Programa de Pós-Graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Laboratório de Neuroquímica e Psicofarmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Mol Neurobiol. 2020 Aug;57(8):3485-3497. doi: 10.1007/s12035-020-01970-x. Epub 2020 Jun 12.
Methionine (Met) has important functions for homeostasis of various species, including zebrafish. However, the increased levels of this amino acid in plasma, a condition known as hypermethioninemia, can lead to cell alterations. Met is crucial for the methylation process and its excesses interfere with the cell cycle, an effect that persists even after the removal of this amino acid. Some conditions may lead to a transient increase of this amino acid with unexplored persistent effects of Met exposure. In the present study, we investigated the behavioral and neurochemical effects after the withdrawal of Met exposure. Zebrafish were divided into two groups: control and Met-treated group (3 mM) for 7 days and after maintained for 8 days in tanks containing only water. In the eighth day post-exposure, we evaluated locomotion, anxiety, aggression, social interaction, and memory, as well as oxidative stress parameters, amino acid, and neurotransmitter levels in the zebrafish brain. Our results showed that 8 days after Met exposure, the treated group showed decreased locomotion and aggressive responses, as well as impaired aversive memory. The Met withdrawal did not change thiobarbituric acid reactive substances, reactive oxygen species, and nitrite levels; however, we observed a decrease in antioxidant enzymes superoxide dismutase, catalase, and total thiols. Epinephrine and cysteine levels were decreased after the Met withdrawal whereas carnitine and creatine levels were elevated. Our findings indicate that a transient increase in Met causes persistent neurotoxicity, observed by behavioral and cognitive changes after Met withdrawal and that the mechanisms underlying these effects are related to changes in antioxidant system, amino acid, and neurotransmitter levels.
蛋氨酸（Met）对各种物种的内稳态具有重要功能，包括斑马鱼。然而，血浆中这种氨基酸水平的升高，即高蛋氨酸血症，会导致细胞改变。Met 对甲基化过程至关重要，其过量会干扰细胞周期，即使在去除这种氨基酸后，这种效应仍会持续存在。一些情况可能导致这种氨基酸的短暂增加，而 Met 暴露的持续影响仍未被探索。在本研究中，我们研究了停止 Met 暴露后的行为和神经化学效应。将斑马鱼分为两组：对照组和 Met 处理组（3mM），持续 7 天，然后在仅含有水的水箱中维持 8 天。在暴露后第 8 天，我们评估了运动、焦虑、攻击、社交互动和记忆，以及斑马鱼大脑中的氧化应激参数、氨基酸和神经递质水平。我们的结果表明，Met 暴露 8 天后，处理组表现出运动和攻击反应减少，以及厌恶记忆受损。Met 戒断并未改变硫代巴比妥酸反应物质、活性氧和亚硝酸盐水平；然而，我们观察到抗氧化酶超氧化物歧化酶、过氧化氢酶和总巯基的减少。Met 戒断后肾上腺素和半胱氨酸水平降低，而肉碱和肌酸水平升高。我们的发现表明，Met 的短暂增加会导致持久的神经毒性，在 Met 戒断后通过行为和认知变化观察到，这些效应的机制与抗氧化系统、氨基酸和神经递质水平的变化有关。
