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Toxicité neuro-développementale d’une exposition gestationnelle à la pollution atmosphérique : effets à court et à long terme de l’inhalation répétée de particules de fumées de diesel chez le lapin

Abstract : Airborne pollution is a major public health concern. Among its components, the fine and ultrafine particles emitted by diesel engines are highly criticized. Indeed, these particles are able to gain the circulatory system to reach various organs and, in a certain degree, the brain. If their neurotoxicity is highly suspected in directly exposed populations, the consequences of maternal exposure on both fetal brain maturation and neurobehavioral development after birth remain poorly understood. Several recent studies conducted on humans or animal models have highlighted neurotoxic risks related to gestational exposure, due to the fragility of the brain at such critical period for its anatomic and functional development. Nevertheless, the consequences of maternal exposure on fetal brain maturation and neurobehavioral development after birth remain poorly understood in conditions of controlled and repeated low exposure. The aim of the thesis was to study the short- and long-term neurotoxic effects of gestational exposure to diesel engine fumes enriched with fine particles in conditions mimicking human exposure. The work was conducted in rabbit, because of its hemodichorial placentation which is anatomically and functionally close to that in humans. It focused on describing the damages to the anatomical and functional continuum between the olfactory system and the brain using behavioral, neurochemical and histological approaches in the late fetus and in adults. The results suggest the presence of chemically undefined nanosized particles in fetal olfactory tissues of exposed animals and a cellular disorganization of the same tissues, which is associated to localized neurochemical damage in the olfactory bulb and in several regions of the brain involved in dopaminergic and serotoninergic transmission, suggesting a denervation of centrifugal bulbar neuromodulatory systems from the central nervous system. At birth, a modulation in perinatal olfactory sensitivity in rabbits in response to the mammary pheromone, the perception of which is essential to trigger feeding behavior, is observed, suggesting a modification of the nervous networks of in utero exposed individuals. Neurochemical disturbances persist in adults, despite little impact on olfactory-based behaviors. Interestingly, a sex-dependent differential effect of this type of exposure on monoaminergic systems is observed in fetuses and adults. We propose that these neurodevelopmental perturbations of the anatomo-functional continuum between the olfactory system and the brain may indicate a neurotoxic potential and underline the need to further investigate its eventual link with the emergence of human neurodegenerative diseases. These data confirmed that prenatal phase should be considered as an important window for brain development, during which there is an elevated susceptibility to environmental insults.
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Estefanía Bernal-Meléndez. Toxicité neuro-développementale d’une exposition gestationnelle à la pollution atmosphérique : effets à court et à long terme de l’inhalation répétée de particules de fumées de diesel chez le lapin. Neurosciences [q-bio.NC]. Université de Lorraine, 2019. Français. ⟨NNT : 2019LORR0151⟩. ⟨tel-02516747⟩

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