Maeda T, Ibi M, Shimazu S, Akaike A
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Jpn J Pharmacol. 1998 Jun;77(2):161-7. doi: 10.1254/jjp.77.161.
We examined the role of striatal cells in cytotoxicity induced by N-methyl-D-aspartate (NMDA) in dopamine (DA) neurons in rat mesencephalic slice culture. Coronal sections were prepared from 2- and 3-day-old rat brains and cultured using the interface culture method for 2-3 weeks before the NMDA cytotoxicity experiment. The exposure of mesencephalic cultures without striatum (single culture) to NMDA (10-300 microM) for 24 hr reduced the number of DA neurons in a concentration-dependent manner. The co-administration of the non-competitive NMDA-receptor antagonist significantly inhibited the neurotoxic effect of NMDA. When mesencephalon and striatum were kept in contact and co-cultured (contacting co-cultures), the growth of DA fibers into the striatal part was observed. In the contacting co-cultures with striatum, the minimal effective concentration for NMDA cytotoxicity was higher than that in single cultures. The contacting co-cultures with cerebellum did not alter the NMDA cytotoxicity. When the mesencephalon and striatum slices were kept apart and co-cultured, the co-cultures showed neither an outgrowth of DA fibers to the striatum nor any effect on the NMDA cytotoxicity. These results suggest that the projection of rat mesencephalic DA neurons to the striatum attenuates the NMDA cytotoxicity in DA neurons themselves.
我们研究了纹状体细胞在大鼠中脑切片培养中，对N-甲基-D-天冬氨酸（NMDA）诱导的多巴胺（DA）神经元细胞毒性作用中所起的作用。从2日龄和3日龄大鼠的大脑制备冠状切片，并采用界面培养法培养2至3周，然后进行NMDA细胞毒性实验。将没有纹状体的中脑培养物（单一培养物）暴露于NMDA（10 - 300微摩尔）24小时，会以浓度依赖的方式减少DA神经元的数量。非竞争性NMDA受体拮抗剂的共同给药显著抑制了NMDA的神经毒性作用。当中脑和纹状体保持接触并共同培养（接触性共培养）时，观察到DA纤维向纹状体部分生长。在与纹状体的接触性共培养中，NMDA细胞毒性的最小有效浓度高于单一培养物中的浓度。与小脑的接触性共培养并未改变NMDA细胞毒性。当中脑和纹状体切片分开并共同培养时，共培养物既未显示DA纤维向纹状体的生长，也未对NMDA细胞毒性产生任何影响。这些结果表明，大鼠中脑DA神经元向纹状体的投射减弱了DA神经元自身的NMDA细胞毒性。
