School of Pharmacy, University of Camerino, Italy.
Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):1107-19. doi: 10.1177/039463201202500428.
The triorganotin compound trimethyltin (TMT) is a highly toxic molecule which has a great impact on human health. The aim of this study was to investigate the specific alteration of dopamine receptors and transporters in the hippocampus of TMT-treated rats. The TMT-treated group showed impaired spatial reference memory in a Morris water maze task compared to the control group, whereas memory consolidation tested 24 hours after the last training session was preserved. In the open field, TMT-treated rats showed a decrease in time spent in rearing episodes reflecting a lower interest to explore a novel environment. In the hippocampal area of the TMT-treated group, we observed a reduction in neuronal viability accompanied by a significant decrease in the expression of the dopamine receptors (D1 and D2), and dopamine transporters (DAT, VMAT1 and VMAT2). A less pronounced reduction was observed for D3 and D5 while D4 did not change. These data were confirmed by RT-PCR analysis. The present study on TMT-induced neurodegeneration highlights the link between hippocampal asset of dopamine receptors and transporters and the impaired performance of rats in a spatial reference memory task.
三甲基锡(TMT)是一种剧毒分子,对人类健康有重大影响。本研究旨在探讨 TMT 处理大鼠海马多巴胺受体和转运体的特定改变。与对照组相比,TMT 处理组在 Morris 水迷宫任务中表现出空间参考记忆受损,而最后一次训练后 24 小时进行的记忆巩固测试得到保留。在旷场中,TMT 处理组大鼠在直立时间上减少,反映出对探索新环境的兴趣降低。在 TMT 处理组的海马区,我们观察到神经元活力降低,多巴胺受体(D1 和 D2)和多巴胺转运体(DAT、VMAT1 和 VMAT2)的表达显著下降。D3 和 D5 的减少程度较轻,而 D4 没有变化。这些数据通过 RT-PCR 分析得到证实。本研究强调了 TMT 诱导的神经退行性变与海马多巴胺受体和转运体的相关性,以及大鼠在空间参考记忆任务中的表现受损之间的联系。