The Environmental Stress Hypothesis (ESH) illustrates the underlying mechanisms of internalizing problems in children with Developmental Coordination Disorder (DCD), indicating that the relationship between DCD and internalizing problems could be influenced by numerous physical and psychosocial consequences. However, the potential pathways described in this conceptual framework have not been comprehensively examined. Furthermore, given that child development is a dynamic process, these pathways have not been investigated from a developmental perspective. In order to address these gaps in knowledge, this dissertation sought to advance our understanding of the ESH by examining the underlying mediating pathways connecting DCD and internalizing problems in three age groups: early childhood, late childhood/early adolescence, and young adulthood. Study 1 showed that preschool children at risk for DCD (rDCD) experience more internalizing problems than typically developing children. However, physical activity and BMI do not mediate the relationship between rDCD and internalizing problems. Overall, our findings confirm that rDCD and internalizing problems co-occur in early childhood. Nevertheless, as there is no mediation of physical activity or BMI, the underlying mechanisms may be more related to other psychosocial outcomes (e.g., self-concept or perceived social support), suggested in the ESH. Study 2 examined school-aged children and included global self-worth, one of the psychological outcomes identified in the ESH, to address one of the limitations in Study 1. Findings support the ESH by showing a sequential mediating pathway from probable DCD (pDCD), through physical activity/BMI and global self-worth, to self-reported internalizing problems. Sex was found to moderate the underlying mechanisms of internalizing problems, altering the pathways from pDCD to internalizing problems. Study 3 was conducted to test the full ESH in emerging adults. Results support the mediating effects of psychosocial well-being, including stress, global relationships, perceived social support, and self-concept, on the relationship between poor motor coordination and self-reported psychological distress in young adults. However, in this age group, physical inactivity and higher BMI, did not mediate the relationship between motor coordination and internalizing problems. In conclusion, this dissertation highlights the co-occurrence of motor difficulties and internalizing problems across three developmental stages. The underlying mechanisms of internalizing problems may differ by age and sex. It is also worth noting that compared to physical health, psychosocial well-being may play a more important role as a mediator in the relationship between motor coordination and internalizing problems. / Thesis / Doctor of Philosophy (PhD) / Developmental Coordination Disorder (DCD) or poor motor coordination has been linked to the higher levels of internalizing problems, such as anxiety and/or depression. However, the underlying mechanisms remain unclear. Although the Environmental Stress Hypothesis (ESH) provides a theoretical framework illustrating that physical and psychosocial consequences of DCD may play important roles, this model has not been comprehensively examined. Therefore, this dissertation tested different components of the ESH in three age groups (i.e., preschool age, school age, and young adulthood) in an attempt to provide a better understanding of why motor difficulties cause more internalizing problems from a developmental perspective. Findings confirm that children with DCD and adults with poor motor coordination are at greater risk for internalizing problems, and that perceptions of self may play a more important role explaining the relationship. However, the potential pathways from motor difficulties to internalizing problems may differ by sex and age. In summary, it is recommended that, in order to prevent or improve mental health problems, interventions should target improvements in self-concept, such as self-esteem, through participation in physical activity or weight control, while taking into account sex and age.

Dans ce travail de thèse, nous avons évalué les effets inflammatoires, comportementaux et cognitifs de l’exposition périnatale des souris à trois matrices alimentaires d’anguilles, reflétant 3 niveaux de pollution (faible, moyenne et haute), tout en considérant le sexe de la progéniture ainsi que les différentes phases d’âges. Les réponses inflammatoires ont été évaluées, aussi bien au niveau cérébral, y compris dans les cellules de la microglie, qu’au niveau périphérique, à 4 stades de vie distincts, et ce dès la naissance jusqu’à l’âge moyen. Chez les souriceaux, mâles et femelles, dont leurs génitrices ont consommé de l’anguille contaminée, durant la période gestationnelle et lactationnelle, vs les témoins dont leurs mères ont consommé uniquement la diète standard, nos résultats ont montré une neuro-inflammation précoce et prononcée, ainsi qu’une production accrue des marqueurs pro-inflammatoires par les cellules de la microglie durant la période néonatale et postnatale. Cette réponse pro-inflammatoire a été chronique puisqu’elle a été à nouveau détectée même à un âge avancé (âges adulte et moyen). Nos résultats mettraient en évidence l’activation et la polarisation des cellules de la microglie depuis la naissance, chez les animaux exposés, vers le phénotype M1, susceptible d’induire les effets neurotoxiques apparus beaucoup plus tard dans les stades de la vie. En effet, un comportement dépressif-like a été observé à l’âge adulte uniquement chez les mâles. Cette altération sexe dépendante du comportement de résignation a été attribuée à l’hyperactivation de l’axe de stress, l’axe hypothalamique pituitaire surrénalien, mise en évidence par une forte production de la corticostérone chez les mâles à l’âge adulte. Chez les femelles, nous avons mis en évidence le développement d’un comportement hyperactif dès l’âge adulte, et d’un déclin cognitif à l’âge moyen. Nos résultats suggèrent que le déficit de la mémoire de rétention des femelles d’âge moyen exposées périnatalement à des anguilles moyennement et hautement contaminées serait lié à la diminution significative de l’activation à la fois d’ERK ½ et du NF-κB ainsi qu’à la réduction significative du taux d’acétylcholine, détectées au niveau de l’hippocampe de ces souris. A partir de ces données et de celles obtenues par d’autres membres de notre équipe, il apparait de plus en plus pertinent de prendre en considération le risque du couplage des effets neuro-oxydatif et neuro-inflammatoire dans la genèse de nombreux troubles cognitifs et comportementaux surtout de manière tardive et irréversible. Cela pourrait également être à l’origine d’une fragilité et d’une imprégnation précoce de différentes populations cellulaires qui conduiraient tardivement à une dégénérescence précoce des cellules en particulier au niveau neuronal et glial. En conclusion, nos résultats suggèrent une programmation périnatale sexe-dépendante des troubles, mis en évidence aussi bien sur le plan comportemental que sur le plan cognitif chez les souris dont leurs mères ont consommé de l’anguille polluée, via des mécanismes inflammatoires. Cela laisse supposer un impact endocrino-dépendant dont il faudrait confirmer la réalité et les mécanismes / Several lines of evidence indicate that early-life inflammation may predispose to mental illness in later-life. In our study, we investigated the impact of perinatal exposure to polluted eels on the brain and microglia inflammation in a lifespan approach as well as on the resignation behavior, the locomotor activity and the cognitive performances in the later life of male and female offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Our results showed a chronic brain inflammation in male and female offspring mice compared to controls, as assessed at the birth, up weaning, adulthood and middle-age. Activated microglia produced pro-inflammatory markers across the lifespan of male as well as female exposed offspring. The plasmatic level of myeloperoxidase was found to be significantly higher in both adult and middle-aged males and females vs. control offspring. However, high corticosterone levels were only found in adult male offspring mice perinatally exposed to polluted eels, suggesting a sex-selective dysregulation of the adult hypothalamic- pituitary- adrenal (HPA) axis. Sex selective differences were also found in adulthood, with regard to the offspring resignation behavior. Indeed, depressive-like symptoms were only found in adult male mice perinatally exposed to polluted eels. On the middle- age, sexe selective effects were found with regard to memory and locomotor activity. Indeed, hyperactive phenotype was only detected in females. In addition, impaired long-term memory was only detected in middle-aged females, perinatally exposed to either intermediately or highly polluted eels. This deficit was related to decreases in ERK1/2 and p65 activation, and acetylcholine levels that were only detected in female hippocampus exposed to either intermediately or highly polluted eels. In conclusion, our results indicated that early-life inflammatory insults were the plausible causative factor that programmed the behavior impairments and cognitive deficit in the later-life of offspring, and suggested that sex played an important role in the determination of nature of the appeared alterations