Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan.
Sci Rep. 2019 Nov 8;9(1):16344. doi: 10.1038/s41598-019-52735-z.
Idiopathic restless legs syndrome (RLS) has a genetic basis wherein BTBD9 is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of BTBD9 and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of Btbd9 mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS.
特发性不宁腿综合征 (RLS) 具有遗传基础，BTBD9 与 RLS 的风险增加相关。与健康人群相比，血液透析患者也表现出更高的 RLS 发生率。然而，BTBD9 与终末期肾病与 RLS 病理生理学之间的关系知之甚少。在这里，我们评估了给予特发性或由终末期肾病引起的 RLS（肾性 RLS）患者的血清后 Btbd9 突变 (MT) 小鼠的睡眠和腿部肌肉活动，并研究了多巴胺激动剂罗替高汀治疗的效果。在基线时，与野生型 (WT) 小鼠相比，MT 小鼠的快速眼动 (REM) 睡眠量减少，非快速眼动 (NREM) 睡眠期间腿部肌肉活动增加。在 WT 和 MT 小鼠中，注射 RLS 患者的血清会减弱罗替高汀的促醒作用。仅在注射特发性和肾性 RLS 患者血清的 MT 小鼠中，NREM 睡眠期间的腿部肌肉活动增加。随后用罗替高汀治疗可改善这种腿部肌肉活动的改变。这些结果共同支持了先前的报告，表明 Btbd9/多巴胺系统与 RLS 之间存在关系，并部分阐明了 RLS 的病理生理学。
