神经肽优洛可定对丘脑底核神经元自发放电影响与CRF-2R关系研究

发布时间：2019-02-08 17:32

【摘要】：目的研究神经内分泌生物活性肽优洛可定(urocortin,UCN)对丘脑底核(subthalamic nucleus,STN)神经元放电及STN中多巴胺(dopamine,DA)能、谷氨酸(glutamic acid,GLU)能神经传递的影响,研究UCN在STN中是否与GLU及DA存在汇聚作用,探讨UCN在帕金森疾病(Parkinson’s disease,PD)发生中可能发挥的作用。方法取40只SD大鼠,采用神经电生理实验方法中的微电泳技术,在微电泳UCN过程中,观察STN神经元放电的波形及频率变化,同时,微电泳Astressin(AST)及蛋白激酶A(protein kinase A,PKA)抑制剂,观察促皮质素释放因子2型受体(corticotropin releasing factor 2 receptor,CRF-2R)是否参与UCN对STN神经元放电的影响。另外,在微电泳DA和GLU过程中,给予UCN及AST,观察STN神经元放电的变化,明确是否存在DA能及GLU能与UCN的交汇作用。结果微电泳UCN过程中,82%(27/33)STN神经元频率减慢。STN平均放电频率由(3.65±0.27)Hz减少到(2.05±0.33)Hz,微电泳UCN前、后STN放电频率明显降低(P0.01)。另外,UCN抑制作用可被AST明显拮抗(P0.01),UCN抑制作用也可被PKA阻断剂部分阻断。在微电泳抑制性神经递质DA和兴奋性GLU过程中,UCN能进一步协同DA的抑制效应,并明显拮抗GLU的兴奋作用(P0.01)。结论 UCN与DA能及GLU能在STN神经元中存在汇聚作用,UCN可能是通过与CRF-2R结合,进而通过PKA信号通路,影响DA能、GLU能神经递质活动,抑制STN神经元放电。
[Abstract]:Objective to study the effects of neuroendocrine bioactive peptide urocopine (urocortin,UCN) on the discharges of neurons in the subthalamic nucleus (subthalamic nucleus,STN) and the neurotransmission of dopamine (dopamine,DA) and glutamate (glutamic acid,GLU) in STN. To investigate whether UCN converges with GLU and DA in STN and to explore the possible role of UCN in the pathogenesis of Parkinson's disease (Parkinson's disease,PD). Methods 40 SD rats were selected and microelectrophoretic technique was used to observe the waveform and frequency of STN neuron discharge during microelectrophoretic UCN. At the same time, microelectrophoretic Astressin (AST) and protein kinase A (protein kinase A, were used in the process of microelectrophoretic UCN. PKA) inhibitor, to observe whether (corticotropin releasing factor 2 receptor,CRF-2R, a type 2 receptor of corticotropin releasing factor, is involved in the effect of UCN on the firing of STN neurons. In addition, during DA and GLU microelectrophoresis, UCN and AST, were given to observe the changes of the firing of STN neurons to determine whether there existed the interaction of DA energy and GLU with UCN. Results during microelectrophoretic UCN, the frequency of STN neurons decreased in 82% (27 / 33), the average discharge frequency of STN decreased from (3.65 卤0.27) Hz to (2.05 卤0.33) Hz, microelectrophoresis UCN, and the discharge frequency of STN decreased significantly after microelectrophoresis (P0.01). In addition, the inhibitory effect of UCN was significantly antagonized by AST (P0.01), UCN also partially blocked by PKA blocker. In the process of inhibitory neurotransmitter DA and excitatory GLU, UCN could further enhance the inhibitory effect of DA and antagonize the excitatory effect of GLU (P0.01). Conclusion UCN, DA and GLU can converge in STN neurons. UCN may affect the activity of DA and GLU neurotransmitters and inhibit the firing of STN neurons through the combination of CRF-2R and PKA signaling pathway.
【作者单位】：汕头大学医学院第二附属医院神经外科;锦州医科大学药理学教研室;
【基金】：广东省医学科学技术研究基金(No A2015085) 国家大学生创新基金(No 201610160042)
【分类号】：R742.5

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