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(P<0.01)。另外,UCN抑制作用可被AST明显拮抗(P<0.01),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(P<0.01)。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。
Aim To investigate the effects of endocrinal petptide urocortin on subthalamic nucleus（ STN）neuron ＇s discharge, also observe the convergence effect of UCN with dopamine（ DA） and glutamate（ GLU）,so as to understand the regulation effects of UCN and its mechanism in Parkinson＇s disease（ PD）.Methods Forty Sprague-Dawley rats were used in this experiment. Nerve electrophysiology method-microiontophoresis was used to observe the effects of UCN on STN neuron firing rates and firing wave. Astressin（ AST,the blocker of CRF receptor 2）,protein kinase A（ PKA） were used to observe the effects of UCN whether via CRF-2R and PKA signal pathway. Moreover,given UCN during the period of DA and GLU,the effects of UCN on DA and GLU in STN neurons were determined. Results During the period of using the UCN,UCN could inhibit the firing rate of 82%（ 27/33） STN neuron（ P 〈0. 01）,and the firing discharge rates were reduced from（ 3. 65 ± 0. 27） Hz to（ 2. 05 ±0. 33） Hz（ P 〈0. 01）. However,the inhibitory effects of UCN in STN could be antagonized by AST. Given UCN during the period of microiontophoresis of inhibitory neurotransmitter（ DA） and excited neurotransmitter（ GLU）,UCN could enhance the effects of DA and attenuate the excitatory effects of GLU（ P 〈0. 01）.Conclusion UCN and GLU/DA in STN,UCN play inhibitory and regulated effects on STN neurotransmitters（ DA and GLU） via CRF-2 receptor and PKA signal pathway.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2017年第10期1425-1430,共6页
Chinese Pharmacological Bulletin
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)
关键词
丘脑底核
多巴胺
谷氨酸
帕金森疾病
优洛可定
微电泳
subthalamic nucleus
dopamine
gluta mate
Parkinson ＇s disease
urocortin
microionto phoresis
