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妊娠前接触 会产生识别胎儿大脑模拟表位的母体抗体,并导致后代出现神经化学和行为功能障碍。

Pregestational Exposure to Produces Maternal Antibodies That Recognize Fetal Brain Mimotopes and Induces Neurochemical and Behavioral Dysfunction in the Offspring.

机构信息

Posgrado en Ciencias Biológicas y de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico.

Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez", Mexico City 14269, Mexico.

出版信息

Cells. 2022 Nov 29;11(23):3819. doi: 10.3390/cells11233819.

Abstract

The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels of IgG anti- from mothers and their neonates, with a higher risk of developing schizophrenia. The absence of the parasite and the levels of IgGs found in the early stages of life suggest a transplacental transfer of the anti- IgG antibodies, which could bind fetal brain structures by molecular mimicry and induce alterations in neurodevelopment. This study aimed to determine the maternal pathogenic antibodies formation that led to behavioral impairment on the progeny of rats immunized with . Female rats were immunized prior to gestation with lysate (3 times/once per week). The anti- IgG levels were determined in the serum of pregestational exposed females' previous mating. After this, locomotor activity, cognitive and social tests were performed. Cortical neurotransmitter levels for dopamine and glutamate were evaluated at 60 PND in the progeny of rats immunized before gestation (Pregestational group). The maternal pathogenic antibodies were evidenced by their binding to fetal brain mimotopes in the Pregestational group and the reactivity of the serum containing anti- IgG was tested in control fetal brains (non-immunized). These results showed that the Pregestational group presented impairment in short and long-term memory, hypoactivity and alteration in social behavior, which was also associated with a decrease in cortical glutamate and dopamine levels. We also found the IgG antibodies bound to brain mimotopes in fetuses from females immunized with , as well as observing a strong reactivity of the serum females immunized for fetal brain structures of fetuses from unimmunized mothers. Our results suggest that the exposure to before gestation produced maternal pathogenic antibodies that can recognize fetal brain mimotopes and lead to neurochemical and behavioral alterations in the offspring.

摘要

母体免疫系统在产前感染时的激活被认为是后代发生精神疾病的风险因素。弓形体病是与精神分裂症相关的致病感染之一。最近的研究表明,母体和其新生儿的 IgG 抗- 水平之间存在关联,并且发生精神分裂症的风险更高。寄生虫的缺失和生命早期发现的 IgG 水平表明,抗- IgG 抗体通过胎盘转移,这些抗体可能通过分子模拟结合胎儿大脑结构,并诱导神经发育改变。本研究旨在确定导致用弓形体病免疫的大鼠后代出现行为障碍的母体致病抗体的形成。在妊娠前,用弓形体病裂解物(3 次/每周一次)对雌性大鼠进行免疫。在之前的交配中,检测妊娠前暴露的雌性血清中的抗- IgG 水平。在此之后,进行运动活动、认知和社交测试。在妊娠前免疫的大鼠后代(妊娠前组)中,于 60 天龄时评估皮质神经递质多巴胺和谷氨酸水平。在妊娠前组中,通过其与胎儿大脑模拟表位的结合证明了母体致病抗体的存在,并且还测试了含有抗- IgG 的血清在对照胎儿大脑(未免疫)中的反应性。这些结果表明,妊娠前组表现出短期和长期记忆损伤、活动减少和社会行为改变,这也与皮质谷氨酸和多巴胺水平降低有关。我们还发现 IgG 抗体与弓形体病免疫雌性的胎儿大脑模拟表位结合,并且还观察到来自未免疫母亲的胎儿的未免疫雌性血清对胎儿大脑结构具有强烈的反应性。我们的结果表明,在妊娠前暴露于弓形体病会产生可识别胎儿大脑模拟表位的母体致病抗体,并导致后代的神经化学和行为改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/580e/9741080/11d3e2d6d199/cells-11-03819-g001.jpg

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