Conditional neural knockout of the adenosine A(2A) receptor and pharmacological A(2A) antagonism reduce pilocarpine-induced tremulous jaw movements: studies with a mouse model of parkinsonian tremor.
Conditional neural knockout of the adenosine A(2A) receptor and pharmacological A(2A) antagonism reduce pilocarpine-induced tremulous jaw movements: studies with a mouse model of parkinsonian tremor.
复制标题
条件性神经敲除腺苷 A(2A) 受体和药理学 A(2A) 拮抗作用可减少毛果芸香碱引起的下颌震颤运动：帕金森震颤小鼠模型的研究。
DOI：
10.1016/j.euroneuro.2012.08.004
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Correa,Mercè
中科院分区：
文献类型：
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作者：
Salamone,JohnD;Collins-Praino,LyndseyE;Pardo,Marta;Podurgiel,SamanthaJ;Baqi,Younis;Müller,ChristaE;Schwarzschild,MichaelA;Correa,Mercè
颤抖的下巴运动是下巴的快速垂直偏转，类似于咀嚼，但不针对任何特定的刺激。在大鼠中，许多与人类帕金森综合症相似的情况都可以诱导颤抖的下巴运动，包括多巴胺耗竭、多巴胺拮抗和胆碱类似物药物。此外，抗帕金森病药物如L多巴、多巴胺激动剂、毒扁豆碱拮抗剂和腺苷A2A拮抗剂可减弱大鼠的震颤下巴运动。在本研究中，我们建立了一种小鼠震颤下颌运动模型，以研究腺苷A2受体拮抗剂和条件性神经元敲除腺苷A2受体对类胆碱诱导的震颤下颌运动的影响。M受体激动剂匹罗卡品以剂量依赖方式(0.25~1.0 mg/kg ip)显著诱导大鼠震颤下巴运动。这些运动主要发生在3-7.5赫兹的本地频率范围内。注射腺苷A2受体拮抗剂MSX-3(2.5-10.0 mg/kg ip)可显著减弱匹罗卡品引起的下巴颤动。此外，与小鼠相比，腺苷A2受体基因敲除小鼠在匹罗卡品诱导的颤抖下巴运动中表现出显著的减少。这些结果证明了在小鼠上颌骨颤动模型的可行性，并提示腺苷A2受体拮抗和缺失能够减少拟胆碱诱发的小鼠上颌骨颤动。未来的研究应该使用小鼠抖动下巴的模型来调查额外的遗传操作的影响。
Tremulous jaw movements are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rats, tremulous jaw movements can be induced by a number of conditions that parallel those seen in human parkinsonism, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Moreover, tremulous jaw movements in rats can be attenuated using antiparkinsonian agents such as L-DOPA, dopamine agonists, muscarinic antagonists, and adenosine A2Aantagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A2Aantagonism, and a conditional neuronal knockout of adenosine A2Areceptors, on cholinomimetic-induced tremulous jaw movements. The muscarinic agonist pilocarpine significantly induced tremulous jaw movements in a dose-dependent manner (0.25–1.0 mg/kg IP). These movements occurred largely in the 3–7.5 Hz local frequency range. Administration of the adenosine A2Aantagonist MSX-3 (2.5–10.0 mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A2Areceptor knockout mice showed a significant reduction in pilocarpine-induced tremulous jaw movements compared to littermate controls. These results demonstrate the feasibility of using the tremulous jaw movement model in mice, and indicate that adenosine A2Areceptor antagonism and deletion are capable of reducing cholinomimetic-induced tremulous jaw movements in mice. Future studies should investigate the effects of additional genetic manipulations using the mouse tremulous jaw movement model.