Simvastatin (SIM), a hypocholesterolaemic drug belonging to the statins group, is a widely prescribed pharmaceutical for prevention of cardiovascular diseases. Several studies showed that lipophilic statins, as SIM, cross the blood-brain barrier and interfere with the energy metabolism of the central nervous system in humans and mammalian models. In fish and other aquatic organisms, the effects of SIM on the brain energy metabolism are unknown, particularly following exposure to low environmentally relevant concentrations. Therefore, the present study aimed at investigating the influence of SIM on gene signaling pathways involved in brain energy metabolism of adult zebrafish (Danio rerio) following chronic exposure (90 days) to environmentally relevant SIM concentrations ranging from 8 ng/L to 1000 ng/L. Real-time PCR was used to determine the transcript levels of several genes involved in different pathways of the brain energy metabolism (glut1b, gapdh, acadm, accα, fasn, idh3a, cox4i1, and cox5aa). The findings here reported integrated well with ecological and biochemical responses obtained in a parallel study. Data demonstrated that SIM modulates transcription of key genes involved in the mitochondrial electron transport chain, in glucose transport and metabolism, in fatty acid synthesis and β-oxidation. Further, SIM exposure led to a sex-dependent transcription profile for some of the studied genes. Overall, the present study demonstrated, for the first time, that SIM modulates gene regulation of key pathways involved in the energy metabolism in fish brain at environmentally relevant concentrations.

中文翻译：

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长期暴露于环境相关水平的辛伐他汀会破坏参与能量代谢的斑马鱼脑基因信号传导。

辛伐他汀（SIM）是他汀类药物的降胆固醇药，是预防心血管疾病的广泛处方药物。多项研究表明，亲脂性他汀类药物（SIM）可以穿越血脑屏障，并干扰人类和哺乳动物模型中中枢神经系统的能量代谢。在鱼类和其他水生生物中，SIM对脑能量代谢的影响尚不清楚，尤其是在暴露于低环境相关浓度后。因此，本研究旨在调查SIM对成年斑马鱼（Danio rerio）大脑暴露于环境相关的SIM浓度范围从8 ng / L至1000 ng / L的脑能量代谢所涉及的基因信号通路的影响。 L. 实时荧光定量PCR用于确定参与脑能量代谢不同途径的几种基因（glut1b，gapdh，acadm，accα，fasn，idh3a，cox4i1和cox5aa）的转录水平。此处的研究结果表明，该研究与平行研究中获得的生态和生化反应很好地结合在一起。数据表明，SIM调节了线粒体电子转运链，葡萄糖转运和代谢，脂肪酸合成和β-氧化中涉及的关键基因的转录。此外，SIM暴露导致某些研究基因的性别依赖性转录谱。总的来说，本研究首次证明了SIM在环境相关浓度下调节鱼脑能量代谢所涉及的关键途径的基因调控。