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产前脂多糖暴露致母体免疫激活导致雄性 Wistar 大鼠出现持久的自闭症样社交、认知和免疫改变。

Maternal Immune Activation Induced by Prenatal Lipopolysaccharide Exposure Leads to Long-Lasting Autistic-like Social, Cognitive and Immune Alterations in Male Wistar Rats.

机构信息

Section of Biomedical Sciences and Technologies, Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146 Rome, Italy.

Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.

出版信息

Int J Mol Sci. 2023 Feb 15;24(4):3920. doi: 10.3390/ijms24043920.

Abstract

Several studies have supported the association between maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of gestation and an increased susceptibility to the development of various psychiatric and neurological disorders, including autism and other neurodevelopmental disorders (NDDs), in the offspring. In the present work, we aimed to provide extensive characterization of the short- and long-term consequences of MIA in the offspring, both at the behavioral and immunological level. To this end, we exposed Wistar rat dams to Lipopolysaccharide and tested the infant, adolescent and adult offspring across several behavioral domains relevant to human psychopathological traits. Furthermore, we also measured plasmatic inflammatory markers both at adolescence and adulthood. Our results support the hypothesis of a deleterious impact of MIA on the neurobehavioral development of the offspring: we found deficits in the communicative, social and cognitive domains, together with stereotypic-like behaviors and an altered inflammatory profile at the systemic level. Although the precise mechanisms underlying the role of neuroinflammatory states in neurodevelopment need to be clarified, this study contributes to a better understanding of the impact of MIA on the risk of developing behavioral deficits and psychiatric illness in the offspring.

摘要

几项研究支持了母体免疫激活(MIA)与后代各种精神和神经疾病(包括自闭症和其他神经发育障碍(NDD))易感性增加之间的关联,这种激活是由妊娠关键期暴露于病原体或炎症引起的。在目前的工作中,我们旨在从行为和免疫水平两个方面广泛描述 MIA 对子代的短期和长期后果。为此,我们用脂多糖(Lipopolysaccharide)处理 Wistar 孕鼠,并在婴儿期、青少年期和成年期对后代进行与人类精神病理学特征相关的多个行为领域的测试。此外,我们还在青少年期和成年期测量了血浆炎症标志物。我们的结果支持 MIA 对后代神经行为发育有不良影响的假说:我们发现,在交流、社交和认知领域存在缺陷,同时还存在刻板样行为和全身炎症特征改变。尽管需要阐明神经炎症状态在神经发育中的作用的具体机制,但这项研究有助于更好地理解 MIA 对后代行为缺陷和精神疾病风险的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e951/9968168/d4f919bfff38/ijms-24-03920-g001.jpg

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