NEURODEGENERATION AND NEUROPROTECTION OF MESOSTRIATAL DOPAMINE SYSTEM

为了验证多巴胺能变性的氧化应激假说，使用神经化学和免疫组织化学方法，比较了具有脑中氧代谢异常的zitter突变大鼠和作为对照的Sprague-Dawley大鼠之间的中纹状体多巴胺神经元系统的年龄相关变化。随着年龄的增长，zitter大鼠尾壳核、延髓核和嗅结节内多巴胺含量显著降低，并低于相应年龄对照组。在zitter大鼠中，多巴胺的减少在尾壳核比在延髓核和嗅结节更突出。还观察到zitter大鼠尾壳核中酪氨酸羟化酶免疫反应阳性纤维的特征性下降。在背外侧尾壳核，酪氨酸羟化酶免疫反应纤维减少观察到的基质样区域，而在腹内侧尾壳核的减少发生在补丁样地区。在尾壳核和延髓核中观察到以肿胀的静脉曲张和成簇的纤维为特征的酪氨酸羟化酶免疫反应纤维的变性，并且在尾壳核中观察到正常酪氨酸羟化酶免疫反应纤维的损失。因此，终末区多巴胺的耗竭与轴突变性有关。然而，有没有退化的酪氨酸羟化酶免疫反应纤维在嗅结节在任何检查的年龄，但减少酪氨酸羟化酶免疫反应纤维和多巴胺的含量后，注意到在嗅结节4个月的年龄。

To test the oxidant stress hypothesis of dopaminergic degeneration, age-related changes in the mesostriatal dopamine neuron system were compared between zitter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry and immunohistochemistry. Dopamine content in the caudate-putamen, nucleus accumbens and olfactory tubercle of zitter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls. In the zitter rats, the reduction of dopamine was more prominent in the caudate-putamen than in the nucleus accumbens and olfactory tubercle. A characteristic decline of tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen of the zitter rat was also observed. In the dorsolateral caudate-putamen, reduction of tyrosine hydroxylase-immunoreactive fibers was observed in the matrix-like area, whereas in the ventromedial caudate-putamen the reduction occurred in the patch-like areas. Degeneration of tyrosine hydroxylase-immunoreactive fibers which was characterized by swollen varicosities and clustered fibers was observed in the caudate-putamen and nucleus accumbens and preceded loss of normal tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen. Thus, the depletion of dopamine in the terminal areas is related to axonal degeneration. However, there was no degenerative tyrosine hydroxylase-immunoreactive fibers in the olfactory tubercle at any examined age, but reductions of tyrosine hydroxylase-immunoreactive fibers and dopamine contents were noted in the olfactory tubercle after four months-of-age.