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产前脂多糖诱导下丘脑多巴胺能活性低下和自闭症样行为:重复性自我梳理和刻板行为。

Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies.

作者信息

Kirsten Thiago B, Bernardi Maria M

机构信息

Department of Pathology, School of Veterinary Medicine, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo, SP, 05508-270, Brazil; Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP, 04026-002, Brazil.

Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP, 04026-002, Brazil.

出版信息

Behav Brain Res. 2017 Jul 28;331:25-29. doi: 10.1016/j.bbr.2017.05.013. Epub 2017 May 16.

Abstract

Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces social, cognitive, and communication deficits. For a complete screening of autistic-like behaviors, the objective of this study was to evaluate if our rat model also induces restricted and repetitive stereotyped behaviors. Thus, we studied the self-grooming microstructure. We also studied the neurochemistry of hypothalamus and frontal cortex, which are brain areas related to autism to better understand central mechanisms involved in our model. Prenatal LPS exposure on gestational day 9.5 increased the head washing episodes (frequency and time), as well as the total self-grooming. However, body grooming, paw/leg licking, tail/genital grooming, and circling behavior/tail chasing did not vary significantly among the groups. Moreover, prenatal LPS induced dopaminergic hypoactivity (HVA metabolite and turnover) in the hypothalamus. Therefore, our rat model induced restricted and repetitive stereotyped behaviors and the other main symptoms of autism experimentally studied in rodent models and also found in patients. The hypothalamic dopaminergic impairments seem to be associated with the autistic-like behaviors.

摘要

我们小组之前的研究表明,孕期暴露于脂多糖(LPS)可诱发社交、认知和沟通缺陷,脂多糖可模拟革兰氏阴性菌感染。为了全面筛查自闭症样行为,本研究的目的是评估我们的大鼠模型是否也会诱发受限和重复的刻板行为。因此,我们研究了自我梳理行为的微观结构。我们还研究了下丘脑和额叶皮质的神经化学,这两个脑区与自闭症有关,以便更好地了解我们模型中涉及的中枢机制。孕期第9.5天暴露于脂多糖会增加头部清洗次数(频率和时间)以及总的自我梳理行为。然而,身体梳理、舔爪/腿、舔尾/生殖器以及转圈行为/追尾巴在各组之间没有显著差异。此外,孕期暴露于脂多糖会导致下丘脑多巴胺能活性降低(高香草酸代谢物和周转率)。因此,我们的大鼠模型诱发了受限和重复的刻板行为以及在啮齿动物模型中进行实验研究且在患者中也存在的自闭症其他主要症状。下丘脑多巴胺能损伤似乎与自闭症样行为有关。

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