Orexin excites rat inferior vestibular nuclear neurons via co-activation of OX1 and OX2 receptors

Orexin excites rat inferior vestibular nuclear neurons via co-activation of OX1 and OX2 receptors
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Orexin 通过 OX1 和 OX2 受体的共同激活来兴奋大鼠下前庭核神经元

DOI:
10.1007/s00702-014-1330-z
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发表时间:
2015-06
影响因子:
3.3
通讯作者:
Jian-Jun Wang
Jian-Jun Wang
中科院分区:
医学3区
文献类型:
--
作者:
Lei Yu;Xiao-Yang Zhang;Zhang-Peng Chen;Qian-Xing Zhuang;Jing-Ning Zhu;Jian-Jun Wang

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食欲素缺乏会导致猝倒,这是一种以肌张力突然丧失为特征的运动缺陷,强烈表明中枢食欲素能系统在运动控制中的积极作用。然而,食欲素对中枢运动结构神经元的影响仍然很大程度上未知。我们之前的研究表明,食欲素会兴奋小脑核和前庭外侧核中的神经元,这是控制肌张力的两个重要的皮质下运动中心。在这里,我们报道了orexin-A和orexin-B都可以去极化并增加前庭下核(IVN)神经元的放电率,IVN是前庭核复合体中最大的核,在控制身体姿势的信息信号整合中发挥着重要作用。 TTX 不会阻止食欲素诱导的 IVN 神经元兴奋,表明神经肽具有直接的突触后作用。此外,食欲素的沐浴应用会以浓度依赖性方式在 IVN 神经元上诱导内向电流。 SB334867 和 TCS-OX2-29 是特异性 OX1 和 OX2 受体拮抗剂,可阻断食欲素的兴奋作用,而 [Ala(11), D-Leu(15)]-orexin B 是一种选择性 OX2 受体激动剂,可模拟食欲素诱导的 IVN 神经元内向电流。 qPCR 和免疫荧光结果显示 OX1 和 OX2 受体 mRNA 和蛋白均在大鼠 IVN 中表达和定位。这些结果表明,食欲素通过 OX1 和 OX2 受体的共同激活来兴奋 IVN 神经元,这表明通过直接调节 IVN,中枢食欲素能系统可能积极参与中枢前庭介导的姿势和运动控制。
Orexin deficiency results in cataplexy, a motor deficit characterized by sudden loss of muscle tone, strongly indicating an active role of central orexinergic system in motor control. However, effects of orexin on neurons in central motor structures are still largely unknown. Our previous studies have revealed that orexin excites neurons in the cerebellar nuclei and lateral vestibular nucleus, two important subcortical motor centers for control of muscle tone. Here, we report that both orexin-A and orexin-B depolarizes and increases the firing rate of neurons in the inferior vestibular nucleus (IVN), the largest nucleus in the vestibular nuclear complex and holding an important position in integration of information signals in the control of body posture. TTX does not block orexin-induced excitation on IVN neurons, suggesting a direct postsynaptic action of the neuropeptide. Furthermore, bath application of orexin induces an inward current on IVN neurons in a concentration-dependent manner. SB334867 and TCS-OX2-29, specific OX1 and OX2 receptor antagonists, blocked the excitatory effect of orexin, and [Ala(11), D-Leu(15)]-orexin B, a selective OX2 receptor agonist, mimics the orexin-induced inward current on IVN neurons. qPCR and immunofluorescence results show that both OX1 and OX2 receptor mRNAs and proteins are expressed and localized in the rat IVN. These results demonstrate that orexin excites the IVN neurons by co-activation of both OX1 and OX2 receptors, suggesting that via the direct modulation on the IVN, the central orexinergic system may actively participate in the central vestibular-mediated postural and motor control.
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发表时间: 2014
影响因子: 4.5
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DOI: 10.1016/s0092-8674(00)81965-0
发表时间: 1999-08-06
期刊: CELL
影响因子: 64.5
作者:
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DOI: 10.3233/ves-2009-0348
发表时间: 2009
期刊: Journal of vestibular research : equilibrium & orientation
影响因子: --
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