MONOAMINES IN PSYCHIATRY DISORDERS--MPTP MODEL

这项研究将检验MPTP的效果 (1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine)关于单胺能系统的研究 3月龄和21月龄黑质纹状体多巴胺能系统的研究 C57BL/6雄性小鼠。本项目中建议的研究将提供 足够的试点数据来检验这样的假设：(A)MPTP治疗在 成年C57BL/6小鼠除了能改变其他单胺能系统外，还能改变其他单胺系统 黑质纹状体多巴胺能系统，以及(B)21个月龄C57BL/6小鼠， 已经表现出黑质纹状体多巴胺能和部位的恶化 蓝斑去甲肾上腺素能系统作为自然衰老过程的一部分， 与3月龄小鼠相比，小鼠对MPTP更敏感。为了测试这些 假设，我们将追求以下具体目标：(1)3岁和3岁的小鼠 将测试21个月龄之间的剂量-反应关系 MPTP治疗和改变的单胺系统，包括黑质纹状体 和非黑质纹状体多巴胺能、去甲肾上腺素和5-羟色胺能系统 应用荧光组织化学技术对儿茶酚胺进行定位 胞体数量和神经末梢密度的定量，酪氨酸 CALL羟基酶免疫细胞化学计算机细胞形态计量学研究 黑质和腹侧被盖区DA神经元的计数， 多巴胺-B-羟基酶免疫细胞化学定位NE神经元 蓝斑及其主要脑区神经末梢的密度 投影场和高性能的微穿孔神经化学 液相色谱-电化学检测(LCEC)，(2) 相同的处理方案和实验设计，处理和对照 小鼠将被允许在最后一次死亡后存活2周或2个月 注射用MPTP治疗慢性阻塞性肺疾病的近期和远期疗效 以上设计的参数。这些研究应该会产生足够的试点 确定MPTP神经毒性作为模型的有用性的数据 帕金森氏病不仅对解剖学和神经化学造成损害 黑质纹状体系统，但也对其他已知的单胺系统造成损害 在帕金森氏症患者和精神病患者中受到影响 精神错乱。

This study will examine the effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) on monoaminergic systems in addition to the nigrostriatal dopaminergic system in 3 and 21 month old C57BL/6 male mice. The studies proposed in this project will provide sufficient pilot data to test the hypothesis that (a) MPTP treatment in adult C57BL/6 mice alters other monoaminergic systems in addition to the nigrostriatal dopaminergic system, and (b) 21 month old C57BL/6 mice, who already demonstrate deterioration of nigrostriatal dopaminergic and locus coeruleus noradrenergic system as part of the natural aging process, are more sensitive to MPTP treatment than 3 months old mice. To test these hypotheses, we will pursue the following specific aims: (1) mice at 3 and 21 months of age will be tested for a dose-response relationship between MPTP treatment and altered monoamine systems, including both nigrostriatal and non-nigrostriatal dopaminergic, noradrenergic and serotonergic systems using fluorescence histochemistry for catecholamine localization and quantitation of cell body numbers and nerve terminal densities, tyrosine hydroxylase immunocytochemistry with computerized cytomorphometry for call counts of DA neurons in substantia nigra and the ventral tegmental area, and dopamine-B-hydroxylase immunocytochemistry for NE neurons in locus coeruleus as well as the density of nerve terminals in their major projection fields, and micropunch neurochemistry with high performance liquid chromatography with electrochemical detection (LCEC), (2) following the same treatment protocol and experimental design, treated and control mice will be allowed to survive for 2 weeks or 2 months after the last injection to examine the short and long-term effects of MPTP treatment on the parameters designed above. These studies should yield sufficient pilot data to determine the usefulness of MPTP neurotoxicity as model for Parkinson's disease not only for anatomical and neurochemical damage to the nigrostriatal system, but also for damage to other monoamine systems known to be affected in humans with Parkinson's disease and in Psychiatric disorders.