Yurek D M, Seroogy K B
Department of Surgery/Neurosurgery, University of Kentucky College of Medicine, Lexington 40536, USA.
J Comp Neurol. 2000 Jul 31;423(3):462-73. doi: 10.1002/1096-9861(20000731)423:3<462::aid-cne9>3.0.co;2-u.
This study examined the expression of neurotrophins and neurotrophin receptors in the lesion/transplanted striatum at four different time points after transplantation. The ventral mesencephalic region was dissected from a single rat fetus at embryonic day 14 (E14) and implanted into the denervated striatum of rats with unilateral 6-hydroxydopamine lesions. Transplanted rats were killed at 1, 2, 3, or 4 weeks after transplantation surgery and the brains subsequently prepared for semiquantitative in situ hybridization analysis of neurotrophin and neurotrophin trk receptors. Hybridization of cRNA probes for trkB or trkC showed a time-dependent reduction within the transplant during the first 4 weeks after transplantation; hybridization of brain-derived neurotrophic factor or tyrosine hydroxylase mRNA probes within the transplant did not change significantly during the same posttransplantation period. Hybridization of the trkB mRNA probe in host striatum adjacent to the transplant was significantly higher than probe hybridization in the corresponding region of the intact striatum during the first 2 weeks after transplantation, but by the 3rd and 4th week, probe hybridization in the denervated/transplanted and intact striatum were the same. Lesioned animals without transplants maintained higher trkB mRNA probe hybridization in the denervated striatum than in the intact striatum at the same postlesion time points suggesting that lesioned/transplanted animals show a normalization of trkB mRNA probe hybridization. Hybridization of the trkC mRNA probe in the lesioned/transplanted striatum was significantly lower than that observed in the intact striatum 4 weeks after transplantation; however, at this same time point we observed a similar reduction of trkC probed hybridization in lesioned animals without transplants. The results of the study show dynamic neurotrophic activity occurring within the transplant and host tissue during the first month of transplant development.
本研究检测了移植后四个不同时间点损伤/移植纹状体内神经营养因子和神经营养因子受体的表达。在胚胎第14天（E14）从一只大鼠胎儿中分离出腹侧中脑区域，并将其植入单侧6-羟基多巴胺损伤大鼠的失神经纹状体内。移植大鼠在移植手术后1、2、3或4周处死，随后将大脑制备用于神经营养因子和神经营养因子trk受体的半定量原位杂交分析。trkB或trkC的cRNA探针杂交显示，移植后前4周内移植体内呈时间依赖性降低；在同一移植后时期，移植体内脑源性神经营养因子或酪氨酸羟化酶mRNA探针的杂交没有显著变化。在移植后前2周，移植旁宿主纹状体内trkB mRNA探针的杂交显著高于完整纹状体相应区域的探针杂交，但到第3周和第4周，失神经/移植纹状体和完整纹状体内的探针杂交相同。在相同的损伤后时间点，未移植的损伤动物失神经纹状体内的trkB mRNA探针杂交高于完整纹状体，这表明损伤/移植动物的trkB mRNA探针杂交出现了正常化。损伤/移植纹状体内trkC mRNA探针的杂交在移植后4周显著低于完整纹状体内观察到的杂交；然而，在这个相同的时间点，我们在未移植的损伤动物中观察到trkC探针杂交也有类似的降低。研究结果表明，在移植发育的第一个月内，移植体和宿主组织内发生了动态神经营养活性。
