Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced Locomotor Abnormalities in Rats.
Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced Locomotor Abnormalities in Rats.
复制标题
食欲素/下丘脑分泌素系统在大鼠前庭病变引起的运动异常中作用的证据
DOI：
10.3389/fnins.2016.00355
复制
发表时间：
2016
影响因子：
4.3
通讯作者：
Cai Y
中科院分区：
文献类型：
--
作者：
Pan L;Qi R;Wang J;Zhou W;Liu J;Cai Y
前庭损伤可引起动物和人类的运动异常。双侧前庭功能缺失的啮齿动物表现为前庭功能缺失综合征，如绕圈、斜拉肌以及运动和探索亢进。先前的研究已经调查了前庭功能丧失后多巴胺系统的变化，但结果不一致且不确定。大量证据表明，食欲素系统与中枢运动控制有关。我们假设食欲素可能潜在地参与了前庭功能丧失引起的运动障碍。在本研究中，我们采用免疫组织化学方法检测了氨基苯甲酸酯或3,3′-亚氨基二丙腈（IDPN）诱导的大鼠前庭病变（AVL或IVL）对下丘脑食欲素- a （OXA）标记的影响。使用组胺H4受体拮抗剂JNJ7777120 （20 mg/kg, ig）记录并验证前庭病变引起的运动异常。我们还研究了食欲素受体1型拮抗剂SB334867 （16 μg, icc.v）对这些行为反应的影响。在avl和IVL后72小时，动物在家养笼子中表现出前庭功能障碍综合征和运动亢进。JNJ7777120显著缓解了这些反应，同时也消除了avl诱导的开放性探索行为的增加。AVL动物下丘脑中oxa标记的神经元数量在AVL后72 h和IVL动物在IVL后24、48和72 h显著增加。SB334867在avl和IVL后72小时显著减轻前庭功能障碍综合征和运动多动。它还减少了AVL动物的探索行为。这些结果提示，OXA表达的改变可能与急性前庭损伤后运动异常有关。食欲素受体可能是前庭功能障碍的潜在治疗靶点。
Vestibular damage can induce locomotor abnormalities in both animals and humans. Rodents with bilateral vestibular loss showed vestibular deficits syndrome such as circling, opisthotonus as well as locomotor and exploratory hyperactivity. Previous studies have investigated the changes in the dopamine system after vestibular loss, but the results are inconsistent and inconclusive. Numerous evidences indicate that the orexin system is implicated in central motor control. We hypothesized that orexin may be potentially involved in vestibular loss-induced motor disorders. In this study, we examined the effects of arsanilate- or 3,3′-iminodipropionitrile (IDPN)-induced vestibular lesion (AVL or IVL) on the orexin-A (OXA) labeling in rat hypothalamus using immunohistochemistry. The vestibular lesion-induced locomotor abnormalities were recorded and verified using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.). The effects of the orexin receptor type 1 antagonist SB334867 (16 μg, i.c.v.) on these behavior responses were also investigated. At 72 h post-AVL and IVL, animals exhibited vestibular deficit syndrome and locomotor hyperactivity in the home cages. These responses were significantly alleviated by JNJ7777120 which also eliminated AVL-induced increases in exploratory behavior in an open field. The numbers of OXA-labeled neurons in the hypothalamus were significantly increased in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48, and 72 h post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory behavior in the AVL animals. These results suggested that the alteration of OXA expression might contribute to locomotor abnormalities after acute vestibular lesion. The orexin receptors might be the potential therapeutic targets for vestibular disorders.