Copper (Cu^(2+)) induces degeneration of dopaminergic neurons in the nigrostriatal system of rats

作     者：于文然 姜宏 王俊 谢俊霞 Wen-Ran YU;Hong JIANG;Jun WANG;Jun-Xia XIE

作者机构：青岛大学生理学教研室生理学国家重点(培育)学科青岛266071 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2008年第24卷第2期

页      面：73-78页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071006[理学-神经生物学] 

基　　金：National Natural Science Foundation of China,NSFC: 30570649 Major State Basic Research Development Program of China: 2007CB516701 

主　　题：copper substantia nigra dopamine rats 

摘      要：Objective To study the effects of intranigral injection of different doses of CuSO45H2O on dopaminergic neuron in the nigrostriatal system of rats. Methods Wistar rats were divided into four groups, including control group, 10 nmol, 50 nmol and 200 nmol copper injected into left substantia nigra （SN） groups. Seven days after the intranigral injection of copper, dopamine （DA） contents in the striatum （Str） were measured by high performance lipid chromotophotography （HPLC）; the density of tyrosine hydroxylase （TH） positive axons in the Str was measured by TH staining method; TH and Caspase-3 mRNA expression in the SN were measured by semi-quantitative RT-PCR. We detected the activity of superoxide dismutase （SOD） in the lesioned midbrain of rats using biochemical methods. Results DA and its metabolites contents had no significant difference between control group and low dose （10 nmol） copper group. But from 50 nmol copper group, DA contents in the lesioned sides were reduced with the increase in the copper doses injected, showing a significant linear correlation （F = 34.16, P 〈 0.01）. In the 50 nmol copper group, TH positive axons in the Str decreased compared with those of the control and unlesioned sides （F = 121.9, P 〈 0.01）. In the 50 nmol copper group, TH mRNA expression decreased （t =3.12, P 〈 0.01） while Caspase-3 mRNA expression increased （t =8.96, P 〈 0.01） in the SN compared with the control. SOD activity decreased in the midbmin of rots treated with 50 nmol copper compared with that of the control （t = 2.33, P〈0.01）. Conclusion Copper could induce damage of dopaminergic neurons in the SN of rats through destroying antioxidant defenses and promoting apoptosis.