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经多脑室(ICV)内注射肠道细菌代谢产物丙酸处理的成年大鼠空间认知障碍及 1 周无处理后的恢复:对 ASD 啮齿动物模型的贡献。

Impaired Spatial Cognition in Adult Rats Treated with Multiple Intracerebroventricular (ICV) Infusions of the Enteric Bacterial Metabolite, Propionic Acid, and Return to Baseline After 1 Week of No Treatment: Contribution to a Rodent Model of ASD.

机构信息

Graduate Program in Neuroscience, Western University, London, Ontario, Canada.

The Kilee Patchell-Evans Autism Research Group, Department of Psychology, Western University, London, Ontario, Canada.

出版信息

Neurotox Res. 2019 May;35(4):823-837. doi: 10.1007/s12640-019-0002-z. Epub 2019 Mar 8.

DOI:10.1007/s12640-019-0002-z
PMID:30848474
Abstract

Propionic acid (PPA) is a dietary short chain fatty acid and an enteric bacterial metabolite. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioral changes similar to those seen in autism spectrum disorders (ASD), including perseveration. The effects of ICV infusions of PPA on spatial cognition were examined by giving rats infusions of either PPA (0.26 M, pH 7.4, 4 μl/infusion) or phosphate-buffered saline (PBS, 0.1 M) twice a day for 7 days. The rats were then tested in the Morris water maze (MWM) for acquisition of spatial learning. After a recovery period of 1 week of no treatment, the rats were then tested for reversal of spatial learning in the MWM. PPA-treated rats showed impaired spatial learning in the maze, relative to controls, as demonstrated by increased search latencies, fewer direct and circle swims, and more time spent in the periphery of the maze than PBS controls. After a recovery period of 1 week of no treatment, these animals exhibited normal spatial reversal learning indicating that the behavioral cognitive deficits caused by PPA seem to be reversible.

摘要

丙酸(PPA)是一种膳食短链脂肪酸和肠道细菌代谢物。在啮齿动物中,脑室内(ICV)输注 PPA 已被证明会产生类似于自闭症谱系障碍(ASD)的行为改变,包括坚持。通过每天两次给大鼠输注 PPA(0.26 M,pH 7.4,4 μl/输注)或磷酸盐缓冲盐水(PBS,0.1 M),检查了 ICV 输注 PPA 对空间认知的影响,持续 7 天。然后,大鼠在 Morris 水迷宫(MWM)中接受空间学习的测试。经过 1 周无治疗的恢复期后,大鼠在 MWM 中接受空间学习的逆转测试。与对照组相比,PPA 处理的大鼠在迷宫中表现出空间学习受损,表现为搜索潜伏期增加、直接游泳和圆形游泳次数减少,以及在迷宫外围停留的时间增加。经过 1 周无治疗的恢复期后,这些动物表现出正常的空间反转学习,表明 PPA 引起的行为认知缺陷似乎是可逆的。

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Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: Contribution to a rodent model of autism spectrum disorder.系统给予肠道细菌代谢产物丙酸治疗会导致幼年大鼠社会行为减少:对自闭症谱系障碍啮齿动物模型的贡献。
Dev Psychobiol. 2019 Jul;61(5):688-699. doi: 10.1002/dev.21825. Epub 2019 Jan 28.
2
Lipopolysaccharide (LPS) induced sickness in early adolescence alters the behavioral effects of the short-chain fatty acid, propionic acid, in late adolescence and adulthood: Examining anxiety and startle reactivity.脂多糖(LPS)在青春期早期引起的疾病会改变短链脂肪酸丙酸在青春期后期和成年期的行为效应:考察焦虑和惊吓反应。
Behav Brain Res. 2019 Mar 15;360:312-322. doi: 10.1016/j.bbr.2018.12.003. Epub 2018 Dec 3.
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PI3K/AKT/mTOR 信号通路抑制剂大黄素可改善成年大鼠丙酸诱导自闭症模型的神经行为和神经化学缺陷。
Metab Brain Dis. 2022 Aug;37(6):1909-1929. doi: 10.1007/s11011-022-01026-0. Epub 2022 Jun 10.
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Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats.新型生物素对丙酸诱导的大鼠自闭症特征的治疗作用。
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