We have previously observed that an axon-sparing injury to the developing striatum induced by the excitotoxin quinolinate results in a decrease in dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the adult. This decrease occurs in the absence of direct injury to the SNpc. As the striatum is a major target for the SNpc dopaminergic system, we have hypothesized that a decrease in the size of the striatal target during development may result in an induced regressive event in the SNpc, similar to what has been described for many developing neural systems with peripheral targets. We have examined by morphologic and biochemical means the time course and character of cell death in SN following a unilateral striatal lesion with quinolinate in immature rats. The striatal lesion is associated with an induced cell death event in the ipsilateral SN, observed first in SNpc and then in SN pars reticulata. The morphologic characteristics of the dying cells were typical of apoptosis. Immunostaining for tyrosine hydroxylase indicated that some of the apoptotic cells in the SNpc were dopaminergic. We conclude that developmental striatal excitotoxic injury is associated with induced apoptotic cell death in SN.
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机译:我们以前已经观察到,由兴奋毒素喹啉酸酯诱导的发育中的纹状体的轴突保留损伤导致成人黑质致密部(SNpc)多巴胺能神经元减少。这种减少发生在没有直接损害SNpc的情况下。由于纹状体是SNpc多巴胺能系统的主要靶标,因此我们假设发育过程中纹状体靶标的减小可能会导致SNpc中诱导的退行性事件,这与许多发育中的神经系统所描述的相似与外围目标。我们已经通过形态学和生化手段检查了未成熟大鼠单侧纹状体病变中喹啉酸酯引起的SN细胞死亡的时间过程和特征。纹状体病变与同侧SN中诱导的细胞死亡事件有关,首先在SNpc中观察到,然后在SN pars reticulata中观察到。垂死细胞的形态学特征是凋亡的典型特征。酪氨酸羟化酶的免疫染色表明SNpc中的某些凋亡细胞是多巴胺能的。我们得出结论,发育性纹状体兴奋性毒性损伤与SN中诱导的凋亡细胞死亡有关。
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