Xue Yan, Yang Yu-Ting, Liu Hong-Yun, Chen Wen-Fang, Chen An-Qi, Sheng Qing, Chen Xin-Yi, Wang Ying, Chen Hua, Liu Hong-Xia, Pang Ya-Yan, Chen Lei
Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
Department of Pathology, Qingdao Municipal Hospital, Qingdao, China.
Eur J Neurosci. 2016 Sep;44(5):2247-57. doi: 10.1111/ejn.13323. Epub 2016 Jul 13.
Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease.
食欲素是一种神经肽，最初在下丘脑中被发现。苍白球是基底神经节的关键结构，参与正常运动功能和运动障碍。形态学研究表明，OX1和OX2受体在苍白球中均有表达。采用单单位细胞外记录和行为测试，研究了食欲素A在苍白球中的直接体内电生理和行为效应。微量注射食欲素A显著提高了苍白球神经元的自发放电率。相关性分析显示食欲素A诱导的兴奋与基础放电率之间呈负相关。此外，应用特异性OX1受体拮抗剂SB-334867可降低苍白球神经元的放电率，提示内源性食欲素能系统调节苍白球神经元的放电活动。食欲素A通过OX1和OX2受体增加苍白球神经元的兴奋性。在6-羟基多巴胺帕金森病大鼠中，食欲素A诱导苍白球神经元放电率增加比正常大鼠更强。免疫染色显示正常和帕金森病大鼠苍白球中均有OX1受体阳性表达。最后，姿势测试表明，在全身给予氟哌啶醇的情况下，单侧微量注射食欲素A会导致对侧偏斜。进一步的身体摆动测试显示，苍白球食欲素A和SB-334867分别诱导对侧偏向摆动和同侧偏向摆动。基于食欲素A在苍白球中的电生理和行为学发现，本研究结果可能为帕金森病的发病机制和治疗提供理论依据。
