黑质区微注射鱼藤酮对大鼠纹状体和丘脑腹外侧核神经元电活动的影响
发布时间：2018-11-12 10:40
【摘要】： 作为曾被广泛使用的农药，鱼藤酮(Rotenone)能诱发类帕金森症(Parkinson's Disease，PD)的神经毒性作用近年来引起关注。然而以往的研究大多采用外周暴露方法，观察脑内特异性神经病理学变化和行为学改变，而对由病理学变化引发PD运动障碍所涉及的基底神经节及运动丘脑神经元电活动机制却较少报道。 本工作以SD大鼠为研究对象，检测鱼藤酮脑内微注射是否诱导类似PD运动行为障碍及黑质DA能神经元特异性病理学变化，并进一步探讨其对纹状体和丘脑腹外侧核神经元电活动的影响，分析诱发运动障碍的可能神经机制。 主要结果如下： 1．2μg，3μg和5μg剂量鱼藤酮暴露21天后，大鼠在垂直网格上的移动延时与对照组和自身暴露前比较均有显著性延长，并且随着鱼藤酮暴露剂量增大而延长；大鼠从斜板上滑落的次数显著性增多。在开阔试验中，鱼藤酮暴露组大鼠探洞的次数和直立的时间与暴露前比较均显著性减少，且呈现一定的剂量效应关系。在半数动物上观察到鱼藤酮暴露所诱发的震颤症状。 2．免疫组化实验结果显示，鱼藤酮暴露后黑质致密部酪氨酸羟化酶表达阳性的神经元数目显著下降，并随着暴露剂量增大神经元损失相应增多。残存TH阳性神经元细胞萎缩，神经突起减少或消失，显示进行性退化特征。 3．鱼藤酮暴露后大鼠纹状体神经元的自发放电型式有所改变，呈混合簇状放电神经元显著增加，单脉冲和不规律型放电神经元显著减少；自发放电频数明显增加。与对照组相比，鱼藤酮暴露后纹状体神经元对刺激运动皮层的诱发电活动呈现兴奋性增强的趋势，反应延时则减少。 4．鱼藤酮暴露后呈爆发式自发放电的丘脑腹外侧核(VL核)神经元显著增多，自发放电的频数普遍降低，放电频谱峰向低频区聚集。鱼藤酮暴露使得对运动皮层刺激表现为兴奋的VL神经元相对减少，而对刺激的反应延时较对照组显著增加。 上述结果表明，黑质区直接微注射鱼藤酮可诱导大鼠出现运动迟缓，肌肉僵直，震颤等典型类帕金森症的征状；并导致黑质致密部多巴胺能神经元进行性损失这一典型帕金森症病理学改变。鱼藤酮暴露导致纹状体神经元自发活动增强及对运动皮层刺激兴奋性效应增加，反映纹状体神经元活动增强可能与PD特异性运动障碍相关联。鱼藤酮暴露后丘脑腹外侧核神经元爆发型自发放电增多，提示丘脑腹外侧核神经元电活动可能与PD运动滞缓、震颤等行为学变化关系密切。本文的工作为中枢直接暴露鱼藤酮建立PD动物模型提供了参考，为在纹状体和丘脑腹外侧核实施手术治疗PD提供了理论依据，同时就纹状体和丘脑腹外侧核参与运动调控的机制提供了佐证。
[Abstract]:As a widely used pesticide, rotenone (Rotenone) can induce neurotoxicity of Parkinson's disease (Parkinson's Disease,PD). However, previous studies have mostly used peripheral exposure methods to observe specific neuropathological and behavioral changes in the brain. However, the mechanism of electrical activity of basal ganglion and motor thalamic neurons involved in PD motor dysfunction caused by pathological changes is seldom reported. In this study, SD rats were studied to detect whether rotenone microinjection induced PD motility disorder and specific pathological changes of substantia nigra DA neurons. Furthermore, the effect on the electrical activity of striatum and ventrolateral thalamus neurons was investigated, and the possible neural mechanism of motor disorder was analyzed. The main results were as follows: after exposure to 1.2 渭 g rotenone 3 渭 g and 5 渭 g rotenone for 21 days, the movement delay on vertical grid was significantly prolonged in rats compared with control group and self exposure. And it was prolonged with the increase of rotenone exposure dose. The number of falls from the inclined plate increased significantly in rats. In the open test, the number of holes and the time to stand upright in rotenone exposure group were significantly decreased compared with those before exposure, and there was a dose-effect relationship between rotenone and rotenone exposure group. Tremors induced by rotenone exposure were observed in half of the animals. 2. The results of immunohistochemistry showed that the number of tyrosine hydroxylase positive neurons in substantia nigra was significantly decreased after rotenone exposure, and the loss of neurons increased with the increase of exposure dose. The residual TH positive neurons atrophy, the neurites decreased or disappeared, showing progressive degeneration. 3. The spontaneous discharge pattern of striatum neurons was changed after rotenone exposure, the mixed cluster firing neurons increased significantly, the monopulse and irregular firing neurons decreased significantly, and the frequency of spontaneous discharge increased significantly. Compared with the control group, the striatal neurons showed an excitatory tendency to stimulate the motor cortex after rotenone exposure, and the response delay was decreased. 4. After exposure to rotenone, the neurons in the ventrolateral thalamic nucleus (VL) with explosive spontaneous discharges increased significantly, the frequency of spontaneous discharges decreased generally, and the peak of the discharge spectrum gathered to the low frequency region. Rotenone exposure resulted in a relative decrease in the number of VL neurons excited by motor cortex stimuli, while the delay in response to the stimuli was significantly increased compared with the control group. These results suggest that the direct microinjection of rotenone in the substantia nigra can induce the symptoms of typical Parkinson's disease such as motor retardation muscle stiffness and tremor in rats. It also leads to progressive loss of dopaminergic neurons in the substantia nigra compact, a typical pathological change in Parkinson's disease. Rotenone exposure resulted in increased spontaneous activity of striatum neurons and an increase in excitability of motor cortex stimulation, suggesting that increased activity of striatum neurons might be associated with PD specific motor dysfunction. After rotenone exposure, the burst spontaneous discharges of neurons in the ventrolateral thalamic nucleus increased, suggesting that the electrical activity of neurons in the ventrolateral thalamic nucleus might be closely related to the behavioral changes such as PD motility retardation and tremor. Our work provides a reference for the establishment of PD animal model by central direct exposure to rotenone, and provides a theoretical basis for the surgical treatment of PD in striatum and ventrolateral thalamus. It also provides evidence for the mechanism of striatum and ventrolateral nucleus of thalamus involved in motor regulation.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363
本文编号：2326872
[Abstract]:As a widely used pesticide, rotenone (Rotenone) can induce neurotoxicity of Parkinson's disease (Parkinson's Disease,PD). However, previous studies have mostly used peripheral exposure methods to observe specific neuropathological and behavioral changes in the brain. However, the mechanism of electrical activity of basal ganglion and motor thalamic neurons involved in PD motor dysfunction caused by pathological changes is seldom reported. In this study, SD rats were studied to detect whether rotenone microinjection induced PD motility disorder and specific pathological changes of substantia nigra DA neurons. Furthermore, the effect on the electrical activity of striatum and ventrolateral thalamus neurons was investigated, and the possible neural mechanism of motor disorder was analyzed. The main results were as follows: after exposure to 1.2 渭 g rotenone 3 渭 g and 5 渭 g rotenone for 21 days, the movement delay on vertical grid was significantly prolonged in rats compared with control group and self exposure. And it was prolonged with the increase of rotenone exposure dose. The number of falls from the inclined plate increased significantly in rats. In the open test, the number of holes and the time to stand upright in rotenone exposure group were significantly decreased compared with those before exposure, and there was a dose-effect relationship between rotenone and rotenone exposure group. Tremors induced by rotenone exposure were observed in half of the animals. 2. The results of immunohistochemistry showed that the number of tyrosine hydroxylase positive neurons in substantia nigra was significantly decreased after rotenone exposure, and the loss of neurons increased with the increase of exposure dose. The residual TH positive neurons atrophy, the neurites decreased or disappeared, showing progressive degeneration. 3. The spontaneous discharge pattern of striatum neurons was changed after rotenone exposure, the mixed cluster firing neurons increased significantly, the monopulse and irregular firing neurons decreased significantly, and the frequency of spontaneous discharge increased significantly. Compared with the control group, the striatal neurons showed an excitatory tendency to stimulate the motor cortex after rotenone exposure, and the response delay was decreased. 4. After exposure to rotenone, the neurons in the ventrolateral thalamic nucleus (VL) with explosive spontaneous discharges increased significantly, the frequency of spontaneous discharges decreased generally, and the peak of the discharge spectrum gathered to the low frequency region. Rotenone exposure resulted in a relative decrease in the number of VL neurons excited by motor cortex stimuli, while the delay in response to the stimuli was significantly increased compared with the control group. These results suggest that the direct microinjection of rotenone in the substantia nigra can induce the symptoms of typical Parkinson's disease such as motor retardation muscle stiffness and tremor in rats. It also leads to progressive loss of dopaminergic neurons in the substantia nigra compact, a typical pathological change in Parkinson's disease. Rotenone exposure resulted in increased spontaneous activity of striatum neurons and an increase in excitability of motor cortex stimulation, suggesting that increased activity of striatum neurons might be associated with PD specific motor dysfunction. After rotenone exposure, the burst spontaneous discharges of neurons in the ventrolateral thalamic nucleus increased, suggesting that the electrical activity of neurons in the ventrolateral thalamic nucleus might be closely related to the behavioral changes such as PD motility retardation and tremor. Our work provides a reference for the establishment of PD animal model by central direct exposure to rotenone, and provides a theoretical basis for the surgical treatment of PD in striatum and ventrolateral thalamus. It also provides evidence for the mechanism of striatum and ventrolateral nucleus of thalamus involved in motor regulation.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363
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