Earl C D, Reum T, Xie J X, Sautter J, Kupsch A, Oertel W H, Morgenstern R
Institute of Physiology, University of Munich, Germany.
Exp Brain Res. 1996 Apr;109(1):179-84. doi: 10.1007/BF00228642.
The present study employed differential-pulse voltammetry to assess the influence of foetal ventral mesencephalic grafts on dopamine overflow in the contralateral caudate putamen of the 6-hydroxydopamine rat model of Parkinson's disease. The experimental design involved measurements of dopamine overflow in the grafted and contralateral striatum. Control measurements of dopamine overflow were performed in 6-hydroxydopamine-lesioned rats only and the caudate putamen of normal control rats. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted into the dopamine-depleted caudate putamen of unilaterally 6-hydroxydopamine-lesioned rats. At 6 weeks, animals with functional, mature grafts (as assessed by amphetamine-amplified behavioural asymmetry), were pretreated with pargyline (75 mg/kg i.p.), and both striatal sides were monitored for dopamine overflow for 90 min following amphetamine sulphate administration (5 mg/kg i.p.). The time course of dopamine overflow inside the graft was similar to that in the contralateral caudate putamen of the same animal, the normal control animal and the contralateral caudate putamen of 6-hydroxydopamine-lesioned animals. However, in grafted animals the mean dopamine overflow detected in the contralateral caudate putamen was approximately 34% lower than the concentration of dopamine detected in the contralateral caudate putamen of 6-hydroxydopamine-lesioned control animals and approximately 39% lower than the concentration of dopamine detected in the caudate putamen of the normal control animal. There was no statistical difference in the concentration of amphetamine-induced dopamine overflow between the caudate putamen contralateral to the 6-hydroxydopamine lesion and the caudate putamen of the normal control animal. These data suggest that intrastriatal foetal ventral mesencephalic suspension grafts reduce amphetamine-induced dopamine release in the contralateral non-grafted caudate putamen.
本研究采用差分脉冲伏安法评估胎儿腹侧中脑移植对帕金森病6-羟基多巴胺大鼠模型对侧尾状核壳核中多巴胺溢出的影响。实验设计包括测量移植侧和对侧纹状体中的多巴胺溢出。仅在6-羟基多巴胺损伤的大鼠以及正常对照大鼠的尾状核壳核中进行多巴胺溢出的对照测量。将胎鼠腹侧中脑组织的细胞悬液移植到单侧6-羟基多巴胺损伤大鼠的多巴胺耗尽的尾状核壳核中。在6周时,对具有功能性、成熟移植体的动物(通过苯丙胺放大的行为不对称性评估)腹腔注射优降宁(75mg/kg)进行预处理,然后在注射硫酸苯丙胺(5mg/kg腹腔注射)后90分钟监测两侧纹状体的多巴胺溢出情况。移植体内多巴胺溢出的时间进程与同一动物的对侧尾状核壳核、正常对照动物以及6-羟基多巴胺损伤动物的对侧尾状核壳核相似。然而,在移植动物中,对侧尾状核壳核中检测到的平均多巴胺溢出量比6-羟基多巴胺损伤对照动物对侧尾状核壳核中检测到的多巴胺浓度低约34%,比正常对照动物尾状核壳核中检测到的多巴胺浓度低约39%。6-羟基多巴胺损伤对侧的尾状核壳核与正常对照动物的尾状核壳核之间,苯丙胺诱导的多巴胺溢出浓度没有统计学差异。这些数据表明,纹状体内胎儿腹侧中脑组织悬液移植可减少对侧未移植尾状核壳核中苯丙胺诱导的多巴胺释放。