Embryonic substantia nigra grafts in the mesencephalon send neurites to the host striatum in non-human primate after overexpression of GDNF.
Embryonic substantia nigra grafts in the mesencephalon send neurites to the host striatum in non-human primate after overexpression of GDNF.
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DOI：
10.1002/cne.22028
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Sladek JR Jr
中科院分区：
文献类型：
--
作者：
Redmond DE Jr;Elsworth JD;Roth RH;Leranth C;Collier TJ;Blanchard B;Bjugstad KB;Samulski RJ;Aebischer P;Sladek JR Jr
尽管使用异位移植多巴胺生成细胞治疗帕金森病取得了部分成功，但如果可能的话，恢复原始神经解剖回路可能会效果更好。先前放置在黑质（SN）中的腹侧中脑（VM）移植物的正常解剖学投影的证据仅限于新生啮齿动物和双移植或桥接手术。本研究试图确定将有效的生长促进因子——胶质细胞源性神经营养因子（GDNF）注射到目标区域或将胎儿纹状体共移植物放置在黑质纹状体通路中是否可能引起尾状核的神经炎生长。四只成年圣基茨绿猴接受了胚胎 VM 移植到宿主黑质附近的头侧中脑，并将 AAV2/GDNF 或 EIAV/GDNF 注射到尾状核中。三只成年猴在黑质附近与胎儿 VM 组织共同移植，并在黑质纹状体通路中 2.5 mm 喙侧移植胎儿纹状体移植物 (STR)。处死前，向纹状体目标区域注射逆行示踪剂荧光金（FG）。仅在接受 AAV2/GDNF 载体注射到同侧纹状体的猴子的 SN 中的 VM 移植物中的酪氨酸羟化酶标记的神经元中发现了 FG 标记。当在同一侧注射 FG 标记时，所有猴子在宿主黑质中都显示出 FG 标记。这些数据表明，移植的多巴胺能神经元可以将神经突延伸到远处目标，释放浓度升高的 GDNF，并表明可以将移植的神经元置于适当的位点以进行潜在的束重建。
In spite of partial success in treating Parkinson's disease using ectopically placed grafts of dopamine-producing cells, restoration of the original neuroanatomical circuits, if possible, might work better. Previous evidence of normal anatomic projections from ventral mesencephalic (VM) grafts placed in the substantia nigra (SN) has been limited to neonatal rodents and double grafting or bridging procedures. This study attempted to determine whether injection of a potent growth promoting factor, glial cell line-derived neurotrophic factor (GDNF), into the target regions or placement of fetal striatal co-grafts in the nigrostriatal pathway might elicit neuritic outgrowth to the caudate nucleus. Four adult St. Kitts green monkeys received embryonic VM grafts into the rostral mesencephalon near the host substantia nigra, and injections of AAV2/GDNF or EIAV/GDNF into the caudate. Three adult monkeys were co-grafted with fetal VM tissue near the substantia nigra and fetal striatal grafts (STR) 2.5 mm rostral in the nigrostriatal pathway. Before sacrifice, the striatal target regions were injected with the retrograde tracer fluorogold (FG). FG label was found in tyrosine hydroxylase-labeled neurons in VM grafts in the SN of only those monkeys that received AAV2/GDNF vector injections into the ipsilateral striatum. All monkeys showed FG labeling in the host substantia nigra when FG labeling was injected on the same side. These data show that grafted dopaminergic neurons can extend neurites to a distant target releasing an elevated concentration of GDNF, and suggest that grafted neurons can be placed into appropriate loci for potential tract reconstruction.
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影响因子：
82.9
作者：
Mendez, Ivar;Vinuela, Angel;Isacson, Ole
通讯作者：
Isacson, Ole
影响因子：
3.3
作者：
Brecknell, JE;Haque, NSK;Dunnett, SB
通讯作者：
Dunnett, SB
影响因子：
56.9
作者：
LIN, LFH;DOHERTY, DH;COLLINS, F
通讯作者：
COLLINS, F
影响因子：
11.2
作者：
Ma, YL;Feigin, A;Eidelberg, D
通讯作者：
Eidelberg, D
影响因子：
2.9
作者：
Mendez, I;Hong, M
通讯作者：
Hong, M