Institut des Biomolécules Max Mousseron (IBMM), Unité Mixte de Recherches 5247 Centre National de la Recherche Scientifique-Université Montpellier 1-Université Montpellier 2, Montpellier, France.
Pediatr Res. 2013 Jun;73(6):750-5. doi: 10.1038/pr.2013.40. Epub 2013 Mar 11.
Prenatal infection is a major risk factor for the occurrence of neuropsychiatric disorders. These have been associated with hippocampal neuroanatomical and functional abnormalities. In the present study, we evaluated the occurrence of pyramidal cell disarray and reelin neuronal deficit in the hippocampus, and the protective role of N-acetyl-cysteine (NAC) in a rodent experimental model of prenatal immune challenge.
Sprague-Dawley rats received either 500 μg/kg of endotoxin (lipopolysaccharide, LPS) or 2 ml/kg of isotonic saline by i.p. injection on day 19 of gestation. After LPS injection, rats were or were not maintained on a preventive treatment of NAC (5 g/l in tap water), up to delivery. The pyramidal cell orientation and the number and type of reelin-expressing neurons were determined in male offspring.
Prenatal LPS challenge led to permanent pyramidal cell disarray and to an early and transient decreased density of reelin-immunoreactive neurons. These disorders, more pronounced in the CA3 area, were prevented by NAC.
Hippocampal cytoarchitectural alterations and reelin deficiency may be involved in the development of remote cognitive impairments in this model. The antioxidant NAC is an efficient neuroprotective drug that underlines the role of oxidative stress in prenatal infection and associated neurodevelopmental damage.
产前感染是神经精神疾病发生的主要危险因素。这些疾病与海马神经解剖和功能异常有关。在本研究中，我们评估了锥体神经元排列紊乱和 reelin 神经元缺失在海马中的发生情况，以及 N-乙酰半胱氨酸（NAC）在产前免疫挑战的啮齿动物实验模型中的保护作用。
妊娠第 19 天，Sprague-Dawley 大鼠通过腹腔注射接受 500μg/kg 的内毒素（脂多糖，LPS）或 2ml/kg 的等渗盐水。LPS 注射后，大鼠或不接受 NAC（自来水 5g/l）的预防治疗，直至分娩。在雄性后代中确定锥体神经元的取向以及 reelin 表达神经元的数量和类型。
产前 LPS 挑战导致永久性的锥体神经元排列紊乱，并导致 reelin 免疫反应性神经元的早期和短暂密度降低。这些在 CA3 区更为明显的紊乱，可通过 NAC 预防。
海马细胞构筑改变和 reelin 缺乏可能与该模型中远程认知障碍的发展有关。抗氧化剂 NAC 是一种有效的神经保护药物，强调了氧化应激在产前感染和相关神经发育损伤中的作用。
