da Silva Lemos Isabela, Wessler Leticia Burato, Duarte Mariane Bernardo, da Silva Guilherme Lodetti, Bernardo Henrique Teza, Candiotto Gabriela, Torres Carolina Antunes, Petronilho Fabricia, Rico Eduardo Pacheco, Streck Emilio Luiz
Laboratório de Doenças Neurometabólicas, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brasil.
Laboratório de Psiquiatria Translacional, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brasil.
Metab Brain Dis. 2022 Dec;37(8):2925-2935. doi: 10.1007/s11011-022-01070-w. Epub 2022 Aug 30.
Maple Syrup Urine Disease (MSUD) is a metabolic disorder characterized by high levels in blood and urine of branched-chain amino acids leucine, isoleucine, and valine and their alpha-ketoacids, by a partial or total blockade in the activity of branched-chain complex alpha-keto acids dehydrogenase. The main symptoms in MSUD occur in the central nervous system, including cognitive deficits, locomotor, poor feeding, seizures, psychomotor delay, and mental retardation, but the mechanisms of neurotoxicity and behavior alteration due to this disease are poorly understood, thus this study aimed at showing the effects of leucine exposure on glutamate levels and behavior in zebrafish. For this, we analyzed the behavior using the social preference test and novel object recognition test, moreover, we analyse the glutamate levels and uptake using scintillation and high-performance liquid chromatography methods. Our results demonstrated a decrease in glutamate levels and uptake, accompanied by memory and social impairment. In conclusion, these results suggest that alterations in glutamate levels can be associated with behavior impairment, however, more studies are necessary to understand the mechanisms for brain damage in MSUD.
枫糖尿症（MSUD）是一种代谢紊乱疾病，其特征是血液和尿液中支链氨基酸亮氨酸、异亮氨酸和缬氨酸及其α-酮酸水平升高，以及支链复合α-酮酸脱氢酶活性部分或完全受阻。MSUD的主要症状出现在中枢神经系统，包括认知缺陷、运动障碍、喂养困难、癫痫发作、精神运动发育迟缓以及智力低下，但这种疾病导致神经毒性和行为改变的机制尚不清楚，因此本研究旨在展示亮氨酸暴露对斑马鱼谷氨酸水平和行为的影响。为此，我们使用社交偏好测试和新物体识别测试分析行为，此外，我们使用闪烁法和高效液相色谱法分析谷氨酸水平和摄取情况。我们的结果表明谷氨酸水平和摄取减少，同时伴有记忆和社交障碍。总之，这些结果表明谷氨酸水平的改变可能与行为障碍有关，然而，需要更多的研究来了解MSUD中脑损伤的机制。
