Apoptosis in substantia nigra following developmental striatal excitotoxic injury.
Apoptosis in substantia nigra following developmental striatal excitotoxic injury.
复制标题
发育性纹状体兴奋性毒性损伤后黑质的细胞凋亡。
DOI：
10.1073/pnas.91.17.8117
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发表时间：
1994
影响因子：
11.1
通讯作者：
Burke,RE
中科院分区：
文献类型：
--
作者：
Macaya,A;Munell,F;Gubits,RM;Burke,RE
我们以前观察到，由喹啉类兴奋性毒素引起的对发育中的纹状体的轴突保护损伤导致成人黑质致密部(SNPC)内多巴胺能神经元的减少。这种减少发生在没有对SNPC造成直接伤害的情况下。由于纹状体是SNPC多巴胺能系统的主要靶点，我们假设在发育过程中纹状体靶点的大小减小可能导致SNPC的诱发退行性事件，类似于许多具有外周靶点的发育中的神经系统的描述。我们用形态和生化方法观察了幼年大鼠单侧纹状体喹诺酮损毁后黑质细胞死亡的时程和特征。纹状体损害与同侧SN的诱导细胞死亡事件有关，首先在SNPC观察到，然后在SN网状部观察到。死亡细胞的形态特征为典型的细胞凋亡。酪氨酸羟化酶免疫组织化学染色显示，SNPC内部分凋亡细胞为多巴胺能细胞。我们的结论是，发育中纹状体兴奋性毒性损伤与诱导黑质细胞凋亡有关。
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.