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肠道细菌发酵产物丙酸的系统治疗以剂量依赖的方式降低大鼠的听觉惊吓反应幅度:对 ASD 啮齿动物模型的贡献。

Systemic Treatment with the Enteric Bacterial Fermentation Product, Propionic Acid, Reduces Acoustic Startle Response Magnitude in Rats in a Dose-Dependent Fashion: Contribution to a Rodent Model of ASD.

机构信息

Department of Psychology, Western University, London, Ontario, Canada.

Western University, London, Canada.

出版信息

Neurotox Res. 2019 Feb;35(2):353-359. doi: 10.1007/s12640-018-9960-9. Epub 2018 Sep 27.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by cognitive and sensorimotor deficits, among others. Hypo-sensitivity and hyper-sensitivity to different stimuli within the same sensory modality, a prominent symptom of ASD, can be assessed by acoustic startle response (ASR) and prepulse inhibition (PPI). Propionic acid (PPA) is a short-chain fatty acid and a by-product of the human gut microbiome. Rodents treated with PPA has been found to produce ASD-related behavioral abnormalities, gastrointestinal discomfort, and conditioned aversions. The present study examined ASR and PPI in adult male rats treated systemically (intraperitoneal injections) with two different doses of PPA. A single injection of PPA produced significant dose-dependent reductions in startle response magnitude relative to control rats. However, PPA-treated rats did not show significant sensorimotor gating abnormalities relative to controls, based on the PPI measures. These findings add to the growing body of evidence supporting the validity of the PPA rodent model of ASD.

摘要

自闭症谱系障碍(ASD)是一种神经发育障碍,其特征包括认知和感觉运动缺陷等。对同一感觉模式内不同刺激的低敏和高敏反应是 ASD 的一个突出症状,可以通过听觉惊跳反应(ASR)和前脉冲抑制(PPI)来评估。丙酸(PPA)是一种短链脂肪酸,也是人类肠道微生物组的副产品。研究发现,用 PPA 处理的啮齿动物会产生与 ASD 相关的行为异常、胃肠道不适和条件性厌恶。本研究在成年雄性大鼠中进行了系统(腹腔注射)给予两种不同剂量的 PPA,观察其对听觉惊跳反应(ASR)和前脉冲抑制(PPI)的影响。单次注射 PPA 会导致惊跳反应幅度相对于对照组显著降低,呈剂量依赖性。然而,根据 PPI 测量结果,PPA 处理组大鼠相对于对照组并未表现出明显的感觉运动门控异常。这些发现为 PPA 啮齿动物 ASD 模型的有效性提供了越来越多的证据支持。

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