Gabazine对小鼠苍白球神经元放电的影响
摘要
苍白球存在于基底神经节间接环路,对机体正常运动行为以及运动障碍疾病均发挥显著作用。帕金森病(Parkinson's disease, PD)是由基底神经节功能障碍所导致的运动性疾病。苍白球主要接受从纹状体以及苍白球神经元自身侧支发出的Y-氨基丁酸(GABA)能纤维支配。GABA是基底神经节核团中主要的具有抑制性效应的神经递质。苍白球内GABA发挥其抑制性效应主要通过作用于突触后膜的GABAA受体。以往大量实验证实GABA或者GABAA受体与帕金森病有着密切的联系。早期行为学实验结果显示经苍白球内注射GABAA受体阻断剂bicuculline可以起到抗帕金森病效应。因此,探讨苍白球内源性GABAA递质系统对于认识苍白球在正常及病理状态下的功能活动显得十分重要。目的：探讨正常及帕金森病状态下苍白球内源性GABAA受体的效应。方法：本实验用甲基苯基四氢毗啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)制备帕金森病模型小鼠,采用细胞外电生理学记录的方法观察GABAA受体阻断剂gabazine对正常及帕金森病模型小鼠苍白球神经元放电的影响。结果：
1.在正常小鼠苍白球内注射0.1 mM gabazine使苍白球神经元放电频率由7.2±1.4 Hz升高到10.4±1.8 Hz(P<0.001),平均增加53.7±8.0%(n=15),与生理盐水组相比明显增强,差别有统计学意义(P<0.001)。
2.在MPTP制备的帕金森病模型小鼠,苍白球压力注射0.1 mM gabazine可以兴奋苍白球神经元,使其放电频率由5.3±2.2 Hz升高至6.8±2.7 Hz(P<0.01),平均增加42.9±7.5%,与生理盐水对照组相比,明显增加苍白球神经元放电频率,差别有显著统计学意义(P<0.001),与正常小鼠相比(53.7±8.0%,n=15)没有统计学差别。
结论：Gabazine可兴奋正常及MPTP制备的帕金森病模型小鼠苍白球神经元,这将为进一步认识苍白球内源性GABAA受体治疗帕金森病提供了一定的实验依据。
The globus pallidus occupies an important position in the indirect pathway of the basal ganglia, and it plays an important role in normal movement regulation and in basal ganglia movement disorders. The globus pallidus mainly receives gamma-aminobutyric acid (GABA)ergic inputs from the striatum and local axon collaterals. GABA is the major inhibitory neurotransmitter used in the basal ganglia. A line of evidence indicated that there is a close relationship between GABA or GABAA receptors and Parkinson's disease. Early study revealed that microinjection of GABAA receptor antagonist, bicuculline, into the globus pallidus had marked antiparkinsonian effects. Therefore, it is very important to investigate the endogenous GABA transmitter system for understanding the function of globus pallidus under normal and pathologic state. Object:To investigate the electrophysiological effects of endogenous GABAA receptor in the globus pallidus of normal and MPTP parkinsonian mice. Methods:The parkisonian mice was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vivo extracellular recording was used to detect the effects of GABAA receptor antagonist, gabazine, on spontaneous firing rate of pallidal neurons in normal and pakinsonian mice. Results:
1. In normal mice, micro-pressure ejection of gabazine increased the spontaneous firing rate of pallidal neurons from 7.2±1.4 Hz to 10.4±1.8 Hz (P<0.001). The average increase was 53.7±8.0%, which was significantly different (P<0.001) from that of vehicle (normal saline) injection.
2. In MPTP treated mice, micro-pressure ejection of gabazine increased the spontaneous firing rate of pallidal neurons from 5.3±2.2 Hz to 6.8±2.7 Hz (P<0.01). The average increase was 42.9±7.5%, which was significantly different (P<0.001) from that of normal saline injection (P<0.001). Gabazine-induced increase in firing rate of globus pallidus had no significant difference in normal and MPTP treated parkinsonian mice.
Conclusion:Gabazine increased the firing rate of globus pallidus neurons in normal and MPTP treated parkinsonian mice. The present findings may provide theoretical foundation for further investigations into the potential of pallidal endogenous GABAA receptor in treating Parkinson's disease.
1.在正常小鼠苍白球内注射0.1 mM gabazine使苍白球神经元放电频率由7.2±1.4 Hz升高到10.4±1.8 Hz(P<0.001),平均增加53.7±8.0%(n=15),与生理盐水组相比明显增强,差别有统计学意义(P<0.001)。
2.在MPTP制备的帕金森病模型小鼠,苍白球压力注射0.1 mM gabazine可以兴奋苍白球神经元,使其放电频率由5.3±2.2 Hz升高至6.8±2.7 Hz(P<0.01),平均增加42.9±7.5%,与生理盐水对照组相比,明显增加苍白球神经元放电频率,差别有显著统计学意义(P<0.001),与正常小鼠相比(53.7±8.0%,n=15)没有统计学差别。
结论：Gabazine可兴奋正常及MPTP制备的帕金森病模型小鼠苍白球神经元,这将为进一步认识苍白球内源性GABAA受体治疗帕金森病提供了一定的实验依据。
The globus pallidus occupies an important position in the indirect pathway of the basal ganglia, and it plays an important role in normal movement regulation and in basal ganglia movement disorders. The globus pallidus mainly receives gamma-aminobutyric acid (GABA)ergic inputs from the striatum and local axon collaterals. GABA is the major inhibitory neurotransmitter used in the basal ganglia. A line of evidence indicated that there is a close relationship between GABA or GABAA receptors and Parkinson's disease. Early study revealed that microinjection of GABAA receptor antagonist, bicuculline, into the globus pallidus had marked antiparkinsonian effects. Therefore, it is very important to investigate the endogenous GABA transmitter system for understanding the function of globus pallidus under normal and pathologic state. Object:To investigate the electrophysiological effects of endogenous GABAA receptor in the globus pallidus of normal and MPTP parkinsonian mice. Methods:The parkisonian mice was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vivo extracellular recording was used to detect the effects of GABAA receptor antagonist, gabazine, on spontaneous firing rate of pallidal neurons in normal and pakinsonian mice. Results:
1. In normal mice, micro-pressure ejection of gabazine increased the spontaneous firing rate of pallidal neurons from 7.2±1.4 Hz to 10.4±1.8 Hz (P<0.001). The average increase was 53.7±8.0%, which was significantly different (P<0.001) from that of vehicle (normal saline) injection.
2. In MPTP treated mice, micro-pressure ejection of gabazine increased the spontaneous firing rate of pallidal neurons from 5.3±2.2 Hz to 6.8±2.7 Hz (P<0.01). The average increase was 42.9±7.5%, which was significantly different (P<0.001) from that of normal saline injection (P<0.001). Gabazine-induced increase in firing rate of globus pallidus had no significant difference in normal and MPTP treated parkinsonian mice.
Conclusion:Gabazine increased the firing rate of globus pallidus neurons in normal and MPTP treated parkinsonian mice. The present findings may provide theoretical foundation for further investigations into the potential of pallidal endogenous GABAA receptor in treating Parkinson's disease.
引文
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