Chermenina M, Schouten P, Nevalainen N, Johansson F, Orädd G, Strömberg I
Integrative Medical Biology, Umeå University, 901 87 Umeå, Sweden.
Integrative Medical Biology, Umeå University, 901 87 Umeå, Sweden.
Neuroscience. 2014 Jun 13;270:1-11. doi: 10.1016/j.neuroscience.2014.04.008. Epub 2014 Apr 12.
Glial cell line-derived neurotrophic factor (GDNF) exerts neuroprotective and neurorestorative effects on neurons and GDNF plays a significant role in maintenance of the dopamine neurons utilizing grafting to create a nigrostriatal microcircuit of Gdnf knockout (Gdnf(-/-)) tissue. To further evaluate the role of GDNF on organization of the nigrostriatal system, single or double grafts of ventral mesencephalon (VM) and lateral ganglionic eminence (LGE) with mismatches in Gdnf genotypes were performed. The survival of single grafts was monitored utilizing magnetic resonance imaging (MRI) and cell survival and graft organization were evaluated with immunohistochemistry. The results revealed that the size of VM single grafts did not change over time independent of genotype, while the size of the LGE transplants was significantly reduced already at 2 weeks postgrafting when lacking GDNF. Lack of GDNF did not significantly affect the survival of tyrosine hydroxylase (TH)-positive neurons in single VM grafts. However, the survival of TH-positive neurons was significantly reduced in VM derived from Gdnf(+/+) when co-grafted with LGE from the Gdnf(-/-) tissue. In contrast, lack of GDNF in the VM portion of co-grafts had no effect on the survival of TH-positive neurons when co-grafted with LGE from Gdnf(+/+) mice. The TH-positive innervation of co-grafts was sparse when the striatal co-grafts were derived from the Gdnf(-/-) tissue while dense and patchy when innervating LGE producing GDNF. The TH-positive innervation overlapped with the organization of dopamine and cyclic AMP-regulated phosphoprotein-relative molecular mass 32,000 (DARPP-32)-positive neurons, that was disorganized in LGE lacking GDNF production. In conclusion, GDNF is important for a proper striatal organization and for survival of TH-positive neurons in the presence of the striatal tissue.
胶质细胞系源性神经营养因子（GDNF）对神经元具有神经保护和神经修复作用，并且GDNF在利用移植来创建Gdnf基因敲除（Gdnf(-/-)）组织的黑质纹状体微回路中，对多巴胺能神经元的维持起着重要作用。为了进一步评估GDNF在黑质纹状体系统组织中的作用，进行了腹侧中脑（VM）和外侧神经节隆起（LGE）的单移植或双移植，其Gdnf基因型不匹配。利用磁共振成像（MRI）监测单移植体的存活情况，并通过免疫组织化学评估细胞存活和移植体组织情况。结果显示，VM单移植体的大小不随时间变化，与基因型无关，而缺乏GDNF时，LGE移植体在移植后2周时大小就已显著减小。缺乏GDNF对单VM移植体中酪氨酸羟化酶（TH）阳性神经元的存活没有显著影响。然而，当来自Gdnf(+/+)的VM与来自Gdnf(-/-)组织的LGE共同移植时，TH阳性神经元的存活显著减少。相反，当与来自Gdnf(+/+)小鼠的LGE共同移植时，共同移植体VM部分缺乏GDNF对TH阳性神经元的存活没有影响。当纹状体共同移植体来自Gdnf(-/-)组织时，共同移植体的TH阳性神经支配稀疏，而当支配产生GDNF的LGE时则密集且呈斑片状。TH阳性神经支配与多巴胺和环磷酸腺苷调节磷酸蛋白相对分子质量32000（DARPP-32）阳性神经元的组织重叠，在缺乏GDNF产生的LGE中这种组织是紊乱的。总之，GDNF对于适当的纹状体组织以及在存在纹状体组织的情况下TH阳性神经元的存活很重要。
