School of Natural Sciences and Medicine, Ilia State University, 3/5 K. Cholokashvili venue, 0162 Tbilisi, Georgia; Department of Brain Ultrastructure and Nanoarchitecture. I. Beritashvili Center of Experimental Biomedicine. 14 Gotua Street, 0160 Tbilisi, Georgia.
School of Natural Sciences and Medicine, Ilia State University, 3/5 K. Cholokashvili venue, 0162 Tbilisi, Georgia; Department of Brain Ultrastructure and Nanoarchitecture. I. Beritashvili Center of Experimental Biomedicine. 14 Gotua Street, 0160 Tbilisi, Georgia.
Micron. 2019 Oct;125:102732. doi: 10.1016/j.micron.2019.102732. Epub 2019 Aug 6.
Autism spectrum disorder is a group of life-long developmental syndromes, characterized by stereotypic behavior, restricted, communication deficits, cognitive and social impairments. Autism spectrum disorder is heritable state, provided by the mutations of well-conserved genes; however, it has been increasingly accepted, that most of such states are the result of complex interaction between individual's genetic profile and the environment that he/she is exposed to. Gut microbiota plays one of the central roles in the etiology of autism. Propionic acid is one of the most abundant short-chain fatty acids, made by enteric bacteria. Propionic acid has many positive functions and acts as the main mediator between nutrition, gut microbiota and brain physiology. However, increased level of propionic acid is associated with various neurological pathologies, including autism. It is proposed that some types of autism might be partially related with alterations in propionic acid metabolism. The amygdala, the main component of social brain, via its large interconnections with fronto-limbic neural system, plays one of the key roles in social communications, emotional memory and emotional processing. Social behavior is a hot topic in autism research. As to anxiety, it is not the main characteristics of ASD, but represents one of the most common its co morbidities. Several theoretical reasons compatible with amygdala dysfunction have been suggested to account for socio-emotional disturbances in autism. In the present study, using adolescent male Wistar rats, the effect of acute administration of low dose of propionic acid on social behavior, anxiety-like behavior and the structure/ultrastructure of central nucleus of amygdale was described. In addition to qualitative analysis, on electron microscopic level the quantitative analysis of some parameters of synapses was performed. Behavior was assessed 2, 24 and 48 hours after treatment. The results revealed that even single and relatively low dose of propionic acid is sufficient to produce fast and relatively long lasting (48 h after treatment) decrease of social motivation, whereas asocial motivation and emotional sphere remain unaffected. Morphological analyses of propionic acid-treated brain revealed the reduced neuron number and the increase of the number of glial cells. Electron microscopically, in some neurons the signs of apoptosis and chromatolysis were detected. Glial alterations were more common. Particularly, the activation of astrocytes and microglia were often observed. Pericapillary glia was the most changed. Neuronal, glial and presynaptic mitochondria showed substantial structural diversities, mainly in terms of size and form. Total number of the area of presynaptic profile was significantly decreased. Some axons were moderately demyelinated. In general, the data indicate that even low dose of propionic acid produces in adolescent rodents immediate changes in social behavior, and structural/ultrastructural alterations in amygdala. Ultrastructural alterations may reflect moderate modifications in functional networks of social brain.
自闭症谱系障碍是一组终身发育障碍，其特征为刻板行为、受限的交流障碍、认知和社会障碍。自闭症谱系障碍是一种遗传性疾病，由高度保守基因的突变引起；然而，越来越多的人认为，这种状态大多是个体遗传特征与他/她所接触的环境之间复杂相互作用的结果。肠道微生物群在自闭症的发病机制中起着核心作用之一。丙酸是最丰富的短链脂肪酸之一，由肠道细菌产生。丙酸具有许多积极的功能，是营养、肠道微生物群和大脑生理学之间的主要调节剂。然而，丙酸水平升高与包括自闭症在内的各种神经病理学有关。有人提出，某些类型的自闭症可能与丙酸代谢的改变部分相关。杏仁核是社交大脑的主要组成部分，通过其与额-边缘神经系统的大量相互连接，在社交交流、情绪记忆和情绪处理中发挥关键作用。社交行为是自闭症研究的一个热门话题。至于焦虑，它不是 ASD 的主要特征，但代表了其最常见的合并症之一。为了说明自闭症中的社交-情感障碍，已经提出了几个与杏仁核功能障碍兼容的理论原因。在本研究中，使用青春期雄性 Wistar 大鼠，描述了低剂量丙酸急性给药对社交行为、焦虑样行为和中央杏仁核核的结构/超微结构的影响。除了定性分析外，还在电子显微镜水平上对突触的一些参数进行了定量分析。行为评估在治疗后 2、24 和 48 小时进行。结果表明，即使是单次和相对低剂量的丙酸也足以产生快速且相对持久的（治疗后 48 小时）社交动机下降，而社交动机和情绪领域不受影响。丙酸处理后的大脑形态学分析显示神经元数量减少，神经胶质细胞数量增加。电镜下，一些神经元出现凋亡和色氨酸溶解的迹象。神经胶质改变更为常见。特别是，经常观察到星形胶质细胞和小胶质细胞的激活。血管周围胶质是变化最大的。神经元、神经胶质和突触前线粒体表现出显著的结构多样性，主要表现在大小和形态上。突触前轮廓区域的总面积显著减少。一些轴突中度脱髓鞘。总的来说，数据表明，即使是低剂量的丙酸也会在青春期啮齿动物中立即引起社交行为的变化，并导致杏仁核的结构/超微结构改变。超微结构改变可能反映了社交大脑功能网络的适度改变。
