Laboratory of Cellular Neurochemistry, Programa De Pós-graduação Em Ciências Biológicas: Bioquímica, Departamento De Bioquímica, Instituto De Ciências Básicas Da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil.
Laboratory of Cellular Neurochemistry, Programa De Pós-graduação Em Ciências Biológicas: Bioquímica, Departamento De Bioquímica, Instituto De Ciências Básicas Da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil.
Neurotoxicology. 2020 May;78:152-160. doi: 10.1016/j.neuro.2020.03.003. Epub 2020 Mar 12.
Fetal alcohol spectrum disorders (FASD) describe a wide range of ethanol-induced developmental disabilities, including craniofacial dysmorphology, and neurochemical and behavioral impairments. Zebrafish has become a popular animal model to evaluate the long-lasting effects of, both, severe and milder forms of FASD, including alterations to neurotransmission. Glutamate is one of the most affected neurotransmitter systems in ethanol-induced developmental disabilities. Therefore, the aim of the present study was to evaluate the functionality of the glutamatergic neurotransmitter system in an adult zebrafish FASD model. Zebrafish larvae (24 h post-fertilization) were exposed to ethanol (0.1 %, 0.25 %, 0.5 %, and 1%) for 2 h. After 4 months, the animals were euthanized and their brains were removed. The following variables were measured: glutamate uptake, glutamate binding, glutamine synthetase activity, Na+/K + ATPase activity, and high-resolution respirometry. Embryonic ethanol exposure reduced Na+-dependent glutamate uptake in the zebrafish brain. This reduction was positively modulated by ceftriaxone treatment, a beta-lactam antibiotic that promotes the expression of the glutamate transporter EAAT2. Moreover, the 0.5 % and 1% ethanol groups demonstrated reduced glutamate binding to brain membranes and decreased Na+/K + ATPase activity in adulthood. In addition, ethanol reduced glutamine synthetase activity in the 1% EtOH group. Embryonic ethanol exposure did not alter the immunocontent of the glutamate vesicular transporter VGLUT2 and the mitochondrial energetic metabolism of the brain in adulthood. Our results suggest that embryonic ethanol exposure may cause significant alterations in glutamatergic neurotransmission in the adult zebrafish brain.
胎儿酒精谱系障碍（FASD）描述了一系列广泛的乙醇诱导的发育障碍，包括颅面畸形以及神经化学和行为损伤。斑马鱼已成为一种流行的动物模型，用于评估严重和较轻形式的 FASD 的长期影响，包括神经传递的改变。谷氨酸是乙醇诱导的发育障碍中受影响最严重的神经递质系统之一。因此，本研究旨在评估成年斑马鱼 FASD 模型中谷氨酸能神经递质系统的功能。将斑马鱼幼虫（受精后 24 小时）暴露于乙醇（0.1%、0.25%、0.5%和 1%）中 2 小时。4 个月后，处死动物并取出其大脑。测量了以下变量：谷氨酸摄取、谷氨酸结合、谷氨酰胺合成酶活性、Na+/K+ATP 酶活性和高分辨率呼吸测定。胚胎乙醇暴露降低了斑马鱼大脑中 Na+依赖性谷氨酸摄取。头孢曲松治疗可正向调节这种减少，头孢曲松是一种β-内酰胺抗生素，可促进谷氨酸转运体 EAAT2 的表达。此外，0.5%和 1%乙醇组在成年期表现出脑细胞膜谷氨酸结合减少和 Na+/K+ATP 酶活性降低。此外，乙醇降低了 1% EtOH 组的谷氨酰胺合成酶活性。胚胎乙醇暴露并未改变成年期脑内谷氨酸囊泡转运体 VGLUT2 的免疫含量和脑线粒体能量代谢。我们的结果表明，胚胎乙醇暴露可能导致成年斑马鱼大脑中谷氨酸能神经传递的显著改变。
