Résumé:
Persistent organic pollutants (POPs) are long-lived organic compounds that are considered one of the major risks on ecosystem and human health. Mainly, POPs are known by induction of oxidative stress and mitochondrial dysfunction as well as disturbance of metabolism and endocrine disruption. Recently, great concerns have been raised about environmental exposure to POPs mixtures and its potential toxicity even that doses of exposure are largely below the estimated acceptable daily intake
(ADI). Neurotoxicity of POPs is one of the major concerns, since brain is mostly targeted by these lipophilic compounds because of its important contain in lipids and iron and its deficient antioxidant system. Neurodevelopmental toxicity is particularly considered, because POPs are able to cross placenta and breast milk, thus might interact with processes of neurodevelopment and maturation. Starting from these concepts, the present work aims to evaluate the neurotoxic effect of POPs at environmental doses from the perspective of three scenarios of exposure in rodents: exposure to an environmental POPs mixture on adulthood, neurodevelopmental exposure to an environmental POPs
mixture and the possible exposure to neurotoxic effects of POPs through the axis of a peripheral organ like the liver.
Chronic exposure to a representative environmental mixture of POPs composed of endosulfan (2.6 μg/kg), chlorpyrifos (5.2 μg/kg), naphthalene (0.023 μg/kg) and benzopyrene (0.002 μg/kg), induced in adult female rats memory and locomotor deficits as shown by behavioural tests like Morris water maze and the open field tests. Same exposure induced oxidative stress in mitochondria and cytosol as shown by an increase in lipid peroxidation and a perturbation in GSH levels and antioxidant enzymes
activity. Gestational and lactational exposure to the same mixture induced neurodevelopment deficits as shown by a decrease in body weight and the delay in the maturation of some primitive reflexes. In juvenile rats we noticed also locomotor and behavioural deficits as noted by the novel object recognition tests. We noticed as well a state of oxidative stress in both cytosol and mitochondria. In another context, perfluoroctane sulfonate (PFOS) is a neurotoxic and hepatotoxic POPs. Recent
reports revealed its potential modulation of Alzheimer disease (AD) biomarkers; however molecular mechanisms are still poorly understood. In the actual study chronic exposure to this compound (0, 0063 %) in adult mice induced a perturbation in Glycogen synthase kinase (GSK3B) and insulin degrading enzyme (IDE) levels in the brain as noticed by Western blot analysis. We noticed also a perturbation in other AD biomarkers like B Amyloid (AB) and Amyloid precursor protein (APP), total tau protein and it phosphorylated form. These effects are related to perturbation in lipid and glucose metabolism as shown by lipid and glucose blood concentration registered in the same cohort study.
As a conclusion we have shown that environmental exposure to POPs during development or in adult age could alter brain integrity. Such alterations might pave the way to the development of neurodegenerative diseases in the aging brain. In this context, further researches are required, to understand well patterns of brain response to environmental exposure to POPs and its implications in the aetiology of neurodegenerative diseases.
