Borlongan C V, Koutouzis T K, Poulos S G, Saporta S, Sanberg P R
Department of Surgery, University of South Florida College of Medicine, Tampa 33612, USA.
Cell Transplant. 1998 Mar-Apr;7(2):131-5. doi: 10.1177/096368979800700208.
We investigated the 3-nitropropionic acid (3-NP)-induced hypoactive model of Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can ameliorate behavioral deficits associated with a more advanced stage of HD. Twelve-week-old Sprague-Dawley rats were introduced to the 3-NP dosing regimen (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested for general spontaneous locomotor activity in the Digiscan locomotor apparatus. All rats displayed significant hypoactivity compared to their pre-3-NP injection locomotor activity. Randomly selected rats then received bilateral intrastriatal solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from embryonic day 14 rat fetuses. Approximately 1/3 of each LGE in hibernation medium was infused into each lesioned host striatum. In control rats, medium alone was infused intrastriatally. A 3-mo posttransplant maturation period was allowed prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited a significant increase in locomotor activity compared to their post-3-NP injection activity or to the controls' posttransplant activity. Surviving striatal grafts were noted in functionally recovered animals. This observation supports the use of fetal striatal transplants to correct the akinetic stage of HD. To the best of our knowledge, this is the first study that has investigated the effects of fetal striatal transplantation in a hypoactive model of HD.
我们研究了3-硝基丙酸（3-NP）诱导的亨廷顿舞蹈病（HD）低活性模型，以证明胎儿组织移植是否能改善与HD更晚期相关的行为缺陷。将12周龄的Sprague-Dawley大鼠采用3-NP给药方案（10mg/kg，腹腔注射，每4天一次，连续28天），然后在Digiscan运动装置中测试其一般自发运动活性。与注射3-NP前的运动活性相比，所有大鼠均表现出明显的运动活性降低。然后随机选择的大鼠接受来自胚胎第14天大鼠胎儿的胎儿纹状体（外侧神经节隆起，LGE）组织的双侧纹状体内实体移植。将处于冬眠培养基中的每个LGE的约1/3注入每个受损宿主纹状体。在对照大鼠中，仅将培养基注入纹状体内。在进行运动活性测试前给予3个月的移植后成熟期。与注射3-NP后的活性或对照组移植后的活性相比，接受胎儿LGE移植的动物的运动活性显著增加。在功能恢复的动物中发现有存活的纹状体移植。这一观察结果支持使用胎儿纹状体移植来纠正HD的运动不能阶段。据我们所知，这是第一项研究胎儿纹状体移植在HD低活性模型中作用的研究。
