胎儿酒精谱系障碍模型改变成年斑马鱼谷氨酸能神经传递的功能

Fetal alcohol spectrum disorders model alters the functionality of glutamatergic neurotransmission in adult zebrafish

Keywords：Alcohol; Brain; FASD; Glutamate; Glutamatergic neurotransmission; Zebrafish
关键词：酒精; 脑; FASD； 谷氨酸； 谷氨酸能神经传递； 斑马鱼

非哺乳动物：鱼类
作者：Baggio S, Zenki K, Martins Silva A, Dos Santos TG, Rech G, Lazzarotto G, Dias RD, Mussulini BH, Rico EP, de Oliveira DL 
出版期刊：《NEUROTOXICOLOGY》 2020/3/12

Abstract：

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.

文章摘要：

胎儿酒精谱系障碍 (FASD) 描述了广泛的乙醇引起的发育障碍，包括颅面畸形、神经化学和行为障碍。斑马鱼已成为一种流行的动物模型，用于评估严重和轻度 FASD 的长期影响，包括神经传递的改变。谷氨酸是乙醇引起的发育障碍中受影响最大的神经递质系统之一。因此，本研究的目的是评估成年斑马鱼 FASD 模型中谷氨酸能神经递质系统的功能。斑马鱼幼虫（受精后 24 小时）暴露于乙醇（0.1%、0.25%、0.5% 和 1%）2 小时。 4个月后，将动物安乐死并取出它们的大脑。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​​吸测量。胚胎乙醇暴露减少了斑马鱼大脑中 Na+ 依赖性谷氨酸的摄取。这种减少受到头孢曲松治疗的积极调节，头孢曲松是一种促进谷氨酸转运蛋白 EAAT2 表达的β-内酰胺抗生素。此外，0.5% 和 1% 乙醇组在成年期表现出谷氨酸与脑膜的结合减少和 Na+/K+ ATP 酶活性降低。此外，乙醇降低了 1% EtOH 组中的谷氨酰胺合成酶活性。胚胎乙醇暴露不会改变谷氨酸囊泡转运蛋白 VGLUT2 的免疫含量和成年期大脑的线粒体能量代谢。我们的研究结果表明，胚胎乙醇暴露可能会导致成年斑马鱼大脑中谷氨酸能神经传递的显着改变。

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