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.
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; Instituto Nacional de Ciência e Tecnologia em Doenças Cerebrais, Excitotoxicidade e Neuroproteção, Porto Alegre, RS, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2020 Aug;234:108772. doi: 10.1016/j.cbpc.2020.108772. Epub 2020 Apr 27.
Long-term treatment with 3-nitropropionic acid (3-NPA), a toxin derived from plants and fungi, may reproduce symptoms and biochemical characteristics of Huntington's disease (HD). Our study evaluated the effects of 3-NPA on the physiological and behavioral responses in zebrafish larvae and adults. Larvae exposed to 0.1, 0.2, or 0.5 mM 3-NPA exhibited an increase in heart rate at 2- and 5-days post-fertilization (dpf). There was a decrease in the ocular distance at 5 dpf with 0.05 mM 3-NPA treatment. However, 3-NPA did not alter larval locomotor parameters. Adult zebrafish received 3-NPA intraperitoneal injections (a total of seven injections at doses 10, 20, or 60 mg/kg every 96 h) and showed a decrease in body weight , locomotion and aggressive behavior. No changes were observed in anxiety-like behavior and social interaction between 3-NPA-exposed animals and control groups. However, 3-NPA-treated animals (at 60 mg/kg) demonstrated impaired long-term aversive memory. Overall, 3-NPA exposure induced morphological and heart rate alterations in zebrafish larvae. Additionally, our study showed behavioral changes in zebrafish that were submitted to long-term 3-NPA treatment, which could be related to HD symptoms.
长期用 3-硝基丙酸（3-NPA）治疗，一种源自植物和真菌的毒素，可能会复制亨廷顿病（HD）的症状和生化特征。我们的研究评估了 3-NPA 对斑马鱼幼虫和成年鱼生理和行为反应的影响。暴露于 0.1、0.2 或 0.5 mM 3-NPA 的幼虫在受精后 2 天和 5 天（dpf）时心率增加。用 0.05 mM 3-NPA 处理时，在 5 dpf 时眼距减小。然而，3-NPA 并未改变幼虫的运动参数。成年斑马鱼接受 3-NPA 腹腔注射（总共 7 次注射，剂量为 10、20 或 60 mg/kg，每 96 小时一次），体重、运动和攻击行为下降。在焦虑样行为和 3-NPA 暴露动物与对照组之间的社交互动方面没有观察到变化。然而，用 3-NPA 处理的动物（60 mg/kg）表现出长期厌恶记忆受损。总的来说，3-NPA 暴露导致斑马鱼幼虫的形态和心率改变。此外，我们的研究表明，长期接受 3-NPA 治疗的斑马鱼出现了行为变化，这可能与 HD 症状有关。
