Burke R E, Macaya A, DeVivo D, Kenyon N, Janec E M
Department of Neurology, Columbia University, New York, NY 10032.
Neuroscience. 1992 Oct;50(3):559-69. doi: 10.1016/0306-4522(92)90447-a.
It has been shown that morphologic and biochemical presynaptic markers of dopaminergic terminals are preserved in a unilateral experimental model of neonatal hypoxic-ischemic injury to the striatum. As the substantia nigra is spared direct injury in this model, we anticipated that the number of tyrosine hydroxylase-positive dopaminergic neurons projecting to the striatum would also be normal. We have found, however, that following unilateral neonatal striatal injury the number of ipsilateral tyrosine hydroxylase-positive neurons is decreased, as is the mean area of the substantia nigra pars compacta. The decrease in neurons is correlated with the decrease in striatal size (r = 0.7, P = 0.01). Neuron loss is most pronounced in the substantia nigra pars reticulata, where it is 50%. Calbindin-positive neurons in the dorsal tier of the substantia nigra pars compacta appear to be preserved. We also examined effects on the nigra following a neonatal excitotoxic striatal lesion made with quinolinic acid. We observed a decrease in the number of substantia nigra tyrosine hydroxylase-positive neurons in the absence of direct nigral injury, and the decrease was closely correlated with reductions in striatal area (r = 0.91, p < 0.01). While there are a number of possible explanations for these observations, one major possibility is that there has been a reduction in tyrosine hydroxylase-positive neurons due to a diminution in developmental target-derived trophic support from the striatum. If striatum-derived trophic support plays a role in the developmental regulation of substantia nigra neuron number, then abnormalities in this supportive relationship may play a role in the loss of these neurons in some animal models of developmental nigral degeneration, and some forms of human parkinsonism.
研究表明，在单侧新生儿纹状体缺氧缺血性损伤的实验模型中，多巴胺能终末的形态学和生化突触前标志物得以保留。由于在该模型中黑质未受到直接损伤，我们预计投射到纹状体的酪氨酸羟化酶阳性多巴胺能神经元数量也会正常。然而，我们发现，单侧新生儿纹状体损伤后，同侧酪氨酸羟化酶阳性神经元数量减少，黑质致密部的平均面积也减小。神经元数量的减少与纹状体大小的减小相关（r = 0.7，P = 0.01）。神经元损失在黑质网状部最为明显，达50%。黑质致密部背层的钙结合蛋白阳性神经元似乎得以保留。我们还研究了用喹啉酸造成新生儿兴奋性毒性纹状体损伤后对黑质的影响。我们观察到在没有黑质直接损伤的情况下，黑质酪氨酸羟化酶阳性神经元数量减少，且这种减少与纹状体面积的减小密切相关（r = 0.91，p < 0.01）。虽然对这些观察结果有多种可能的解释，但一个主要的可能性是，由于来自纹状体的发育靶点衍生的营养支持减少，酪氨酸羟化酶阳性神经元数量减少。如果来自纹状体的营养支持在黑质神经元数量的发育调节中起作用，那么这种支持关系的异常可能在某些发育性黑质变性动物模型和某些形式的人类帕金森病中这些神经元的损失中起作用。
