title: Perinatal programming of depressive-like behavior by inflammation in adult offspring mice whose mothers were fed polluted eels: Gender selective effects.
abstract: Several lines of evidence indicate that early-life inflammation may predispose to mental illness, including depression, in later-life. We investigated the impact of perinatal exposure to polluted eels on neonatal, postnatal, and adult brain inflammation, and on the resignation behavior of male and female adult offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Brain inflammatory markers including cytokines were assessed in offspring mice on the day of birth (i.e., on the postnatal day-PND 1), upon weaning (PND 21) and at adulthood (PND 100). Plasma myeloperoxidase and corticosterone levels were evaluated at PND 100. Immobility behavior of offspring was assessed in adulthood (i.e., at PNDs 95-100), using the tail suspension and forced swimming tests. Chronic brain inflammation was found in male and female offspring mice compared to controls, as assessed at PNDs 1, 21, and 100. The level of myeloperoxidase was found to be significantly higher in both adult males and females vs. control offspring. However, high corticosterone levels were only found in male offspring mice that were perinatally exposed to eels, suggesting a gender-selective dysregulation of the adult hypothalamic-pituitaryadrenal (HPA) axis. Gender-specific differences were also detected in adulthood in regard to offspring resignation behavior. Thus, compared to controls, males, but not females, whose mothers were fed eels during pregnancy and lactation exhibited a depressive-like behavior in adult age in both behavioral models of depression. Depressive symptoms were more pronounced in male mice perinatally exposed to either intermediate or highly polluted eels than those exposed to only lowly polluted eels. Our results indicate that early-life inflammatory insult is a plausible causative factor that induces the depressive phenotype exhibited by male adult offspring mice, most likely through a gender-specific HPA axis enhanced activation.
authors.affiliation: Université de Lorraine, Neurotoxicologie Alimentaire et Bioactivité, BP 4102, 57040 Metz, France.
authors.forename: Nidhal
authors.initials: N
authors.lastname: Soualeh
authors.affiliation: Université de Lorraine, Neurotoxicologie Alimentaire et Bioactivité, BP 4102, 57040 Metz, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Dridi
authors.affiliation: Université de Liège, Inorganic Analytical Chemistry, CART (Center for Analytical and Research Technology), B-4000 Sart-Tilman, Belgium.
authors.forename: Gauthier
authors.initials: G
authors.lastname: Eppe
authors.affiliation: Université de Lorraine, Neurotoxicologie Alimentaire et Bioactivité, BP 4102, 57040 Metz, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Némos
authors.affiliation: Université de Lorraine, Neurotoxicologie Alimentaire et Bioactivité, BP 4102, 57040 Metz, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Soulimani
authors.affiliation: Université de Lorraine, Neurotoxicologie Alimentaire et Bioactivité, BP 4102, 57040 Metz, France. Electronic address: jaouad.bouayed@univ-lorraine.fr.
authors.forename: Jaouad
authors.initials: J
authors.lastname: Bouayed
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D001921:Brain; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000235:genetics / Q000276:immunology; D003866:Depressive Disorder / Q000235:genetics / Q000276:immunology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007249:Inflammation; D051379:Mice; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D003345:Corticosterone
keywords: Depressive-like behavior; Early-life exposure; HPA axis; Inflammation; Later-life; Maternal diet; Polluted eels