Strömberg I, Humpel C
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Brain Res Dev Brain Res. 1995 Feb 16;84(2):215-24. doi: 10.1016/0165-3806(94)00172-v.
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, expresses potential effects on survival and outgrowth from dopaminergic neurons in ventral mesencephalon. In this study we have examined the expression of BDNF mRNA and its high affinity trkB receptor mRNA in the nigrostriatal system after grafting to the anterior chamber of the eye. The BDNF mRNA expression has been compared to the dopaminergic innervation of striatum as revealed by tyrosine hydroxylase (TH) immunohistochemistry and the development of D1 and D2 subtypes of the dopamine receptor mRNAs. Ventral mesencephalon and striatum anlage were either co-grafted or grafted alone and evaluated 2 weeks (immature grafts) or 6 weeks (mature grafts) after transplantation. In situ hybridization for BDNF revealed a positive signal over large neurons in the ventral mesencephalic grafts with an increased silver grain density in the mature grafts. The striatal grafts were negative for BDNF mRNA at both time points evaluated, but in situ hybridization for trkB truncated mRNA revealed increased silver grain density in both the ventral mesencephalic grafts and striatum, with a patchy appearance. The D1 and D2 mRNAs were expressed in a patchy pattern in the striatum both in single grafts and when co-implanted with ventral mesencephalon at both time points evaluated. Often the patches of D1 mRNA did not overlap with the D2 mRNA patches. TH-immunohistochemistry revealed positive neurons in all ventral mesencephalic grafts and a dense patchy innervation of the striatal co-grafts. In conclusion, the trkB truncated mRNA and the dopamine receptor mRNAs were expressed in the striatal graft independent of the contact to a ventral mesencephalic transplant and the dopaminergic input, and BDNF mRNA expression in the ventral mesencephalic transplants was independent of the contact to its striatal target.
脑源性神经营养因子（BDNF）是神经营养因子家族的一员，对中脑腹侧多巴胺能神经元的存活和生长具有潜在影响。在本研究中，我们检测了移植到眼前房后黑质纹状体系统中BDNF mRNA及其高亲和力trkB受体mRNA的表达。将BDNF mRNA表达与酪氨酸羟化酶（TH）免疫组织化学显示的纹状体多巴胺能神经支配以及多巴胺受体mRNA的D1和D2亚型的发育情况进行了比较。中脑腹侧和纹状体原基要么共同移植，要么单独移植，并在移植后2周（未成熟移植物）或6周（成熟移植物）进行评估。BDNF的原位杂交显示中脑腹侧移植物中的大神经元有阳性信号，成熟移植物中的银颗粒密度增加。在评估的两个时间点，纹状体移植物的BDNF mRNA均为阴性，但trkB截短mRNA的原位杂交显示中脑腹侧移植物和纹状体中的银颗粒密度均增加，呈斑片状外观。在评估的两个时间点，无论是单移植还是与中脑腹侧共同植入时，D1和D2 mRNA在纹状体中均呈斑片状表达。通常，D1 mRNA的斑块与D2 mRNA的斑块不重叠。TH免疫组织化学显示所有中脑腹侧移植物中有阳性神经元，纹状体共同移植物中有密集的斑片状神经支配。总之，trkB截短mRNA和多巴胺受体mRNA在纹状体移植物中的表达独立于与中脑腹侧移植体的接触和多巴胺能输入，中脑腹侧移植体中BDNF mRNA的表达独立于与其纹状体靶标的接触。
