Yamamoto Hideko, Imai Kazuhide, Takamatsu Yukio, Kamegaya Etsuko, Kishida Makiko, Hagino Yoko, Hara Yasuhiro, Shimada Kiyo, Yamamoto Toshifumi, Sora Ichiro, Koga Hisashi, Ikeda Kazutaka
Department of Molecular Psychiatry, Tokyo Institute Psychiatry, 2-1-8 Kamikitazawa, Tokyo 156-8585, Japan.
Brain Res Mol Brain Res. 2005 Jun 13;137(1-2):40-6. doi: 10.1016/j.molbrainres.2005.02.028. Epub 2005 Mar 31.
Amphetamine abuse may be associated with adaptive changes in gene expression. In the present study, we used a newly developed cDNA array system comprising mouse KIAA (mKIAA) cDNA clones to examine changes in gene expression after chronic methamphetamine (MAP) treatment. Mice were daily treated with saline or MAP (2 mg/kg, ip) for 2 weeks. Approximately 800 mKIAA clones were blotted onto a nylon membrane and hybridized with 33P-labeled DNA derived from mRNAs from mouse whole brain. MAP-induced changes were found in several clones by using whole brain mRNA. Since gene expression of Per2, one of the period protein-related proteins, was the most affected by MAP treatment, its expression was further analyzed in pooled hippocampi from 20 mice that had been treated with saline or MAP (2 mg/kg, ip) for 2 weeks. The gene expression and protein expression of Per2 in the hippocampus were increased by MAP treatment. In the hippocampus, Per2 gene expression was under the regulation of circadian rhythm and increases in Per2 expression were due to the phase shift induced by chronic MAP treatment. These findings suggest that unique expression changes of period protein-related proteins in the hippocampus occur in MAP abuse.
苯丙胺滥用可能与基因表达的适应性变化有关。在本研究中，我们使用了一种新开发的包含小鼠KIAA（mKIAA）cDNA克隆的cDNA阵列系统，来检测慢性甲基苯丙胺（MAP）处理后基因表达的变化。小鼠每天接受生理盐水或MAP（2mg/kg，腹腔注射）处理，持续2周。将大约800个mKIAA克隆点样到尼龙膜上，并与来自小鼠全脑mRNA的33P标记DNA杂交。通过使用全脑mRNA，在几个克隆中发现了MAP诱导的变化。由于周期蛋白相关蛋白之一的Per2的基因表达受MAP处理影响最大，因此在20只分别接受生理盐水或MAP（2mg/kg，腹腔注射）处理2周的小鼠的合并海马体中进一步分析了其表达。MAP处理可增加海马体中Per2的基因表达和蛋白表达。在海马体中，Per基因表达受昼夜节律调节，Per2表达增加是由于慢性MAP处理诱导的相位偏移所致。这些发现表明，MAP滥用会导致海马体中周期蛋白相关蛋白出现独特的表达变化。
