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Theses

TOXICITE NEURO-DEVELOPPEMENTALE D’UNE EXPOSITION GESTATIONNELLE A LA POLLUTION ATMOSPHERIQUE. EFFETS A COURT ET A LONG TERME DE L’INHALATION REPETEE DE PARTICULES DE FUMEES DE DIESEL CHEZ LE LAPIN.

Abstract : Airborne pollution, especially from diesel exhaust, is a major public health concern. Several epidemiological studies make it responsible for the premature death of tens of thousands of individuals per year. Apart from its impact on the respiratory and cardiovascular systems, it is also pointed at increasing neurological diseases in adults. 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, funded by ADEME as part of the ANSES BrainAirPoll project (EST 2014/1/190), 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 closer to that in humans than that in rodents. 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 for triggering feeding behavior, is observed, suggesting a modification of the nervous networks of individuals born to exposed dams. Neurochemical disturbances persist in adults, despite little impact on olfactory-based behaviors. Interestingly, a sex-dependent differential effect of exposure to filtered diesel engine exhaust 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 to be confirmed and underline the need to further investigate the 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. Preventing exposure of pregnant woman to a polluted environment should, therefore, be considered by public authorities.
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https://hal.inrae.fr/tel-03338392
Contributor : Christine Baly <>
Submitted on : Wednesday, September 8, 2021 - 3:43:29 PM
Last modification on : Friday, September 10, 2021 - 3:32:58 AM

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  • HAL Id : tel-03338392, version 1

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Christine Baly, Estefanía Bernal-Meléndez, Henri Schroeder. TOXICITE NEURO-DEVELOPPEMENTALE D’UNE EXPOSITION GESTATIONNELLE A LA POLLUTION ATMOSPHERIQUE. EFFETS A COURT ET A LONG TERME DE L’INHALATION REPETEE DE PARTICULES DE FUMEES DE DIESEL CHEZ LE LAPIN.. Sciences du Vivant [q-bio]. Université Paris-Saclay, 2019. Français. ⟨tel-03338392⟩

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