Evaluation of neuroinflammatory effects of perinatal exposure to contaminated eels (Anguilla anguilla L.) by persistent organic pollutants on behavior and cognitive functions using a mouse model

• Main Author: Soualeh, Nidhal
• Other Authors: Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Université de Lorraine, Rachid Soulimani, Jaouad Bouayed
• Format: Doctoral or Postdoctoral Thesis
• Language: French
• Published: HAL CCSD 2017
• Subjects: Cognitive deficit; Depressive-like behavior; Early-life exposure; HPA axis; Hyperactivity; Inflammation; Later-life; Long-term memory; Maternal diet; Microglia; Perinatal programming; Polluted eels; Sex effect; Age; Anguilles polluées; Axe HPA; Comportement; Déficit mnésique; Effet dépressif-like; Effet Sexe; Hyperactivité; Exposition périnatale; Mémoire à long terme; Microglie; Programmation périnatale; [SDV.EE.SANT]Life Sciences [q-bio]/Ecology; environment/Health; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Anguilla anguilla
• Online Access: https://theses.hal.science/tel-01810227; https://theses.hal.science/tel-01810227/document; https://theses.hal.science/tel-01810227/file/DDOC_T_2017_0288_SOUALEH.pdf

Several lines of evidence indicate that early-life inflammation may predispose to mental illness in later-life. In our study, we investigated the impact of perinatal exposure to polluted eels on the brain and microglia inflammation in a lifespan approach as well as on the resignation behavior, the locomotor activity and the cognitive performances in the later life of male and female offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Our results showed a chronic brain inflammation in male and female offspring mice compared to controls, as assessed at the birth, up weaning, adulthood and middle-age. Activated microglia produced pro-inflammatory markers across the lifespan of male as well as female exposed offspring. The plasmatic level of myeloperoxidase was found to be significantly higher in both adult and middle-aged males and females vs. control offspring. However, high corticosterone levels were only found in adult male offspring mice perinatally exposed to polluted eels, suggesting a sex-selective dysregulation of the adult hypothalamic- pituitary- adrenal (HPA) axis. Sex selective differences were also found in adulthood, with regard to the offspring resignation behavior. Indeed, depressive-like symptoms were only found in adult male mice perinatally exposed to polluted eels. On the middle- age, sexe selective effects were found with regard to memory and locomotor activity. Indeed, hyperactive phenotype was only detected in females. In addition, impaired long-term memory was only detected in middle-aged females, perinatally exposed to either intermediately or highly polluted eels. This deficit was related to decreases in ERK1/2 and p65 activation, and acetylcholine levels that were only detected in female hippocampus exposed to either intermediately or highly polluted eels. In conclusion, our results indicated that early-life inflammatory insults were the plausible causative factor that programmed ...