Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Neurochem Int. 2010 Oct;57(3):288-96. doi: 10.1016/j.neuint.2010.06.007. Epub 2010 Jun 17.
Cerebellar mechanisms were explored underlying the effects of amphetamine (Amph) on the brain, by monitoring primarily the neurochemistry of the cerebellum. Adult mice received repeated intermittent injections of d-Amph, 5mg/kg or saline, twice daily for three days and once on day 4. As revealed by the biochemical analysis, the levels of GABA content were increased by 68-93% in the cerebellar vermis and hemisphere of mice at 4h after the first (acute) or the last (repeated) Amph injections, though the glutamate content was unaltered, compared to the respective saline-treated controls. By contrast, at 4h post-repeated Amph, in the vermis, the level of norepinephrine was approximate 38% lower than the corresponding control and 5-hydroxytryptamine (5-HT) resembled the control, whereas in the hemisphere, the norepinephrine content was similar to control and 5-HT 66% higher, implying cerebellar lobe-dependent changes. However, in both lobes, at 4h after the acute and repeated Amph exposures, changes of the transmitter content were correlated with reductions of 50-64% in the levels of the phosphorylated (p) MAP kinase (K) expression and 39-55% in the calbindin-D28k (CB) of the Purkinje cell somata, and increases of 289-556% in pCREB, 373-594% c-FOS, and 51-76% calretinin of the granular layer, as shown by immunohistochemical analysis. The up-regulated GABA content in the vermis and hemisphere may be associated with the decreased expression of Purkinje somatal CB and pMAPK, implicating a relation between the Ca(2+) of Purkinje cells and the level of GABA. Furthermore, the prominent increases of the granular layer pCREB, c-FOS and calretinin may influence the activity of Purkinje cells, which are known to be modulated by the granule cells. The data indicate that the Amph exposure selectively alters specific transmitters in the cerebellar lobes and modifies the cellular expression of distinct signaling proteins in the cerebellar layers.
小脑机制是通过监测小脑的神经化学物质来探索安非他命（Amph）对大脑影响的。成年小鼠接受重复间歇性注射 d-安非他命，5mg/kg 或生理盐水，每天两次，共三天，第四天一次。生化分析显示，与相应的生理盐水处理对照组相比，第一次（急性）或最后一次（重复） Amph 注射后 4 小时，小鼠小脑蚓部和半球的 GABA 含量分别增加 68-93%，而谷氨酸含量不变。相比之下，在重复 Amph 后 4 小时，蚓部的去甲肾上腺素水平比相应的对照低约 38%，5-羟色胺（5-HT）与对照相似，而在半球，去甲肾上腺素含量与对照相似，5-HT 增加 66%，提示小脑叶依赖性变化。然而，在两个叶，在急性和重复 Amph 暴露后 4 小时，递质含量的变化与磷酸化（p）MAP 激酶（K）表达水平降低 50-64%和浦肯野细胞胞体钙结合蛋白-D28k（CB）降低 39-55%相关，而 pCREB 增加 289-556%，c-FOS 增加 373-594%，颗粒层 calretinin 增加 51-76%，如免疫组织化学分析所示。蚓部和半球中 GABA 含量的增加可能与浦肯野细胞胞体 CB 和 pMAPK 表达降低有关，提示浦肯野细胞的 Ca(2+)与 GABA 水平之间存在关系。此外，颗粒层中 pCREB、c-FOS 和 calretinin 的显著增加可能会影响浦肯野细胞的活性，而众所周知，颗粒细胞会调节浦肯野细胞。数据表明，Amph 暴露选择性地改变了小脑叶中的特定递质，并改变了小脑层中不同信号蛋白的细胞表达。
