title: Neurodevelopmental damage after prenatal infection: role of oxidative stress in the fetal brain.
abstract: Prenatal infection is a major risk responsible for the occurrence of psychiatric conditions in infants. Mimicking maternal infection by exposing pregnant rodents to bacterial endotoxin lipopolysaccharide (LPS) also leads to major brain disorders in the offspring. The mechanisms of LPS action remain, however, unknown. Here, we show that LPS injection during pregnancy in rats, 2 days before delivery, triggered an oxidative stress in the hippocampus of male fetuses, evidenced by a rapid rise in protein carbonylation and by decreases in alpha-tocopherol levels and in the ratio of reduced/oxidized forms of glutathione (GSH/GSSG). Neither protein carbonylation increase nor decreases in alpha-tocopherol levels and GSH/GSSG ratio were observed in female fetuses. NMDA synaptic currents and long-term potentiation in CA1, as well as spatial recognition in the water maze, were also impaired in male but not in female 28-day-old offspring. Pretreatment with the antioxidant N-acetylcysteine prevented the LPS-induced changes in the biochemical markers of oxidative stress in male fetuses, and the delayed detrimental effects in male 28-day-old offspring, completely restoring both long-term potentiation in the hippocampus and spatial recognition performance. Oxidative stress in the hippocampus of male fetuses may thus participate in the neurodevelopmental damage induced by a prenatal LPS challenge.
authors: Oxidative Stress and Neuroprotection, IBMM, CNRS UMR-5247, University of Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 5, France.
authors: Fabien
authors: F
authors: Lanté
authors: Johann
authors: J
authors: Meunier
authors: Janique
authors: J
authors: Guiramand
authors: Tangui
authors: T
authors: Maurice
authors: Mélanie
authors: M
authors: Cavalier
authors: Marie-Céleste
authors: MC
authors: de Jesus Ferreira
authors: Rose
authors: R
authors: Aimar
authors: Catherine
authors: C
authors: Cohen-Solal
authors: Michel
authors: M
authors: Vignes
authors: Gérard
authors: G
authors: Barbanel
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D001927:Brain Diseases / Q000139:chemically induced / Q000196:embryology / Q000209:etiology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000503:physiopathology; D007239:Infections / Q000196:embryology*; D008070:Lipopolysaccharides / Q000633:toxicity; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D005978:Glutathione; D024502:alpha-Tocopherol; D019803:Glutathione Disulfide