Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Following decades of research on stress and its impact on behaviour, it is now widely accepted that selective psycho-pathologies, in particular clinical depression are more prevalent in humans with prior history of life-stress events. Interest in stress has led to questions about how it might affect the physiology and behaviour of animals exposed indirectly during gestational development. Not unexpectedly gestational stress has been shown to affect the offspring in several ways: endocrine responses to stress are elevated, fear, arousal and affective disturbances are all subject to vary if the pregnant animal is subjected to periods of aversive stimulation. Beginning in 1997, Michael Meaney of McGill University produced a series of publications suggesting that peri-natal events influence offspring and infant development, not via physical discomfort or physiological disturbance, but does so through modifications of maternal behaviour. Highly nurturant mothers (those who engage in active arched-back nursing (ABN), and spend more time licking and grooming (L/G) their pups), programme their offspring with improved cognitive abilities, decreased anxiety and fear, and reduced HPA axis hormone secretion. Low-nurturant mothers, who engage in less ABN and less L/G, tend to programme the opposite responses in their offspring. Our initial foray into this field was to investigate if gestational stress might also produce responses in the offspring via changes in maternal behaviour, and indeed ABN and L/G were reduced in dams which were subjected to gestational stress. We queried why stressed Dams would be less maternal towards their infants, and tested gestationally-stressed Dams in the Porsolt test for depressive-like behaviour. Our results suggested that these stressed Dams were actually depressed and this resulted in less maternal behaviour. Human mothers with depression are also less maternal and have been shown to divest themselves of infant care much like our prenatally-stressed Dams. On this basis we have proposed that gestational stress induced decrements in maternal behaviour represent a novel rat model for postnatal depression with face and construct validities. In the present work we have attempted to replicate the findings of Smythe's group (Smith et al., 2004), and have investigated the potential for antidepressants to alter the influence of gestational stress on maternal behaviours and depressive-like response, and whether or not the offspring are modified by maternal treatment with ant-depressants. Approximately 140 time-mated, lister hooded rats were generated in house, and subjected to gestational stress on days 10-20 (1hr restraint/day) or remained undisturbed in their home cages. Following birth, cohorts of control and stressed Dams were administered vehicle or an antidepressant (imipramine 15mg/kg; or sertraline 10mg/kg) once daily until postnatal day 10. We assessed maternal Porsolt activity, nurturance (ABN, L/G, nest building) and anxiety-like behaviour in the elevated plus maze (EPM). Representative offspring of each Dam's treatment conditions were maintained post weaning and assessed in the Porsolt and EPM to determine if any changes in maternal behaviour elicited by the antidepressants altered their behavioural programming. Our findings confirm that Dams show depressive-like symptoms following gestational stress, and that administration of antidepressants to the Dams reduces depressive-like behaviour and increased maternal care. We propose that rat gestational stress is a putative model for human postnatal depression. Prenatal stress effects on maternal behaviour in the rat Dam represent a novel, and innovative model for human postnatal depression.

The lumbar motor activity in isolated spinal cords of 72 postnatal Balb/C mice aged 2, 5, 10 and 21 days (PN2-21) was electroneurographically recorded (ENG) via bilateral ventral roots following treatment with three different concentrations (25, 100 and 200 pM) of the neurotransmitter, 5-hydroxytryptamine (5-HT), i.e., serotonin, to determine its effects on spinal pattern generation.

La carence précoce en donneurs de méthyles (folates et vitamine B12) entraîne une hyperhomocystéinémie ainsi que des troubles cognitifs et de la coordination motrice chez les ratons de 21 jours. Ces troubles ont été reliés à une altération de la neurogenèse dans l'hippocampe et le cervelet, mécanisme étroitement relié à la neurostéroïdogenèse (NSG), définie par la synthèse locale de stéroïdes dans le cerveau. L'objectif principal de ce travail a été de déterminer si ces troubles étaient associés à une altération de la NSG. Ce travail a conduit à plusieurs résultats marquants, montrant notamment l'effet délétère de la carence gestationnelle en donneurs de méthyles sur la voie stéroïdogénique dans le cervelet, région cérébrale particulièrement vulnérable en période post-natale. Ceci s'est traduit par un effondrement du contenu en estradiol et autres neurostéroïdes, consécutivement à la diminution de l'expression de StAR, TSPO et de l'aromatase, ainsi que des récepteurs aux estrogènes. Ces effets délétères sont associés à une atteinte de la voie de signalisation dépendante de l'AMPc associée à l'activation du récepteur LHR, et la diminution de facteurs de transcription impliqués dans la régulation des gènes de la NSG, notamment SF-1, dont la présence dans les cellules de Purkinje du cervelet n'avait jamais été décrite auparavant. Cette réponse à la carence se ferait selon un dimorphisme sexuel, puisque seules les jeunes femelles nées de mères carencées étaient affectées. Enfin, ces études ont permis la mise en évidence d'altérations fonctionnelles associées aux dommages cellulaires et moléculaires observés dans les bulbes olfactifs (BO), se traduisant par une diminution des fonctions de la discrimination olfactive. Ceci pourrait contribuer au retard de croissance associé au poids corporel réduit mesuré chez les animaux carencés / Early methyl-donor deficiency (MDD, folate and vitamin B12) produces hyperhomocysteinemia, cognitive and motor disorders in 21 days-old rat pups. These disorders are linked to an alteration of neurogenesis in the cerebellum and the hippocampus, which is closely linked to neurosteroidogenesis, defined as the local synthesis of steroids in brain. The aim of this work was to verify if these troubles are associated with an altered neurosteroidogenesis. This work led to several striking results, showing in particular the deleterious effects of the methyl donor deficiency on the steroidogenic pathway in the cerebellum, particularly vulnerable during postnatal development. This was confirmed by the reduced contents of estradiol and other neurosteroids, as a result of the decrease of the expression of StAR, TSPO and aromatase, as well as the estrogen receptors. These deleterious effects are associated to the impairment of AMPc dependent signaling pathway and the decrease of transcription factors, notably SF-1, which the presence in the cerebellar Purkinje cells had never been described previously. This response to the deficiency would be made according to a sexual dimorphism, since only the young deficient females were affected. Finally, these studies allowed us to show functional changes associated with the cellular and molecular damage observed in the olfactory bulbs, being traduced by a decrease of the olfactory discrimination. This could contribute to the growth retardation associated with the reduced body weight of the deficient animals

Very severe maternal obesity (BMI > 40kg/m2) increases significantly the risks of poor pregnancy outcomes for both mothers and babies. In light of the limited success of behavioural interventions to date in improving outcomes in very severely obese women, this study sought to gain an understanding of women's beliefs and experiences regarding weight, health and pregnancy, within the context of their everyday lives. Qualitative serial interviews were conducted with eleven very severely obese women during pregnancy and the postnatal period. Seven partners of the women took part in one semi-structured interview during the woman's pregnancy. Analysis took place in several stages using a thematic approach. Themes were identified within and between individual women's accounts, as well as within and between the accounts of members of couples. Participants' narratives demonstrated the ways in which they navigated the experience of high-risk pregnancy, and stigma emerged as a key theme. This research contributes new knowledge about the complex ways in which women experience ‘very severe obese' pregnant embodiment, relating to both formal and informal discourses around weight and health in pregnancy. Most undertook ‘moral accounting' in response to stigma, and several accounts resonated with Monaghan's (2006) categorisations of excuses, justifications, contrition and repudiation, in both accounting for their weight and in demonstrating their ‘fitness' for pregnancy and motherhood. Following birth, high levels of motivation to enact behaviour change were expressed, in some cases alongside repudiatory accounting regarding the associated risks and the medicalisation of very severe obesity. Participants experienced a lack of formal healthcare support in the postnatal period. Future approaches to policy and practice should consider ways in which to engage women and partners during pregnancy, exploring ways which in which stigma can be acknowledged and neutralised, in order to provide support and advice during and after pregnancy and birth, and into parenthood.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2017-04-24T14:36:33Z No. of bitstreams: 1 Clarissa Martins.pdf: 1616707 bytes, checksum: 7d6ba6c5f2c247d0a5ccd351abde1ebe (MD5) / Made available in DSpace on 2017-04-24T14:36:33Z (GMT). No. of bitstreams: 1 Clarissa Martins.pdf: 1616707 bytes, checksum: 7d6ba6c5f2c247d0a5ccd351abde1ebe (MD5) Previous issue date: 2014-10-28 / This dissertation refers to an epidemiological study of screening scales for depression in pregnant adolescents. The main objective of the research was to adjust the cutoff scales for screening for depression, Edinburgh Postnatal Depression Scale (EPDS) and Beck Depression Inventory (BDI), for pregnant teenagers. It is a cross-sectional, population-based study carried out with pregnant adolescents (10-19 years old), which consulted the service prenatal Unified Health System (SUS) of Pelotas. Was carried out from October 2009 to March 2011. The sample was composed based on the SIS-Prenatal program records along the municipal health department and the Basic Health Units, and specialized clinics in the urban area of Pelotas / RS. The women answered a questionnaire with socio demographic and obstetric data, besides the two scales for screening for depression during pregnancy. Also participated in a structured clinical interview Mini International Neuropsychiatric Interview 5.0 (MINI) for the clinical diagnosis of depression. Demographic, obstetric and psychiatric social variables were assessed according to the WHO questionnaire. The accuracy of the scales was calculated by their Area under the curve (AUC) of ROC, as well as their respective sensitivity, specificity and predictive values. The best cutoff (PC) found for this sample was ≥10 EPDS scale, with sensitivity 81.1% and specificity 82.7% and AUC of 0.899. BDI for the best cutoff point was ≥11, sensitivity 81.1%, sensitivity 76.8% and an AUC of 0.869. Since the difference between the two AUC were statistically significant (p = 0, 0215). Based on the results, it is concluded that the EPDS scale has become more predictive and sensitive in screening for depression in pregnant adolescents, with respect to BDI. / A presente dissertação refere-se a um estudo epidemiológico sobre escalas de rastreamento para depressão em gestantes adolescentes. O objetivo principal da pesquisa foi verificar os pontos de corte das escalas para rastreamento da depressão Edinburgh Postnatal Depression Scale (EPDS) e Beck Depression Inventory (BDI), em gestantes adolescentes. Trata-se de um estudo transversal, de base populacional, realizado com gestantes adolescentes (10 a 19 anos de idade), as quais consultaram o serviço de pré-natal do Sistema Único de Saúde (SUS) de Pelotas-RS. Desenvolvido no período de outubro de 2009 a março de 2011. A amostra foi composta com base nos registros do programa SIS-Pré-Natal, junto a secretaria municipal de saúde e nas Unidades Básicas de Saúde, além de ambulatórios especializados na zona urbana de Pelotas/RS. As gestantes responderam a um questionário com dados sócio demográfico e obstétricos, além das duas escalas para o rastreamento da depressão durante a gestação. Também participaram de uma entrevista clínica estruturada Mini Internacional Neuropsychiatric Interview 5.0 (MINI) para o diagnóstico clínico da depressão. As variáveis sócio demográficas, obstétricas e psiquiátricas foram avaliadas nos domínios do questionário da OMS. A precisão das escalas foi calculada através de suas Áreas sob a curva (AUC) de ROC, assim como suas respectivas sensibilidade, especificidade e valores preditivos. O melhor ponto de corte (PC) encontrado para esta amostra na escala EPDS foi ≥10, com sensibilidade 81,1% e especificidade 82,7% e AUC de 0,899. Para a escala BDI o melhor ponto de corte foi ≥11, sensibilidade 81,1%, sensibilidade 76,8% e uma AUC de 0,869. Sendo que a diferença entre as duas AUC mostraram-se estatisticamente significativas (p=0,0215). Com base nos resultados, conclui-se que a escala EPDS apresenta-se mais preditiva e sensível no rastreamento para depressão em gestantes adolescentes, quando contrastada com a escala BDI.

Puerperal Psychosis is the most severe form of postnatal psychiatric illness, and is a psychiatric emergency. Human-based research to find a means of genetically predicting a woman's risk of puerperal psychosis has so far failed to reliably or reproducibly identify candidate genes or pathways, due to problems common within the field of psychiatric genetics, leading to the proposal of using an animal model in the form of Porcine Maternal Infanticide. In this project, the author has aimed to understand the pathophysiology of PMI using NGS technologies in order to 1) extend the validity of PMI as a model for PP; 2) determine future steps for development of the PMI model; and 3) generate insights into the management of PMI (and by extension PP) via prediction and detection of a puerperal trigger. These aims have been pursued via two experiments. In the first, the author has created RNA-Seq libraries from archival RNA, and then performed differential gene expression analysis. The results indicated that RNA-Seq technologies can be used with archival RNA samples, but using such samples introduces the risk of degradation-based bias. The substantial influence of outliers, confounding factors and sample size on the results prevented reliable identification of candidate genes" but provide concrete guidelines development of the Porcine Maternal Infanticide model. In the second, the author has created MBD-Seq libraries from archival tissue, and then performed differential methylation analysis. The results indicated that it is possible to use MBD-Seq technologies with Sus scrofa brain tissue. Once again, the effect of confounding factors and sample size on the results prevented reliable identification of candidate genes, but provide guidance for development of the Porcine Maternal Infanticide model.

La dépression postnatale (DPN) est un facteur de risque de trouble des interactions précoces mère-enfant et de troubles de santé mentale de l’enfant. Si les programmes de visites à domicile (VAD) en périnatalité ciblent souvent la prévention de la DPN, les résultats sont peu probants.CAPEDP est la première étude contrôlée randomisée de VAD destinée à des familles multirisques d’une telle ampleur menée en France. Ce travail en décrit les résultats sur la DPN. 440 femmes sont recrutées et randomisées en deux groupes : primipares, âgées de moins de 26 ans, et au moins un facteur de risque parmi : un faible niveau d’éducation, des revenus faibles et/ou être isolées. Le groupe intervention bénéficie de VAD menées par des psychologues du troisième trimestre de grossesse aux deux ans de l’enfant. La symptomatologie de la DPN est évaluée à l’inclusion et 3 mois après la naissance avec l’Edinburgh Postnatal Depression Scale (EPDS). A 3 mois post-partum, les scores moyens à l’EPDS sont respectivement de 9.4 (5.4) pour le groupe contrôle et de 8.6 (5.4) pour le groupe intervention (p = 0.18). Pour certains sous-groupes de femmes ayant bénéficié de l’intervention les scores EPDS sont plus faibles que le groupe contrôle : celles avec peu de symptômes dépressifs en prénatal (EPDS<8), celles qui pensent être avec le père pour élever leur enfant, et celles avec un niveau d’éducation supérieur au BEPC. CAPEDP n’a pas démontré d’efficacité pour prévenir la DPN. Les analyses post hoc montrent que l’intervention peut être efficace pour des femmes sans certains facteurs de risque. Il serait utile de développer des recherches plus intégrées dans le dispositif de droit commun. / Postnatal maternal depression (PND) is a significant risk factor for infant mental health. Although often targeted in perinatal home-visiting programs with vulnerable families, little impact on PND has been observed. CAPEDP is the first French randomized controlled trial for multi-risk families evaluating the impact on PND symptomatology of a home-visiting intervention using psychologists in a sample of women presenting risk factors.440 women were recruited at their seventh month of pregnancy. All were first-time mothers, under 26, with at least one of three additional psychosocial risk factors: low educational level, low income, or planning to raise the child without the father. Participants were randomized into either the intervention or the control group. The intervention consisted of intensive multifocal home visits through to the child’s second birthday. The control group received care as usual. PND symptomatology was assessed at baseline and three months after birth using the Edinburgh Postnatal Depression Scale (EPDS).At three months postpartum, mean EPDS scores were 9.4 (5.4) for the control group and 8.6 (5.4) for the intervention group (p = 0.18). The intervention group had significantly lower EPDS scores than controls in certain subgroups of women: with few depressive symptoms at inclusion (EPDS<8), who were planning to raise the child with the child’s father, with a higher educational level.CAPEDP failed to demonstrate an overall impact on PND. However, post-hoc analysis reveals the intervention was effective in subgroups of women without certain risk factors. Effective overall reduction of PND symptomatology may require more tailored interventions.

N6-methyladenosine (m6A) is the most ubiquitous post-transcriptional RNA modification and has an important role in determining the fate of mRNA transcripts. Among the key proteins of the m6A pathway are methyltransferases (METTL family enzymes), demethylases (FTO, ALKBH family enzymes), and m6A binding proteins (e.g., YTHDF family) which recognize RNA sequences depending on the amount and localization of m6A in target transcripts and subsequently influence the fate of mRNA transcripts. The role of methyltransferases and demethylases is to provide a dynamic balance of m6A levels and possibly to convey mechanisms of specificity for these so-called epitranscriptomic marks, which are not yet fully understood. The main objective of this work was to determine the relative changes in the expression of key m6A pathway proteins during early postnatal development and adulthood in the rat brain. We found that the level of expression of key m6A pathway proteins decreases from birth to adulthood, with the exception of a transient increase between postnatal days 10 and 18. During this period, we also found significant changes in the expression of respiratory chain complexes. However, further research is needed to provide evidence of a mechanistic link between the m6A pathway and brain energy homeostasis during...

Orientador: Raquel Fantin Domeniconi / Resumo: O estado nutricional materno desempenha papel crucial na saúde e no bem-estar do feto. Alterações testiculares, prostáticas e espermáticas foram observadas em animais adultos, cujas mães sofreram restrição de proteína. No entanto, não há trabalhos com este modelo experimental que enfoquem o desenvolvimento, padrão de vascularização e seus reflexos na expressão de proteínas no epidídimo. O objetivo deste estudo é investigar o padrão das respostas morfológicas, imuno-histoquímicas e expressão de proteínas do epidídimo da prole de ratos Wistar de mães submetidas à restrição proteica no período de gestação e de lactação. Fêmeas prenhes foram alocadas nos grupos experimentais normoproteico (NP) e hipoproteico (HP) que receberam, respectivamente, dietas contendo 17% e 6% de proteínas durante gestação e lactação. Após o desmame, os ratos receberam dieta padrão para roedores até as idades de 21, 44 e 120 dias pós-natais (DPN) quando foram eutanasiados. Os epidídimos foram coletados e processados segundo técnicas histológicas, imuno-histoquímicas e de western blotting. Nos filhotes HP, o tamanho reduzido e baixo peso observados ao nascimento se mantiveram até o DPN 120, acompanhados da redução dos órgãos do sistema genital masculino para todas as idades analisadas. A dieta hipoproteica materna diminuiu os níveis séricos de testosterona nos animais no DPN 44, aumentou os níveis de aldosterona nos animais no DPN 21 e não alterou os níveis de estradiol em nenhuma das idades. Nos animais ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Maternal nutrition status plays a crucial role in the health and well-being of the fetus. Changes of testes and prostate as well as spermatic disorders were observed in adult animals whose mothers were subjected to protein restriction. However, there are no studies with this experimental model that focus the development and the vascular pattern of epididymis, as well as their reflexes in the expression of proteins of the epididymis. The aim of this study is to investigate the pattern of morphometric, immunohistochemical and protein expression of the epididymis of the Wistar rat offspring whose mothers were subjected to a low-protein diet during gestation and lactation. Pregnant females were divided into normoprotein (NP) group and low-protein (LP) group that received, respectively, diets containing 17% and 6% of protein during gestation and lactation. After weaning, the LP and NP male pups received the standard diet for rodents until the ages of 21, 44 and 120 days (PND), when they were euthanized. The epididymides were collected and processed according to histological, immunohistochemical and western blotting techniques. In the LP offspring, the smaller body size and low weight observed at birth remained until the PND 120, as well as the reduction of the male genital system organs weight for all analyzed ages. Maternal low-protein diet decreased testosterone serum levels in animals at PND 44, increased aldosterone serum levels in animals at PND 21 and did not altered estradi... (Complete abstract click electronic access below) / Doutor