在发育过程中多巴胺的增加会导致斑马鱼幼鱼运动能力受损但不会引起焦虑样行为,这种损伤在后期阶段仍持续存在。

Impairment of motor but not anxiety-like behavior caused by the increase of dopamine during development is sustained in zebrafish larvae at later stages.

机构信息

Núcleo de Neurociências, Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Laboratório de Neurociências and Centro de Tecnologia em Medicina Molecular, Department of Mental Health, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

出版信息

Int J Dev Neurosci. 2020 Apr;80(2):106-122. doi: 10.1002/jdn.10009. Epub 2020 Feb 12.

Abstract

Many neuropsychiatric disorders are associated with both dopaminergic (DAergic) and developmental hypotheses. Since DAergic receptors are expressed in the developing brain, it is possible that alterations in dopamine (DA) signaling may impair brain development and consequent behavior. In our previous study, using a zebrafish model, we showed that an increase of DA during the 3 to 5 days postfertilization (dpf) developmental window (an important window for GABAergic neuronal differentiation) affects the motor behavior of 5 dpf larvae. In this study, we set out to determine whether these behavioral alterations were sustained in larvae at older stages (7 and 14 dpf). To test this hypothesis, we chronically treated zebrafish larvae from 3 to 5 dpf with DA. After washing the drug, we recorded and analyzed the first 5 and 30 min of the motor behavior of 5, 7, and 14 dpf subjects. We analyzed mobile episodes, distance traveled, time mobile, distance traveled per mobile episode, time in movement per mobile episode, and distance traveled per time mobile. We showed, once again, that an increase of DA during the 3 to 5 dpf developmental window reduces the number of movement episodes initiated by 5 dpf larvae. We also detected a decrease of other motor behavior parameters in 5 dpf DA-treated larvae. We observed that these alterations are sustained in the 7 dpf larvae. However, we did not see these general locomotor alterations in the 14 dpf larvae. Moreover, we detected a decrease of distance traveled and an increase of time of locomotion per episode in the first 5 min of behavioral analyses in 14 dpf DA-treated larvae. To test if the alterations in the first 5 min were due to anxiety-like behavior, we used a light/dark preference paradigm. We recorded 5dpf, 7dpf, and 14dpf larvae for 5 min and analyzed time of freezing, preference for light or dark, number of entries to the dark, percentage of time in the light. We observed that 5dpf larvae treated with DA showed more freezing, less passages to the dark, and more time spent in the light as compared to their control counterparts. But 7dpf and 14dpf larvae did not show these alterations. Taken overall, therefore, our results suggest that DA does play a role in the development of zebrafish motor behavior, and, furthermore, that some behaviors are more sensitive than others to the effects of DAergic imbalances during development.

摘要

许多神经精神疾病与多巴胺能(DAergic)和发育假说都有关联。由于 DA 受体在发育中的大脑中表达,因此多巴胺(DA)信号的改变可能会损害大脑发育和随后的行为。在我们之前的研究中,我们使用斑马鱼模型表明,在受精后 3 到 5 天(即 GABA 能神经元分化的重要窗口)的发育窗口中 DA 的增加会影响 5 天龄幼虫的运动行为。在这项研究中,我们着手确定这些行为改变是否在年龄较大的阶段(7 天龄和 14 天龄)的幼虫中持续存在。为了验证这一假设,我们从 3 天龄到 5 天龄用 DA 处理斑马鱼幼虫。在清洗药物后,我们记录和分析了 5 天龄、7 天龄和 14 天龄的幼虫的运动行为的前 5 分钟和 30 分钟。我们分析了运动发作、行进距离、运动时间、每次运动发作的行进距离、每次运动发作的运动时间和行进距离与运动时间的比值。我们再次表明,在 3 到 5 天龄的发育窗口中 DA 的增加会减少 5 天龄幼虫开始的运动发作次数。我们还检测到 5 天龄 DA 处理的幼虫的其他运动行为参数减少。我们观察到这些改变在 7 天龄幼虫中持续存在。然而,我们没有在 14 天龄幼虫中看到这些一般的运动改变。此外,我们在 14 天龄 DA 处理的幼虫的前 5 分钟的行为分析中发现了行进距离的减少和每次发作的运动时间的增加。为了测试前 5 分钟的改变是否由于类似焦虑的行为,我们使用了明暗偏好范式。我们记录了 5 天龄、7 天龄和 14 天龄的幼虫 5 分钟,并分析了冻结时间、对明暗的偏好、进入黑暗的次数、在亮处的时间百分比。我们观察到,与对照组相比,用 DA 处理的 5 天龄幼虫表现出更多的冻结、更少的进入黑暗和更多的在亮处的时间。但是,7 天龄和 14 天龄的幼虫没有表现出这些改变。因此,总的来说,我们的结果表明,DA 在斑马鱼运动行为的发育中确实发挥了作用,而且,有些行为比其他行为对发育过程中 DA 能失衡的影响更为敏感。

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