Neurodevelopmental damage after prenatal infection:: Role of oxidative stress in the fetal brain
Neurodevelopmental damage after prenatal infection:: Role of oxidative stress in the fetal brain
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DOI：
10.1016/j.freeradbiomed.2007.01.027
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发表时间：
2007-04-15
影响因子：
7.4
通讯作者：
Barbanel, Gerard
中科院分区：
文献类型：
--
作者：
Lante, Fabien;Meunier, Johann;Barbanel, Gerard
产前感染是导致婴儿出现精神疾病的主要危险因素。通过将怀孕的啮齿动物暴露于细菌内毒素脂多糖（LPS）中来模拟母体感染也会导致后代出现严重的脑部疾病。然而，脂多糖的作用机制尚不清楚。在这里，我们发现在大鼠怀孕期间，在分娩前2天注射LPS，引发了雄性胎儿海马的氧化应激，证据是蛋白质羰基化迅速上升，a-生育酚水平下降，谷胱甘肽（GSH/GSSG）还原/氧化形式的比例下降。在雌性胎儿中，蛋白质羰基化既没有增加也没有减少α -生育酚水平和GSH/GSSG比值。雄性小鼠的NMDA突触电流和CA1的长时程增强以及水迷宫的空间识别功能也受到损害，但雌性小鼠没有受到损害。用抗氧化剂n -乙酰半胱氨酸预处理可以阻止lps诱导的雄性胎儿氧化应激生化标志物的变化，并延缓28日龄雄性后代的有害影响，完全恢复海马的长期增强和空间识别能力。因此，雄性胎儿海马中的氧化应激可能参与了产前LPS刺激引起的神经发育损伤。(c) 2007爱思唯尔公司版权所有。
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 a-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. (c) 2007 Elsevier Inc. All rights reserved.