Abstract :
[en] Deficits in learning, memory and cognitive functions have been reported in humans as well as rodents following gestational and lactational exposure to polychlorinated biphenyls (PCBs), a family of persistent endocrine disrupting chemicals (EDCs) used for their insulating properties. As immature neurons are developing, they could represent a population of cells particularly sensitive to alterations caused by external factors such as EDCs. Moreover, those newborn neurons are important for cognitive functions and learning. For those reasons, we hypothesized that PCBs could alter the formation and development of two main populations of neurons: The granule cells in the dentate gyrus and the excitatory projection neurons in the cortex with an emphasis on the first population. Excitatory cortical projection neurons are produced in the ventricular zone of the wall of the lateral ventricle during gestation. The dentate gyrus originates from the dentate neuroepithelium and develops during the end of gestation and early postnatal period in rodents. After this developmental period, progenitor cells will be restricted to the subgranular zone of the dentate gyrus and continue to produce newborn neurons even in adults. The purpose of this thesis was to evaluate the effects of gestational or gestational and lactational exposure to Aroclor 1254, a commercial mixture of PCBs on neurogenesis.Regarding the hippocampus, which represents the main part of this manuscript, both the early postnatal period (corresponding to the peak of neurogenesis in the hippocampus) and adult neurogenesis have been investigated. Exposure to A1254 did not affect the number of newborn granule cells during the early postnatal period but abolished the developmental increase of spontaneous excitatory postsynaptic current frequency observed in control animals. Moreover, on the last day of the exposure (postnatal day 21), 1308 genes were differentially expressed in immature neurons of the dentate gyrus of exposed mice compared to control mice. Synaptic and mitochondrial genes were particularly sensitive to Aroclor 1254 exposure. Lipid peroxidation, a marker of oxidative stress, was increased in the subgranular zone of the dentate gyrus. In adult mice the number of immature neurons was moderately but significantly reduced by exposure to Aroclor 1254 during gestation and lactation but not by exposure during adulthood. During cortical development, Aroclor 1254 increased cell cycle exit and delayed radial neuronal migration. Those results suggest that exposure to Aroclor 1254 during brain development has moderate but significant effects on cortical and hippocampal neurogenesis and a combination of those alterations could possibly explain the behavioral deficits reported in the literature.
