Sortwell C E, Camargo M D, Pitzer M R, Gyawali S, Collier T J
Department of Neurological Sciences, Research Center for Brain Repair, Rush-Presbyterian-St. Luke's Medical Center, Suite 200, 2242 West Harrison Street, Chicago, Illinois, 60612, USA.
Exp Neurol. 2001 May;169(1):23-9. doi: 10.1006/exnr.2001.7644.
The survival rate of dopamine (DA) neurons in mesencephalic grafts to young adult rats is poor, estimated at 5-20%, and even poorer in grafts to the aged striatum. Grafted cells die in young adult rats during the first 4 days after implantation. The present study was undertaken to determine whether the decreased survival of DA neurons in grafts to aged rats is (1) due to additional cell death during the immediate postgrafting interval or (2) due to protracted cell loss during longer postgrafting intervals. We compared survival rates of tyrosine hydroxylase-immunoreactive (THir) neurons in cell suspension grafts to young adult (3 months) and aged (24 months) male Fischer 344 rats at 4 days and 2 weeks after transplantation. At 4 days after grafting, mesencephalic grafts within the aged rat striatum contain approximately 25% of the number of THir neurons in the same mesencephalic cell suspension grafted to young adult rats. This corroborates the decreased survival of grafted DA neurons we have demonstrated previously at 10 weeks postgrafting. THir neurons in grafts to the intact striatum possessed a significantly shorter "long axis" than their counterparts on the lesioned side. No significant differences in the number of apoptotic nuclear profiles or total alkaline phosphatase staining between mesencephalic grafts to young and aged rats were detectable at 4 days postgrafting. In summary, the present study indicates that the exaggerated cell death of grafted DA neurons that occurs following implantation to the aged striatum occurs during the immediate postgrafting interval, timing identical to that documented for young adult hosts.
移植到年轻成年大鼠中的中脑移植物中多巴胺(DA)神经元的存活率很低,估计为5%-20%,移植到老年纹状体中的移植物存活率更低。移植的细胞在植入后的头4天内在年轻成年大鼠中死亡。本研究旨在确定移植到老年大鼠中的移植物中DA神经元存活率降低是(1)由于移植后即刻间隔期额外的细胞死亡,还是(2)由于移植后较长间隔期内细胞的持续丢失。我们比较了移植后4天和2周时,细胞悬液移植物中酪氨酸羟化酶免疫反应性(THir)神经元在年轻成年(3个月)和老年(24个月)雄性Fischer 344大鼠中的存活率。移植后4天,老年大鼠纹状体内的中脑移植物中THir神经元数量约为移植到年轻成年大鼠的相同中脑细胞悬液中THir神经元数量的25%。这证实了我们之前在移植后10周所证明的移植DA神经元存活率降低的情况。移植到完整纹状体的移植物中的THir神经元的“长轴”明显短于损伤侧的对应神经元。移植后4天,在移植到年轻和老年大鼠的中脑移植物之间,凋亡核轮廓数量或总碱性磷酸酶染色没有显著差异。总之,本研究表明,移植到老年纹状体后发生的移植DA神经元过度细胞死亡发生在移植后即刻间隔期,这与年轻成年宿主的情况一致。