Effets moléculaires de l'uranium appauvri chez un modèle de souris transgénique pour la maladie d'Alzheimer

Titre du congrès :International Congress of Toxicology Ville du congrès :Montréal Date du congrès :15/07/2007

It has been shown that ingestion of several heavy metals constitutes a risk factor in the development of Alzheimer disease (AD). The aim of this study was to determine if chronic contamination with depleted uranium (DU) could potentiate the development of AD. Transgenic Tg2576 mice were contaminated with DU during 8 months via drinking water (20 mg/L). Gene expression using real-time RT-PCR was performed for molecules implicated in amyloidogenesis (APP, BACE1 and ADAM10), neuroinflammation (IL 1béta, IL 6, TNF alpha, IL 10, TGF béta, NOS and IL 1ra), cholinergic system (AChE), as well as ApoE and tau protein. This gene study was completed by a histological study with visualization of brain senile plaques and immunostaining of astrocytes. Ingestion of DU modified gene expression of APP, BACE1 and ADAM10 ApoE, Tau and AChE. An anti-inflammatory process seemed to be detected at 8 months (IL 6: -50% and TNF-alpha: -35% with DU). These modifications were moderated and localized in specific brain structures, mainly in the frontal cortex and hypothalamus. The histological analysis did not reveal any change in astrocyte activation and senile plaque number between control and contaminated group. In conclusion, this study showed, for the first time, that chronic contamination with DU induce modifications of mRNA levels of molecules implicated in inflammation and neurodegeneration. However, these changes failed to increase AD development at the studied time as visualized by histology.