Abstract

One of the most widespread experimental models for studying the development of autism spectrum disorders (ASDs) and methods of their therapy is the valproic acid-induced rodent model. Individuals born to females who received injections of valproic acid during pregnancy demonstrate a number of ASD-specific impairments. It was previously found that valproic acid affects neuromuscular transmission and, moreover, alters the expression of a set of genes during the development of neuromuscular junction. However, until recently it was unknown whether neuromuscular transmission changes in animals with fetal valproate syndrome and, if so, how? Using the “rotating rod” functional test, we found that in rats with a developed valproate syndrome, the coordination of movements did not differ from control animals. Using the methods of microelectrode electrophysiology, we analyzed (i) the amplitude-time parameters of single postsynaptic signals; (ii) the frequency of spontaneous release of acetylcholine quanta, (iii) the number of acetylcholine quanta released in response to the stimulus, (iv) the amplitude of evoked responses during rhythmic stimulation. We did not reveal any changes in the processes of acetylcholine release from the nerve ending and its reception on the muscle fiber membrane, both at rest and during nerve stimulation. Thus, it can be concluded that in rats with a developed fetal valproate syndrome, peripheral cholinergic neurotransmission does not undergo any functionally significant changes.

中文翻译：

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胎儿丙戊酸综合征大鼠外周胆碱能神经传递的功能评估

摘要

丙戊酸诱发的啮齿动物模型是研究自闭症谱系障碍（ASD）的发展及其治疗方法的最广泛的实验模型之一。孕期注射丙戊酸的女性所生的个体表现出许多ASD特异性损伤。先前已经发现丙戊酸影响神经肌肉的传递，而且在神经肌肉连接的发展过程中会改变一组基因的表达。但是，直到最近，尚不清楚胎儿丙戊酸综合征动物的神经肌肉传递是否发生变化，如果是，该如何变化？使用“旋转棒”功能测试，我们发现在患有丙戊酸盐综合征的大鼠中，运动的协调与对照组动物没有区别。使用微电极电生理学方法，我们分析（i）单个突触后信号的幅度-时间参数；（ii）乙酰胆碱量子自发释放的频率，（iii）响应刺激而释放的乙酰胆碱量子的数量，（iv）在有节奏的刺激过程中诱发反应的幅度。在静止和神经刺激过程中，我们没有揭示乙酰胆碱从神经末梢释放及其在肌纤维膜上的接受过程的任何变化。因此，可以得出结论，在患有胎儿丙戊酸综合征的大鼠中，外周胆碱能神经传递没有发生任何功能上的显着变化。（iii）响应刺激而释放的乙酰胆碱数量，（iv）在有节奏的刺激过程中诱发反应的幅度。在静止和神经刺激过程中，我们没有揭示乙酰胆碱从神经末梢释放及其在肌纤维膜上的接受过程的任何变化。因此，可以得出结论，在患有胎儿丙戊酸综合征的大鼠中，外周胆碱能神经传递没有发生任何功能上的显着变化。（iii）响应刺激而释放的乙酰胆碱数量，（iv）在有节奏的刺激过程中诱发反应的幅度。在静止和神经刺激过程中，我们没有揭示乙酰胆碱从神经末梢释放及其在肌纤维膜上的接受过程的任何变化。因此，可以得出结论，在患有胎儿丙戊酸综合征的大鼠中，外周胆碱能神经传递没有发生任何功能上的显着变化。