Striatal histamine mechanism in the pathogenesis of restless legs syndrome.
Striatal histamine mechanism in the pathogenesis of restless legs syndrome.
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DOI：
10.1093/sleep/zsz223
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发表时间：
2020-02-13
期刊：
影响因子：
5.6
通讯作者：
Siegel JM
中科院分区：
文献类型：
--
作者：
Lai YY;Hsieh KC;Cheng YH;Chew KT;Nguyen D;Ramanathan L;Siegel JM
不宁腿综合征（RLS）被假设是由纹状体多巴胺传输异常引起的。多巴胺能药物可有效治疗 RLS。然而，长期使用多巴胺能药物会引起不良反应。我们使用缺铁 (ID) 和铁替代 (IR) 大鼠来研究 RLS 的神经病理学，并确定组胺 H3 受体 (H3R) 拮抗剂是否可能是一种有用的治疗方法。组胺 H3R 拮抗剂已被证明可降低运动活动。对照和 ID 大鼠通过手术植入电极用于多导睡眠图记录。基线多导睡眠图记录 3 天后，大鼠全身注射 H3R 激动剂 α-甲基组胺和拮抗剂硫哌丁胺。注射药物后继续记录。通过蛋白质印迹法测定对照、ID 和 IR 大鼠的纹状体 H3R 水平。收集对照大鼠、ID大鼠和IR大鼠的血液用于测量血细胞比容水平。 α-甲基组胺和硫过酰胺分别增加和减少对照大鼠的运动活动。在 ID 大鼠中，α-甲基组胺对运动活动没有影响，而硫哌丁胺则减少睡眠中的周期性腿部运动 (PLM)。睡眠-觉醒状态在任何条件下都没有显着改变。 ID大鼠的纹状体H3R水平最高，IR大鼠的纹状体H3R水平为中等至低水平，对照大鼠的纹状体H3R水平最低。还发现纹状体 H3R 水平分别与睡眠中的 PLM 和血细胞比容水平呈正相关和负相关。纹状体组胺机制可能与 ID 性贫血引起的不宁腿综合征有关。组胺 H3R 拮抗剂可用于治疗 RLS。
Restless legs syndrome (RLS) has been hypothesized to be generated by abnormal striatal dopamine transmission. Dopaminergic drugs are effective for the treatment of RLS. However, long-term use of dopaminergic drugs causes adverse effects. We used iron-deficient (ID) and iron-replacement (IR) rats to address the neuropathology of RLS and to determine if a histamine H3 receptor (H3R) antagonist might be a useful treatment. Histamine H3R antagonists have been shown to decrease motor activity. Control and ID rats were surgically implanted with electrodes for polysomnographic recording. After 3 days of baseline polysomnographic recordings, rats were systemically injected with the H3R agonist, α-methylhistamine, and antagonist, thioperamide. Recordings were continued after drug injection. Striatal H3R levels from control, ID, and IR rats were determined by western blots. Blood from control, ID, and IR rats was collected for the measurement of hematocrit levels. α-Methylhistamine and thioperamide increased and decreased motor activity, respectively, in control rats. In ID rats, α-methylhistamine had no effect on motor activity, whereas thioperamide decreased periodic leg movement (PLM) in sleep. Sleep–wake states were not significantly altered under any conditions. Striatal H3R levels were highest in ID rats, moderate to low in IR rats, and lowest in control rats. Striatal H3R levels were also found to positively and negatively correlate with PLM in sleep and hematocrit levels, respectively. A striatal histamine mechanism may be involved in ID anemia-induced RLS. Histamine H3R antagonists may be useful for the treatment of RLS.
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