on plasma membrane in the hippocampus of rats under inflammatory pain or chronic stress. In addition, antagonist experiment was conducted to verify the receptor mechanism underlying the antidepressant-like effects of DOR agonist. Results indicated that i.c.v. SNC80 and amitriptyline dose-dependently produced antidepressant-like effects in rats under normal state. More importantly, the potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. In addition, up-regulation of supraspinal DORs was time-dependently associated with enhanced antidepressant-like effects of SNC80 in rats under inflammatory pain. On the other hand, SNC80 did not produce enhanced antidepressant-like effects, and DOR density was not changed in rats under chronic stress. This study provides evidence of the DOR agonist’s state-dependent effects and suggests that DOR agonists may be more effective as potential antidepressants for patients with depression comorbid with chronic pain.