斑马鱼幼体的昼夜节律运动行为受到文拉法辛的影响

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-06-14 DOI:10.1111/jpi.12984
W. Andrew Thompson, Mathilakath M. Vijayan
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引用次数: 0

摘要

抗抑郁药文拉法辛(一种选择性血清素和去甲肾上腺素再摄取抑制剂)是治疗重度抑郁症的常用处方药,在水生环境中的浓度很高。这种非靶向药物接触引起了人们对水生生物健康的关注。例如,我们曾证实,暴露于文拉法辛会扰乱斑马鱼(Danio rerio)的神经发育,导致行为改变。我们还观察到松果体和剑突中的血清素表达受到干扰,而松果体和剑突是调节昼夜节律的关键区域,因此我们推测暴露于文拉法辛的子代会干扰幼体斑马鱼的昼夜节律。为了验证这一假设,我们给斑马鱼胚胎注射了文拉法辛(1 或 10 纳克),并记录了 5 天大幼体在 24 小时内的运动活动。在昼夜周期的光照阶段,文拉法辛的沉积降低了幼体的运动活动,但在黑暗阶段却没有降低。黑暗期的褪黑激素水平高于光照期,但这并不受胚胎期文拉法辛沉积的影响。暴露于文拉法辛也不会影响时钟基因的转录本丰度,包括clock1a、bmal2、cry1a和per2,这些基因表现出明显的昼夜节律性。一个值得注意的发现是,暴露于褪黑激素受体拮抗剂卢吲哚会降低对照组在光照下的运动活性,而文拉法辛沉积胚胎培育的幼虫的运动活性更高。总之,卵子期暴露于文拉法辛会扰乱斑马鱼幼鱼在白天的运动活动,这表明抗抑郁药有能力扰乱行为的昼夜节律。我们的研究结果表明,褪黑激素信号的中断可能是文拉法辛影响昼夜节律行为的原因之一,但要阐明斑马鱼幼体的可能机制还需要进一步的研究。
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Zygotic Exposure to Venlafaxine Disrupts the Circadian Locomotor Activity Behaviour in Zebrafish Larvae

The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at high concentrations in the aquatic environment. Concerns have been raised related to the health of aquatic organisms in response to this nontargeted pharmaceutical exposure. For instance, we previously demonstrated that exposure to venlafaxine perturbs neurodevelopment, leading to behavioural alterations in zebrafish (Danio rerio). We also observed disruption in serotonin expression in the pineal and raphe, regions critical in regulating circadian rhythms, leading us to hypothesize that zygotic exposure to venlafaxine disrupts the circadian locomotor rhythm in larval zebrafish. To test this, we microinjected zebrafish embryos with venlafaxine (1 or 10 ng) and recorded the locomotor activity in 5-day-old larvae over a 24-h period. Venlafaxine deposition reduced larval locomotor activity during the light phase, but not during the dark phase of the diurnal cycle. The melatonin levels were higher in the dark compared to during the light photoperiod and this was not affected by embryonic venlafaxine deposition. Venlafaxine exposure also did not affect the transcript abundance of clock genes, including clock1a, bmal2, cry1a and per2, which showed a clear day/night rhythmicity. A notable finding was that exposure to luzindole, a melatonin receptor antagonist, decreased the locomotor activity in the control group in light, whereas the activity was higher in larvae raised from the venlafaxine-deposited embryos. Overall, zygotic exposure to venlafaxine disrupts the locomotor activity of larval zebrafish fish during the day, demonstrating the capacity of antidepressants to disrupt the circadian rhythms in behaviour. Our results suggest that disruption in melatonin signalling may be playing a role in the venlafaxine impact on circadian behaviour, but further investigation is required to elucidate the possible mechanisms in larval zebrafish.

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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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