Laboratório de Neuroproteção e Doenças Metabólicas, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.
Neuroscience. 2013 Oct 10;250:121-8. doi: 10.1016/j.neuroscience.2013.07.004. Epub 2013 Jul 16.
Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0mM) during 1h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 μM) were tested. Long-term proline exposures significantly increased AChE activity for both treated groups when compared to the control (34% and 39%). Moreover, the proline-induced increase on AChE activity was completely reverted by acute administration of antipsychotic drugs (haloperidol and sulpiride), as well as the changes induced in ache expression. When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism.
高脯氨酸血症是一种脯氨酸代谢紊乱的遗传性疾病，高脯氨酸血症患者可能出现神经系统表现，如癫痫发作、认知功能障碍和精神分裂情感障碍。然而，与这些症状相关的机制尚不清楚。在本研究中，我们评估了脯氨酸对斑马鱼大脑中乙酰胆碱酯酶（AChE）活性和基因表达的体内和体外影响。对于体内研究，动物在 1 小时或 7 天（分别为短期和长期处理）内暴露于两种脯氨酸浓度（1.5 和 3.0mM）下。对于体外测定，测试了不同的脯氨酸浓度（范围从 3.0 到 1000μM）。与对照组相比，长期脯氨酸暴露会显著增加两组的 AChE 活性（增加 34%和 39%）。此外，抗精神病药物（氟哌啶醇和舒必利）的急性给药以及 ache 表达的变化完全逆转了脯氨酸诱导的 AChE 活性增加。在体外评估时，脯氨酸不会引起 AChE 活性的显著变化。总之，这些数据表明，在成年斑马鱼中暴露于脯氨酸后，可能会改变负责控制乙酰胆碱水平的酶。这些发现有助于更好地理解高脯氨酸血症的病理生理学，并可能加强使用斑马鱼作为研究氨基酸代谢先天错误的补充脊椎动物模型。
