Neuroscience Graduate Program, University of Cincinnati, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Neurosci Biobehav Rev. 2022 Jan;132:621-637. doi: 10.1016/j.neubiorev.2021.11.041. Epub 2021 Nov 27.
Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8-12 % of children and >4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl cyclase-c KO mice, and latrophilin-3 KO mice and rats. Environmental factors thought to contribute to ADHD include ethanol, nicotine, PCBs, lead (Pb), ionizing irradiation, 6-hydroxydopamine, neonatal hypoxia, some pesticides, and organic pollutants. Model validation criteria are outlined, and current genetic models evaluated against these criteria. Future research should explore induced multiple gene KOs given that ADHD is polygenic and epigenetic contributions. Furthermore, genetic models should be combined with environmental agents to test for interactions.
注意缺陷多动障碍（ADHD）是一种多基因神经发育障碍，影响 8-12%的儿童和>4%的成年人。环境因素被认为与遗传易感性相互作用，增加了患 ADHD 的易感性。目前没有一种啮齿动物模型能捕捉到 ADHD 的所有方面，但有几种模型有希望。主要的遗传模型包括自发性高血压大鼠、多巴胺转运蛋白敲除（KO）小鼠、多巴胺受体亚型 KO 小鼠、Snap-25 KO 小鼠、鸟苷酸环化酶-c KO 小鼠和 latrophilin-3 KO 小鼠和大鼠。被认为与 ADHD 有关的环境因素包括乙醇、尼古丁、多氯联苯、铅（Pb）、电离辐射、6-羟多巴胺、新生儿缺氧、一些杀虫剂和有机污染物。概述了模型验证标准，并根据这些标准评估了当前的遗传模型。未来的研究应该探索诱导的多个基因 KO，因为 ADHD 是多基因的，并且存在表观遗传的贡献。此外，应该将遗传模型与环境因素结合起来，以测试相互作用。
