NEURODEGENERATION AND NEUROPROTECTION OF MESOSTRIATAL DOPAMINE SYSTEM

中纹状体多巴胺系统的神经变性和神经保护

• 批准号: 10680707
• 负责人: UEDA Shuichi
• 金额: $ 1.98万
• 依托单位: Dokkyo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680707/
• 关键词: Dopamine; Parkinson's disease; Superoxide; Oxydant stress; Mutant rat; Degeneration; Serotonin; Striatum

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.

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。

项目成果

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Yoshimoto, K.：“年龄和乙醇对大鼠伏核中多巴胺和血清素释放的影响。”生理学

Okuda,K.: "Evidence for degeneration of monoaminergic fibers in the spinal cord of zitter mutant rats."Acta Histo. Cyto.. 32. 341-344 (1999)

Okuda,K.：“zitter 突变大鼠脊髓中单胺能纤维变性的证据。”Acta Histo。

Ueda,S.: "Age-related dopamine deficiency in the mesostriatal dopamine of zitter mutant rats : Regional fiber vulnerability in the striatum and olfactory tubercle"Neuroscience. 95. 389-398 (2000)

Ueda,S.：“zitter 突变大鼠中纹状体多巴胺与年龄相关的多巴胺缺乏：纹状体和嗅结节的区域纤维脆弱性”神经科学。

Yoshimoto, K.: "Treating neonatal rats with 6-hydroxydopamine induced an increase in voluntary alcohol consumption."Alcohol. Clin. Exp. Res.. 23. 2S-6S (1999)

Yoshimoto, K.：“用 6-羟基多巴胺治疗新生大鼠会导致自愿饮酒量增加。”酒精。

Ueda,S.: "Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: Regional fiber vulnerability in the striatum and the olfactory tubercle."Neuroscience. 95. 389-398 (2000)

Ueda,S.：“zitter 突变大鼠中纹状体多巴胺系统中与年龄相关的多巴胺缺乏：纹状体和嗅结节的区域纤维脆弱性。”神经科学。