Collier T J, Elsworth J D, Taylor J R, Sladek J R, Roth R H, Redmond D E
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, NY 14642.
Neuroscience. 1994 Aug;61(4):875-89. doi: 10.1016/0306-4522(94)90410-3.
Previous studies of rats in our laboratory indicate that a molecule or molecules released by Schwann cells exert survival and growth-promoting effects on mesencephalic dopamine neurons. In the present study, we have begun to investigate the potential for Schwann cell augmentation of host dopamine fiber systems and embryonic dopamine neuron grafts in non-human primates. Ten adult male St Kitts African Green monkeys treated with the dopaminergic neurotoxin 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine one year previously, but behaviorally asymptomatic, served as hosts for implant studies. A segment of young adult monkey saphenous nerve was collected to serve as an implanted tissue source of Schwann cell-derived growth factors. Nerve was enclosed in a hollow semi-permeable polymer fiber for implantation into the lateral ventricle, with embryonic ventral mesencephalic tissue co-grafts containing developing dopamine neurons aimed at nearby locations in the caudate nucleus. Control implants consisted of an empty polymer fiber co-grafted with embryonic ventral mesencephalon. Our morphological observations indicate that while no clear augmentation of the morphology of grafted dopamine neurons attributable to co-grafted nerve was observed, this lack of influence may be related to the spatial separation of the co-grafted tissues. In contrast, some monkeys with nerve segments in the lateral ventricle exhibited increased tyrosine hydroxylase-positive fiber staining in the immediately adjacent lateral septal area and the ventricular wall of the caudate nucleus. This enhancement was not associated with empty polymer implants. Levels of dopamine and its metabolite homovanillic acid derived from tissue punches in the caudate nucleus and septal area support the view that monkeys exhibiting morphological enhancement of host dopamine systems also show biochemical increases in dopamine levels and changes in the direction of normalization of the homovanillic acid/dopamine ratio. Biochemical values from a single septal area tissue punch in one animal were an exception to this rule. This study suggests that while the utility of peripheral nerve as a source of dopamine graft augmentation in non-human primates remains to be demonstrated, grafted nerve has a stimulatory effect on host brain dopamine systems in adult, dopamine-depleted monkeys, and that this morphological effect can be dissociated from previously hypothesized injury-induced regeneration.
我们实验室之前对大鼠的研究表明，雪旺氏细胞释放的一种或多种分子对中脑多巴胺神经元具有存活和促生长作用。在本研究中，我们已开始研究在非人类灵长类动物中，雪旺氏细胞增强宿主多巴胺纤维系统和胚胎多巴胺神经元移植的潜力。十只成年雄性圣基茨非洲绿猴，一年前接受了多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶治疗，但行为上无症状，作为植入研究的宿主。收集一段成年幼猴的隐神经，作为雪旺氏细胞衍生生长因子的植入组织来源。将神经包裹在中空的半透性聚合物纤维中，植入侧脑室，同时将含有发育中多巴胺神经元的胚胎腹侧中脑组织共同移植到尾状核附近位置。对照植入物由与胚胎腹侧中脑共同移植的空聚合物纤维组成。我们的形态学观察表明，虽然未观察到因共同移植神经而使移植的多巴胺神经元形态明显增强，但这种缺乏影响可能与共同移植组织的空间分离有关。相比之下，一些侧脑室中有神经节段的猴子，在紧邻的外侧隔区和尾状核室壁中，酪氨酸羟化酶阳性纤维染色增加。这种增强与空聚合物植入物无关。来自尾状核和隔区组织打孔的多巴胺及其代谢物高香草酸水平支持这样一种观点：即表现出宿主多巴胺系统形态增强的猴子，其多巴胺水平在生化上也会增加，并且高香草酸/多巴胺比值会朝着正常化方向变化。一只动物单个隔区组织打孔的生化值是此规则的一个例外。这项研究表明，虽然外周神经作为非人类灵长类动物多巴胺移植增强来源的效用仍有待证明，但移植的神经对成年多巴胺缺乏的猴子的宿主脑多巴胺系统具有刺激作用，并且这种形态学效应可以与先前假设中的损伤诱导再生区分开来。
