淀粉样β蛋白对爪蟾卵母细胞表达的老龄大鼠脑神经递质受体功能影响的初步研究  

Preliminary studies on the effects of β amyloid protein 1-40 on the expressed neurotransmitter receptors in Xenopus oocytes microinjected with mRNA from aged rat brain tissues

作　　者：黄福南[1] 李文彬[1] 张炳烈[1] 崔旭[1] 韩志涛[1] 房征宇[1] 蔡竖平[1] 

机构地区：[1]北京解放军总医院老年医学研究所老年神经科,100853

出　　处：《中华神经科杂志》2000年第4期20-22,共3页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目(39470761);军队九五科研基金资助项目(98Q091)

摘　　要：目的　观察淀粉样β蛋白 (Aβ)对老龄鼠脑神经递质受体功能的影响 ,探讨Aβ和神经递质受体介导的阿尔茨海默病发病机制。方法　采用电压钳位技术记录表达到非洲爪蟾卵母细胞膜上的神经递质受体通道电流 ,了解其电流特性并观察 2 0nmol L和 6 0nmol L淀粉样 β蛋白1 40(Aβ1 40 )作用 12、2 4、96h对表达的老龄鼠脑乙酰胆碱 (ACh)及谷氨酸受体电流的影响。结果　爪蟾卵母细胞能表达老龄大鼠脑的ACh、谷氨酸、多巴胺和γ 氨基丁酸受体 ,其受体通道复合物电流均由Cl 1离子载导。表达的老龄大鼠脑ACh、谷氨酸、多巴胺受体峰电流比成年组明显减低。Aβ1 40 对表达到爪蟾卵母细胞膜上的ACh受体功能有抑制作用 ,而对谷氨酸受体的电流有增强效应。 2 0nmol LAβ1 40 作用 12hACh峰电流由 (90 .90± 14.14)nA下降为 (80 .6 7± 16 .2 4)nA(P <0 .0 5 ) ,最强时下降 2 3%。 2 0nmol LAβ1 40 作用于谷氨酸受体 96h峰电流即有增强 ,6 0nmol L作用 12h其电流由 (85 .2 5± 10 .82 )nA上升为 (10 2 .13± 2 1.6 3)nA (P <0 .0 1)。结论　淀粉样 β蛋白对老龄大鼠脑神经递质受体的作用因受体种类的不同而有差异 ,这种差异提示不同的受体在AD病因病理学机制中的不同作用。Objective It was designed to observe the effects of β amyloid protein on the functions of neurotransmitter receptors and to disclose the possible pathophysiological mechanism of Alzheimer disease(AD) mediated by β amyloid protein and neurotransmitter receptors. Methods Messenger RNA was taken from brains of aged Wistar rats with Promega kits and microinjected into Xenopus oocytes for receptor expression. The currents of expressed receptors and the effects of Aβ 1 40 on them were detected with the double electrode voltage clamps technique. Results ACh, glutamate, dopamine and GABA receptors were successively expressed in Xenopus oocytes. The currents of these expressed receptors detected with voltage clamps were carried by chloride ions with their equibrillium potentials close to 22 mV. Currents of expressed ACh, glutamate, dopamine receptors in the aged rats decreased more significantly than those in adult young rats. Aβ had a reverse effect on the functions of ACh and glutamic acid receptors. Aβ 1 40 enhanced significantly the currents of expressed glutamate receptors when it inhibited markedly the currents of expressed ACh receptors. The currents induced by 10 -4 mol/L ACh decreased from (90.90±14.14) nA to (80.67±16.24) nA ( P <0.05) in the oocytes treated with 20 nmol/L Aβ 1 40 over 12 h. The decreased percentage of currents reached 23%. The current potentiation appeared after the oocytes being treated with 20 nmol/L Aβ 1 40 over 96 h, whereas after the oocytes being treated with 60 nmol/L Aβ 1 40 over 12 h the currents potentiated and induced by 10 -3 mol/L glutamate went up from (85.25±10.82) nA to (102.13± 21.63) nA ( P <0.01). There were no differences in the levels of total RNA and mRNA between the aged and young adult rat brains. Conclusions There are differences between the effects of Aβ on different types of neurotransmitter receptors. These differences may explain the mechanisms of different neurotransmitter receptors in

关 键 词：淀粉样Β蛋白 受体 神经递质 衰老 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学]