Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys
Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys
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DOI：
10.1016/0306-4522(95)00564-1
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发表时间：
1996-05-01
期刊：
影响因子：
3.3
通讯作者：
Roth, RH
中科院分区：
文献类型：
--
作者：
Elsworth, JD;Sladek, JR;Roth, RH
在接受胚胎多巴胺神经元纹状体内移植的帕金森氏症灵长类动物中观察到的行为改善机制尚未完全确定。移植神经元产生多巴胺可能是行为恢复的基础。或者，移植过程本身对宿主多巴胺系统的刺激可能是结果的核心。本研究检查了移植后1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）处理的灵长类动物尾状核中多巴胺浓度是否升高，如果是，升高是否依赖于（i）植入套管的引入（假手术），（ii）移植的脑区，或（iii）移植的胎儿组织的胎龄。早期胎龄胎儿腹侧中脑移植（胚胎40-50天）与尾状核多巴胺浓度的显著升高有关，平均约为20%，与尾状核中更远的部位相比，移植物附近（2 mm内）的对照值。与早期胎龄胎儿腹侧中脑，移植部位附近的高香草酸/多巴胺浓度的比值正常化相比，在远离移植部位的尾状核中发现的升高值。晚期胎儿腹侧中脑、胎儿小脑或假植入的移植物并未增加移植部位附近的多巴胺浓度或降低高香草酸/多巴胺比率。生化和组织化学证据表明，宿主多巴胺神经元终止于延髓核不是变化的来源。大量的酪氨酸羟化酶阳性神经元在移植部位只观察到在MPTP治疗的猴子，接受移植的早期胎龄胎儿腹侧mesencephalon.These数据提供了强有力的支持，这一假设的多巴胺来源于移植的多巴胺神经元是主要的基础，我们的MPTP治疗的猴子纹状体内移植后观察到的行为恢复。
The mechanism of the behavioral improvement observed in parkinsonian primates that receive intrastriatal transplants of fetal dopamine neurons has not been firmly established. Dopamine production by grafted neurons may be the basis of the behavioral recovery. Alternatively, stimulation of the host dopamine system by the transplant procedure itself may be central to the outcome. The present study examined whether dopamine concentration was raised in the caudate nucleus of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primate following grafting, and if so, whether the elevation was dependent on either (i) the introduction of the implantation cannula (sham), (ii) the brain region that was grafted, or (iii) the gestational age of fetal tissue that was grafted.Transplantation of early gestational age fetal ventral mesencephalon (embryonic days 40-50) was associated with significant elevation of caudate nucleus dopamine concentration to a mean of approximately 20% of control values in the vicinity (within 2 mm) of the graft, compared with more distant sites in the caudate nucleus. With early gestational age fetal ventral mesencephalon, the ratio of homovanillic acid/dopamine concentration near the graft site was normalized compared to the elevated value found in the caudate nucleus distant from the graft site. Grafts of later stage fetal ventral mesencephalon, or fetal cerebellum or sham implantation did not increase dopamine concentration or lower homovanillic acid/dopamine ratio near the graft site. Biochemical and histochemical evidence suggests that host dopamine neurons terminating in the nucleus accumbens are not the source of the changes. Numerous tyrosine hydroxylase-positive neurons at the graft site were only observed in the MPTP-treated monkeys that received grafts of early gestational age fetal ventral mesencephalon.These data lend strong support to the hypothesis that dopamine derived from grafted dopamine neurons is the major basis for behavioral recovery observed following intrastriatal transplantation in our MPTP-treated monkeys.