It is well documented that propionic acid (PPA) produces behavioral, morphological, molecular and immune responses in rats that are characteristic of autism spectrum disorder in humans. However, whether PPA affects the ultrastructure and synaptic architecture of regions of autistic brain has not been adequately addressed. Earlier we show that single intraperitoneal (IP) injection of PPA (175 mg/kg) produces superficial changes in the spatial memory and learning of adolescent male Wistar rats. However, in neurons, synapses and glial cells of hippocampal CA1 area and medial prefrontal cortex transient (mainly) or enduring alterations were detected. In this study, we used electron microscopic morphometric analysis to test the effect of PPA on different structural parameters of axodendritic synapses of the hippocampus and prefrontal cortex. The animals were treated with a single IP injection of PPA (175 mg/kg). The length and width of synaptic active zone, the area of presynaptic and postsynaptic mitochondria, the distance between presynaptic mitochondria and the synapse active zone, the distance between postsynaptic mitochondria and postsynaptic density and the depth and opening diameter of neuronal porosome complex were evaluated. Our results show that synaptic mitochondria of the hippocampus and prefrontal cortex are the most vulnerable to PPA treatment: in both regions, the area of postsynaptic mitochondria were increased. In general, our results show that even small dose of PPA, which produces only superficial effects on spatial memory and learning is able to alter the synapse architecture in brain regions involved in cognition and autism pathogenesis. Therefore, the microbiome may be involved in the control of neurotransmission in these regions.

中文翻译：

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丙酸影响大鼠海马和前额皮质的突触结构

有充分证据表明，丙酸 (PPA) 会在大鼠体内产生行为、形态、分子和免疫反应，这些反应是人类自闭症谱系障碍的特征。然而，PPA 是否影响自闭症大脑区域的超微结构和突触结构尚未得到充分解决。早些时候我们表明，单次腹腔（IP）注射PPA（175 mg/kg）会对青春期雄性Wistar大鼠的空间记忆和学习产生表面变化。然而，在海马 CA1 区和内侧前额皮质的神经元、突触和神经胶质细胞中，检测到短暂（主要）或持久的改变。在本研究中，我们使用电子显微镜形态测量分析来测试PPA对海马和前额皮质轴突突触不同结构参数的影响。对动物进行单次腹膜内注射 PPA (175 mg/kg)。评估突触活性区的长度和宽度、突触前和突触后线粒体的面积、突触前线粒体与突触活性区之间的距离、突触后线粒体与突触后密度之间的距离以及神经元多孔体复合体的深度和开口直径。我们的结果表明，海马和前额皮质的突触线粒体最容易受到 PPA 治疗的影响：在这两个区域，突触后线粒体的面积都增加了。总的来说，我们的结果表明，即使是小剂量的 PPA（仅对空间记忆和学习产生表面影响）也能够改变参与认知和自闭症发病机制的大脑区域的突触结构。因此，微生物组可能参与这些区域神经传递的控制。