Julia Canzian , João V. Borba , Cássio M. Resmim , Khadija A. Mohammed , Camilla W. Pretzel , Isaac A. Adedara , Denis B. Rosemberg
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引用次数: 0
摘要
多巴胺(DA)是一种神经递质,在大脑生理中发挥着重要作用。多巴胺介导的信号变化与多种神经精神疾病的病理生理学有关。双相情感障碍(BD)是一种精神疾病,其特征是躁狂/躁狂和抑郁情绪交替出现。在实验研究中,使用 GBR 12909 对 DA 再摄取进行药理抑制是诱发双相情感障碍样表型的一种工具。斑马鱼(Danio rerio)等替代模式生物被认为是研究包括 BD 在内的不同神经精神疾病所涉及的神经行为变化的重要系统。在此,我们将讨论使用 GBR 12909 作为一种新型药理学策略,在斑马鱼模型中模拟 BD 类表型。我们还强调了斑马鱼体内保存完好的由 DA 介导的信号传导,以及多巴胺能生物标记物在大脑中的早期表达,尤其是多巴胺转运体(DAT),它是 GBR 12909 的主要靶点。最后,我们讨论了该领域的潜在优势和局限性、在BD研究中使用GBR 12909的前景,以及在使用基于斑马鱼的模型的转化方法中如何评估不同的验证标准(即表面效度、预测效度和构建效度)。
The dopamine transporter inhibition using GBR 12909 as a novel pharmacological tool to assess bipolar disorder-like neurobehavioral phenotypes in zebrafish
Dopamine (DA) is a neurotransmitter that plays an important role in brain physiology. Changes in DA-mediated signaling have been implicated with the pathophysiology of various neuropsychiatric conditions. Bipolar disorder (BD) is a mental disorder, characterized by alterning between manic/hypomanic and depressive mood. In experimental research, the pharmacological inhibition of DA reuptake using GBR 12909 serves as a tool to elicit BD-like phenotypes. Alternative model organisms, such as the zebrafish (Danio rerio), have been considered important systems for investigating the neurobehavioral changes involved in different neuropsychiatric conditions, including BD. Here, we discuss the use of GBR 12909 as a novel pharmacological strategy to mimic BD-like phenotypes in zebrafish models. We also emphasize the well-conserved DA-mediated signaling in zebrafish and the early expression of dopaminergic biomarkers in the brain, especially focusing on dopamine transporter (DAT), the main target of GBR 12909. Finally, we discuss potential advantages and limitations in the field, the perspectives of using GBR 12909 in BD research, and how distinct validation criteria (i.e., face, predictive, and construct validity) can be assessed in translational approaches using zebrafish-based models.
期刊介绍:
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.