产前接触脂多糖会导致年龄增长的后代大鼠认知缺陷。

Prenatal exposure to lipopolysaccharide results in cognitive deficits in age-increasing offspring rats.

机构信息

Department of Pharmaceutics, Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.

出版信息

Neuroscience. 2010 Mar 31;166(3):763-70. doi: 10.1016/j.neuroscience.2010.01.006. Epub 2010 Jan 13.

Abstract

Studies have suggested that maternal infection/inflammation maybe a major risk factor for neurodevelopmental brain damage. In the present study, we evaluated the effects of prenatal exposure to a low level of inflammatory stimulation lipopolysaccharide (LPS) repeatedly on spatial learning and memory performances in rat offspring's lifetime. Sixteen pregnant Sprague-Dawley rats were randomly divided into two groups. The rats in the LPS group were treated i.p. with LPS (0.79 mg/kg) at gestation day 8, 10 and 12; meanwhile the rats in the control group were treated with saline. After delivery, the rat offspring at 3- (young), 10- (adult) and 20-mon-old (aged) were allocated. Spatial learning and memory abilities were tested by Morris water maze. The structure of hippocampal CA1 region was observed by light microscopy. The expression of synaptophysin (SYP) and glial fibrillary acidic protein (GFAP) in hippocampal CA1 region were measured by immunohistochemistry. Results showed that the rat offspring of LPS group needed longer escape latency and path-length in the Morris water maze and presented a significant neuron loss, decreased expression of SYP, increased expression of GFAP in CA1 region in histological studies. All these changes were more significant with the age increasing. These findings support the hypothesis that maternal systemic inflammation may alter the state of astrocytes in rat offspring for a long time, the alteration may affect neurons and synapse development in neural system, increase the neurons' vulnerability to environment especially as the age increasing, at last result in distinct learning and memory impairment.

摘要

研究表明,母体感染/炎症可能是神经发育性脑损伤的一个主要危险因素。在本研究中,我们评估了孕鼠反复暴露于低水平炎症刺激物脂多糖(LPS)对其后代终身空间学习和记忆能力的影响。16 只孕 Sprague-Dawley 大鼠随机分为两组。LPS 组在妊娠第 8、10 和 12 天经腹腔注射 LPS(0.79mg/kg);同时,对照组大鼠给予生理盐水处理。分娩后,将 3 月龄(幼年期)、10 月龄(成年期)和 20 月龄(老年期)的大鼠分为不同组。通过 Morris 水迷宫测试空间学习和记忆能力。通过光镜观察海马 CA1 区的结构。免疫组织化学法测量海马 CA1 区突触素(SYP)和胶质纤维酸性蛋白(GFAP)的表达。结果显示,LPS 组大鼠后代在 Morris 水迷宫中需要更长的逃避潜伏期和路径长度,并且在组织学研究中表现出明显的神经元丢失、SYP 表达减少、CA1 区 GFAP 表达增加。所有这些变化随着年龄的增长而更加显著。这些发现支持了母体全身炎症可能会改变大鼠后代星形胶质细胞状态的假说,这种改变可能会影响神经系统中的神经元和突触发育,增加神经元对环境的脆弱性,尤其是随着年龄的增长,最终导致明显的学习和记忆障碍。

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