Department of Biology, Temple University Philadelphia, PA 19122, USA.
Neurosci Lett. 2012 May 16;516(2):167-70. doi: 10.1016/j.neulet.2012.03.034. Epub 2012 Mar 21.
Transgenic Drosophila melanogaster carrying the human gene for alpha synuclein is an animal model for the study of Parkinson's Disease. Climbing activity in these flies is reduced as a result of the effect of this protein on the locomotor activity of the transgenic fly. L-DOPA and gamma amino butyric acid (GABA) reverse the loss of this activity when placed in the food fed to these flies. While muscimol, a GABA(A) receptor agonist has no effect in this system, baclofen and the allosteric agonists CG 7930 and GS 39783 which affect the GABA(B) receptor reverse this activity. This latter effect is eliminated when these compounds are fed in conjunction with the GABA(B) receptor antagonist 2-hydroxysaclofen. In addition, fendiline which is a Ca(++) receptor blocker also reverses the loss of climbing ability. Because there is a calcium channel close to the GABA(B) receptor on the cell surface, these data are indicative of a relationship between the roles of the GABA(B) receptor, the calcium channel and the effect of alpha-synuclein on the motor activity of the transgenic fly.
携带人类α-突触核蛋白基因的转基因黑腹果蝇是研究帕金森病的动物模型。由于这种蛋白质对转基因果蝇的运动活性的影响，这些果蝇的攀爬活性降低。当将 L-DOPA 和γ-氨基丁酸 (GABA) 放置在这些果蝇所食用的食物中时，可逆转这种活性的丧失。虽然 GABA(A) 受体激动剂 muscimol 在该系统中没有作用，但影响 GABA(B) 受体的 baclofen 和别构激动剂 CG 7930 和 GS 39783 可逆转这种活性。当这些化合物与 GABA(B) 受体拮抗剂 2-羟基 saclofen 一起喂食时，这种后一种作用会被消除。此外，钙通道阻滞剂芬迪利也可逆转攀爬能力的丧失。因为在细胞表面上靠近 GABA(B) 受体存在钙通道，所以这些数据表明 GABA(B) 受体、钙通道和α-突触核蛋白对转基因果蝇运动活性的作用之间存在关系。
