Park Jung-Eun, Lee Soon-Tae, Im Woo-Seok, Chu Kon, Kim Manho
Neurodegeneration Research Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Neurosci Lett. 2008 Dec 19;448(1):143-7. doi: 10.1016/j.neulet.2008.10.020. Epub 2008 Oct 14.
The acetylcholinesterase inhibitor (AChEI) galantamine is currently used to treat mild to moderate Alzheimer's disease (AD), and it has been suggested to have several neuroprotective effects. To investigate the potential application of this drug to the treatment of Huntington's disease, we examined whether galantamine can reduce the striatal degeneration induced by the mitochondrial toxin, 3-nitropropionic acid (3NP). 3NP (63 mg/kg/day) was delivered to Lewis rats by osmotic pumps for 5 consecutive days, and the rats received intraperitoneal administration of either different concentrations of galantamine (1mg/kg/day or 10 mg/kg/day, twice daily) or vehicle (saline) throughout the experiment. Galantamine attenuated the 3NP-induced neurologic deficits on days 2-5. Galantamine-treated rats showed smaller striatal lesion volumes measured by Nissl staining and lower numbers of TUNEL(+) apoptotic cells when compared to the vehicle-treated rats. Galantamine failed to reduce the striatal lesion volume when co-administered with mecamylamine, a nicotinic acetylcholine receptor antagonist. Our data indicate that galantamine can attenuate neurodegeneration in a Huntington's disease model by modulating nAChR.
乙酰胆碱酯酶抑制剂（AChEI）加兰他敏目前用于治疗轻度至中度阿尔茨海默病（AD），并且有人提出它具有多种神经保护作用。为了研究这种药物在治疗亨廷顿舞蹈病中的潜在应用，我们检测了加兰他敏是否能减轻线粒体毒素3-硝基丙酸（3NP）诱导的纹状体变性。通过渗透泵连续5天将3NP（63毫克/千克/天）给予Lewis大鼠，并且在整个实验过程中，大鼠腹腔注射不同浓度的加兰他敏（1毫克/千克/天或10毫克/千克/天，每日两次）或赋形剂（生理盐水）。加兰他敏在第2至5天减轻了3NP诱导的神经功能缺损。与用赋形剂处理的大鼠相比，用加兰他敏处理的大鼠经尼氏染色测量的纹状体损伤体积更小，并且TUNEL（+）凋亡细胞数量更少。当与烟碱型乙酰胆碱受体拮抗剂美加明共同给药时，加兰他敏未能减少纹状体损伤体积。我们的数据表明，加兰他敏可通过调节烟碱型乙酰胆碱受体来减轻亨廷顿舞蹈病模型中的神经变性。
