Kim Sunyoun, Nam Jungmin, Kim Kisok
Department of Safety Evaluation, Biotoxtech Company, Chungbuk 363-883, Korea.
Hum Exp Toxicol. 2007 Sep;26(9):741-6. doi: 10.1177/0960327107083973.
Aluminum (Al) has been identified as a potential contributing factor in the etiology of several neurodegenerative disorders, but data regarding specific effects on neurotransduction, especially on dopaminergic neurotransduction, are lacking. The objective of this study was to determine the extent of expressional alterations in dopamine receptors (DRs) in two dopaminergic subtypes, D1 and D2, in low and high dose Al-treated mice. After administration of Al (four intraperitoneal injections of 30 or 60 mg/kg AlCl3.6H2O at 2 h intervals), expression of the dopamine D1-like and D2-like receptors (DRD1, DRD2) was examined in the cortex and striatum of mouse brain at bregma levels of 1.10, -0.10 and -1.34 mm. In the cortex, Al treatment decreased densities of DRD1 and DRD2 in a dose-dependent manner at all three bregma levels, especially in the high-dose Al group. Similarly, DRD1 and DRD2 expression in the striatum also exhibited dose dependency and statistically significant decreases were seen in the high-dose group, except in the striatum at bregma level - 1.34. These findings suggest that DR in the caudal striatum is more resistant to the effects of Al exposure than DR in the cortex or rostral striatum. In addition, our results suggest that disturbance of dopaminergic neurotransmission mediated by DRD1 and/or DRD2 may be involved in the pathogenesis of Al neurotoxicity.
铝（Al）已被确定为几种神经退行性疾病病因中的一个潜在因素，但关于其对神经传导，尤其是对多巴胺能神经传导的具体影响的数据尚缺。本研究的目的是确定在低剂量和高剂量铝处理的小鼠中，两种多巴胺能亚型D1和D2的多巴胺受体（DRs）表达改变的程度。给予铝（以2小时间隔腹腔注射4次30或60mg/kg的AlCl3·6H2O）后，在脑坐标为1.10、-0.10和-1.34mm处的小鼠脑皮质和纹状体中检测多巴胺D1样和D2样受体（DRD1、DRD2）的表达。在皮质中，铝处理在所有三个脑坐标水平均以剂量依赖方式降低DRD1和DRD2的密度，尤其是在高剂量铝组中。同样，纹状体中的DRD1和DRD2表达也表现出剂量依赖性，并且在高剂量组中观察到统计学上显著的降低，但在脑坐标水平-1.34处的纹状体除外。这些发现表明，尾侧纹状体中的DR比皮质或吻侧纹状体中的DR对铝暴露的影响更具抗性。此外，我们的结果表明，由DRD1和/或DRD2介导的多巴胺能神经传递紊乱可能参与铝神经毒性的发病机制。
