Rahmati-Holasoo Hooman, Salek Maghsoudi Armin, Akbarzade Milad, Gholami Mahdi, Shadboorestan Amir, Vakhshiteh Faezeh, Armandeh Maryam, Hassani Shokoufeh
Department of Aquatic Animal Health, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Center of Excellence for Warm Water Fish Health and Disease, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Iran J Basic Med Sci. 2023 Mar;26(3):316-325. doi: 10.22038/IJBMS.2023.68165.14889.
Autism is a complicated neurodevelopmental disorder characterized by social interaction deficiencies, hyperactivity, anxiety, communication disorders, and a limited range of interests. The zebrafish () is a social vertebrate used as a biomedical research model to understand social behavior mechanisms.
After spawning, the eggs were exposed to sodium valproate for 48 hr, after which the eggs were divided into eight groups. Except for the positive and control groups, there were six treatment groups based on oxytocin concentration (25, 50, and 100 μM) and time point (24 and 48 hr). Treatment was performed on days 6 and 7, examined by labeling oxytocin with fluorescein-5-isothiocyanate (FITC) and imaging with confocal microscopy and the expression levels of potential genes associated with the qPCR technique. Behavioral studies, including light-dark background preference test, shoaling behavior, mirror test, and social preference, were performed on 10, 11, 12, and 13 days post fertilization (dpf), respectively.
The results showed that the most significant effect of oxytocin was at the concentration of 50 μM and the time point of 48 hr. Increased expression of , , and genes was also significant at this oxytocin concentration. Light-dark background preference results showed that oxytocin in the concentration of 50 µM significantly increased the number of crosses between dark and light areas compared with valproic acid (positive group). Also, oxytocin showed an increase in the frequency and time of contact between the two larvae. We showed a decrease in the distance in the larval group and an increase in time spent at a distance of one centimeter from the mirror.
Our findings showed that the increased gene expression of , , and improved autistic behavior. Based on this study some indications showed that oxytocin administration in the larval stage could significantly improve the autism-like spectrum.
自闭症是一种复杂的神经发育障碍,其特征为社交互动缺陷、多动、焦虑、沟通障碍以及兴趣范围有限。斑马鱼是一种社会性脊椎动物,被用作生物医学研究模型以了解社会行为机制。
产卵后,将鱼卵暴露于丙戊酸钠中48小时,之后将鱼卵分为八组。除阳性组和对照组外,基于催产素浓度(25、50和100 μM)和时间点(24和48小时)有六个处理组。在第6天和第7天进行处理,通过用异硫氰酸荧光素(FITC)标记催产素并用共聚焦显微镜成像以及使用qPCR技术检测相关潜在基因的表达水平来进行检测。分别在受精后第10、11、12和13天进行行为学研究,包括明暗背景偏好试验、群居行为、镜像试验和社交偏好试验。
结果表明,催产素的最显著作用出现在浓度为50 μM和时间点为48小时时。在该催产素浓度下, 、 和 基因的表达增加也很显著。明暗背景偏好结果显示,与丙戊酸(阳性组)相比,50 μM浓度的催产素显著增加了明暗区域之间的穿越次数。此外,催产素显示出两个幼虫之间接触频率和时间的增加。我们发现幼虫组之间的距离减小,并且在距离镜子一厘米处停留的时间增加。
我们的研究结果表明, 、 和 基因表达的增加改善了自闭症行为。基于这项研究,一些迹象表明在幼虫阶段给予催产素可以显著改善自闭症谱系症状。