Laboratório de Neuroproteção e Doenças Metabólicas, 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.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Mar 30;36(2):258-63. doi: 10.1016/j.pnpbp.2011.10.002. Epub 2011 Oct 12.
Hyperprolinemia is an inherited disorder of proline metabolism and patients affected by this disease may present neurological manifestations, including seizures and cognitive dysfunctions. Moreover, an association between adulthood schizoaffective disorders and moderate hyperprolinemia has been reported. However, the mechanisms underlying these behavioral phenotypes still remain unclear. In the present study, we investigated the effect of proline treatments on behavioral parameters in zebrafish, such as locomotor activity, anxiety, and social interaction. Adult zebrafish (Danio rerio) were exposed to proline (1.5 and 3.0 mM) during 1h or 7 days (short- or long-term treatments, respectively). Short-term proline exposure did not promote significant changes on the behavioral parameters observed. Long-term exposure at 1.5 mM proline significantly increased the number of line crossing (47%), the total distance (29%), and the mean speed (33%) when compared to control group. A significant increase in the time spent in the upper portion of the test tank was also observed after this treatment (91%), which may be interpreted as an indicator of anxiolytic behavior. Proline at 1.5 mM also induced social interaction impairment (78%), when compared to the untreated group after long-term treatment. Moreover, these proline-induced behavioral changes in zebrafish were completely reversed by acute administration of an atypical antipsychotic drug (sulpiride), but not by a typical (haloperidol). These findings demonstrate that proline is able to induce schizophrenia-like symptoms in zebrafish, which reinforce the use of this species as a complementary vertebrate model for studying behavioral phenotypes associated with neurological dysfunctions characteristic of metabolic diseases.
高脯氨酸血症是一种脯氨酸代谢紊乱的遗传性疾病，受此疾病影响的患者可能会出现神经系统表现，包括癫痫发作和认知功能障碍。此外，已有报道称成年精神分裂情感障碍与中度高脯氨酸血症之间存在关联。然而，这些行为表型的潜在机制仍不清楚。在本研究中，我们研究了脯氨酸处理对斑马鱼行为参数的影响，例如运动活动、焦虑和社交互动。成年斑马鱼（Danio rerio）在 1 小时或 7 天（分别为短期或长期处理）内暴露于脯氨酸（1.5 和 3.0 mM）中。短期脯氨酸暴露不会对观察到的行为参数产生显著变化。与对照组相比，1.5 mM 脯氨酸的长期暴露显著增加了线交叉的次数（47%）、总距离（29%）和平均速度（33%）。经过这种处理后，还观察到测试箱上半部分的时间显著增加（91%），这可能被解释为焦虑行为的指标。与未经处理的组相比，1.5 mM 脯氨酸在长期处理后还诱导了社交互动障碍（78%）。此外，急性给予非典型抗精神病药物（舒必利）完全逆转了这些脯氨酸诱导的斑马鱼行为变化，但典型药物（氟哌啶醇）没有。这些发现表明，脯氨酸能够在斑马鱼中诱导出类似精神分裂症的症状，这加强了使用这种物种作为研究与代谢疾病相关的神经功能障碍特征相关的行为表型的补充脊椎动物模型。
