环境相关浓度的氟西汀和帕罗西汀对章鱼脑组织五羟色胺能系统的影响
Effects of Environmentally Relevant Concentrations of Fluoxetine and Paroxetine on Serotonergic Neurotransmitter Systems in Octopus Brain Tissue
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摘要: 近年来，随着抑郁症患者数量激增，抗抑郁性药物的使用量显著增加。由于药物具有特殊活性，常会对非目标生物的生理功能产生不良影响，干扰这些生物的生长发育，对其健康产生严重威胁。因此，本研究选取通过抑制五羟色胺(serotonin, 5-HT)转运体提高突触间隙5-HT水平发挥治疗作用的SSRI(selective serotonin reuptake inhibitor)类抗抑郁代表性药物氟西汀和帕罗西汀，探讨2种药物对章鱼脑组织5-HT能神经递质系统功能的影响。野生成体短蛸章鱼(O. ochellatus)于环境浓度的氟西汀、帕罗西汀溶液中连续暴露14 d，收集脑组织。通过qPCR和Western blot技术分析药物对章鱼脑组织5-HT能神经递质系统主要功能分子转录及表达水平的影响。结果显示，氟西汀和帕罗西汀引起章鱼脑组织中5-HT能系统重要功能分子转录及表达水平异常，表现为5-HTR1、5-HTR1B、5-HTR2A、SERT mRNA转录水平降低及5-HTR1、5-HTR1B、5-HTR2A、SERT蛋白表达水平升高，且具有药物特异性和剂量依赖性。此外，氟西汀与帕罗西汀混合暴露对章鱼脑5-HT能系统的影响程度弱于两者单独暴露，提示2种药物在干扰章鱼脑5-HT能系统正常功能过程中可能存在拮抗作用，通过比较二者的半衰期，认为氟西汀对于水生生态系统的影响更大。本研究结果表明，SSRI类抗抑郁药物氟西汀和帕罗西汀暴露可引起章鱼脑组织5-HT能神经系统主要功能分子转录与表达水平异常，可能干扰其正常功能，严重威胁章鱼健康。本研究为进一步研究抗抑郁症药物对章鱼神经系统的不良影响提供科学依据，为研究其他药物对海洋生物的健康损害效应提供参考。Abstract: In recent years, the use of antidepressants has increased significantly with the widespread epidemic of depression. Because of their special activity, they often have adverse effects on the physiological functions of non-target organisms, interfere with the growth and development of these organisms, and seriously threaten their health. Fluoxetine and paroxetine are the representative selective serotonin reuptake inhibitor (SSRI) antidepressants, which play a therapeutic role in improving the level of serotonin (5-HT) of the synaptic cleft by inhibiting the 5-HT transporter (SERT). In this study, we selected them to explore their effects on the function of 5-HT energy neurotransmitter system in the brain of octopus (O. ochellatus). Adult octopus were exposed to fluoxetine and paroxetine solutions for 14 d. And the brain tissues were collected after exposure. Quantitative RT-PCR (qPCR) and Western blot were applied to detect the main functional molecules of 5-HT neurotransmitter system, both gene and protein expression in octopus brain tissue. The results showed that fluoxetine and paroxetine induced abnormal transcription of the important functional molecules of 5-HT energy system in octopus brain tissue. The transcriptional expression levels of 5-HTR1、5-HTR1B、5-HTR2A, and SERT decreased, and the translational expression levels of 5-HTR1、5-HTR1B、5-HTR2A, and SERT increased with drug specificity and dose dependence. In addition, the effects of fluoxetine and paroxetine combined exposure on octopus brain 5-HT energy system were weaker than those of the two alone, suggesting that the two drugs might have antagonistic effects on the normal functioning of octopus brain 5-HT energy system. By comparing their half-life, we believed that fluoxetine had a greater impact on the aquatic ecosystem. Our results indicated that the exposure to fluoxetine and paroxetine could cause abnormal transcription of the main functional molecules of 5-HT energy nervous system in the octopus brain, leading to abnormal manifestations such as delayed physiological development and inhibition of feeding behavior of octopus, which seriously threatened its health. This study provided a scientific basis for further study of the adverse effects of antidepressants on the nervous system of octopus and a reference for the study of health damage effects of other drugs on marine organisms.
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Key words:
- fluoxetine /
- paroxetine /
- short-arm octopus /
- 5-HT neurotransmitter systems
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