Consensus guidelines on the construct validity of rodent models of restless legs syndrome.
Consensus guidelines on the construct validity of rodent models of restless legs syndrome.
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DOI：
10.1242/dmm.049615
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发表时间：
2022-08-01
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
我们对不宁腿综合征（RLS）的病因和自然病程的了解是不完整的。缺乏客观的诊断性生物标志物仍然是临床研究和有效动物模型开发的挑战。作为一个临床前和临床科学家的工作组，我们之前已经定义了RLS啮齿动物模型的面部效度参数。在本文中，我们建立了新的RLS啮齿动物模型构建效度的准则。为此，我们首先确定并同意影响RLS表达的风险、触发因素和病理生理机制。然后，我们选择了20个被认为在文献中有足够支持的项目，我们根据性别和遗传因素、铁相关机制、电生理机制、多巴胺能机制、暴露于中枢神经系统活性药物等进行分组。然后将这些因素和生物学机制转化为啮齿类动物的生物等效物，认为最适合啮齿动物的RLS模型。我们还确定了评估和量化这些生物等效物的参数。研究这些因素，无论是单独的还是联合的，将有助于确定它们在啮齿动物RLS样表型表达中的具体作用，这将为RLS的诊断和治疗提供重要的翻译意义。摘要：我们总结了国际不宁腿综合征研究小组最近建立的关于不宁腿综合征啮齿动物模型构建效度的共识指南。
Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS. Summary: We summarize the consensus guidelines on the construct validity of rodent models of restless legs syndrome, which have been recently established by a task force of the International Restless Legs Syndrome Study Group.
影响因子：
4.6
作者：
Watanabe T;Sasaki M;Komagata S;Tsukano H;Hishida R;Kohno T;Baba H;Shibuki K
通讯作者：
Shibuki K