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百草枯诱导帕金森病模型大鼠迷走神经背核神经元基本膜特性的描述。

Characterization of the Basic Membrane Properties of Neurons of the Rat Dorsal Motor Nucleus of the Vagus in Paraquat-Induced Models of Parkinsonism.

机构信息

Department of Neural and Behavioral Sciences, Penn State - College of Medicine, Hershey, PA, United States of America.

Department of Neural and Behavioral Sciences, Penn State - College of Medicine, Hershey, PA, United States of America.

出版信息

Neuroscience. 2019 Oct 15;418:122-132. doi: 10.1016/j.neuroscience.2019.08.048. Epub 2019 Sep 3.

Abstract

Most of Parkinson's disease (PD) patients experience gastrointestinal dysfunctions, including gastric hypomotility. The dorsal motor nucleus of the vagus (DMV) modulates the motility of the upper gastrointestinal (GI) tract. Paraquat (P) administration induces Parkinsonism in experimental models, and we have developed recently an environmental model of Parkinsonism in which rats are treated with subthreshold doses of P and lectins (P + L), in both models rats develop reduced gastric motility prodromal to the full extent of motor deficits. The aim of the present study was to examine whether the membrane properties of DMV neurons in these two experimental models of Parkinsonism were altered. Whole cell recordings in slices containing DMV neurons were conducted in male Sprague Dawley rats which received either injections of paraquat (10 mg/kg i.p.; 10P), or oral administration of paraquat (1 mg/kg) and lectin (0.05% w/v; P + L). Morphological reconstructions of DMV neurons were conducted at the end of the recordings. The repolarization kinetics of the afterhyperpolarization phase of the action potential was accelerated in 10P neurons vs control, while the phase plot revealed a slower depolarizing slope. At baseline, the amplitude of miniature excitatory postsynaptic currents was increased in P + L neurons. No differences in the morphology of DMV neurons were observed. These data indicate that the membrane and synaptic properties of DMV neurons are altered in rodent models of Parkinsonism, in which neurons of 10P and P + L rats demonstrate an increased excitatory transmission, perhaps in an attempt to counteract the paraquat-induced gastric hypomotility.

摘要

大多数帕金森病(PD)患者都经历过胃肠道功能障碍,包括胃动力不足。迷走神经背核(DMV)调节上胃肠道(GI)的运动。百草枯(P)给药在实验模型中诱导帕金森病,我们最近开发了一种环境模型的帕金森病,其中大鼠用亚阈值剂量的 P 和凝集素(P+L)治疗,在这两种模型中,大鼠在运动缺陷完全出现之前胃动力就会降低。本研究的目的是检查这两种帕金森病实验模型中 DMV 神经元的膜特性是否发生改变。在接受百草枯(10mg/kg,腹腔内注射;10P)或百草枯(1mg/kg)和凝集素(0.05%w/v;P+L)口服给药的雄性 Sprague Dawley 大鼠的切片中进行含有 DMV 神经元的全细胞记录。在记录结束时对 DMV 神经元进行形态重建。与对照组相比,10P 神经元的动作电位后超极化期的复极化动力学加快,而相位图显示出较慢的去极化斜率。在基线时,P+L 神经元的微小兴奋性突触后电流的幅度增加。未观察到 DMV 神经元的形态差异。这些数据表明,在帕金森病的啮齿动物模型中,DMV 神经元的膜和突触特性发生了改变,其中 10P 和 P+L 大鼠的神经元表现出增强的兴奋性传递,这可能是为了对抗百草枯引起的胃动力不足。

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