Institute for Environmental Assessment and Water Research (IDAEA-CSIC), 08034 Barcelona, Spain.
Department of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià, Universitat Ramon Llull, 08017 Barcelona, Spain.
Int J Mol Sci. 2024 Jul 13;25(14):7688. doi: 10.3390/ijms25147688.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交互动和沟通障碍、焦虑、多动以及对特定主题的兴趣受限。除了遗传因素外，多种环境因素与 ASD 的发展有关。动物模型可以作为理解 ASD 复杂性的重要工具。在这项研究中，通过在受精后 4 至 48 小时内用丙戊酸（VPA）处理胚胎，在鱼水中饲养至成年阶段，在斑马鱼中开发了一种 ASD 的化学模型。这是第一次采用行为分析和神经递质谱综合方法，用于确定早期暴露于 VPA 对幼虫和成年阶段的影响。来自 VPA 处理胚胎的幼虫表现出过度活跃和视觉及振动逃避反应减少，以及神经递质谱改变，谷氨酸水平升高，乙酰胆碱和去甲肾上腺素水平降低。来自 VPA 处理胚胎的成年斑马鱼表现出社交行为受损，表现为更大的鱼群大小和对同种斑马鱼的兴趣降低。神经递质分析显示大脑中的多巴胺和 GABA 水平显著降低。这些结果支持该模型在 ASD 研究中的潜在预测有效性。
