MPTP对小鼠中脑α-突触核蛋白线粒体表达和线粒体形态改变的影响  

Effects of MPTP on α-synuclein expression and morphology of mitochondria in mouse midbrain

作　　者：朱敏[1,2] 唐红敏[1] 余平波 李文伟[1,2] 

机构地区：[1]复旦大学附属中山医院中西医结合神经生理病理实验室,上海200032 [2]复旦大学神经病学研究所,上海200032

出　　处：《神经解剖学杂志》2014年第4期396-402,共7页Chinese Journal of Neuroanatomy

基　　金：上海市科技支撑项目(12401901003);上海市自然科学基金(10ZR1406100)

摘　　要：目的:观察MPTP对中脑黑质神经元线粒体表达α-突触核蛋白及线粒体形态改变的影响。方法:运用腹腔注射MPTP诱导C57/BL小鼠中脑黑质神经元损伤,以生理盐水腹腔注射小鼠作为对照组。运用线粒体纯化结合Western Blot分析线粒体α-突触核蛋白的水平,运用免疫组织化学标记结合激光共聚焦方法观察线粒体结构的改变。运用MPP+干预原代培养的多巴胺能神经元,观察线粒体形态的改变。结果:MPTP可以诱导小鼠中脑线粒体α-突触核蛋白的水平升高,并导致线粒体出现碎片化,碎片化的线粒体结构与α-突触核蛋白共定位。运用MPP+处理原代培养的中脑腹侧神经元,发现MPP+可以选择性地诱导多巴胺能神经元的线粒体碎片化。定量研究显示:多巴胺能神经元经MPP+处理后,线粒体的长度显著降低(P<0.01)。结论:MPTP可以在体诱导多巴胺能神经元的线粒体碎片化,线粒体α-突触核蛋白水平的升高可能与其碎片化密切相关。Objective： To investigate the effects of 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） on mitochondrial α-synuclein levels and morphology within substantia nigra （SN） of midbrain. Methods： C57/BL mice were injected with MPTP to produce Parkinsonism models, and the animals were injected with saline in control group. The protein levels of α-synuclein in mitochondria were analyzed by Western Blot, and mitochondrial morphology was observed using confocal laser microscopy. Mitochondrial morphology was also evaluated in primary dopaminergic neurons exposed to MPP^＋. Results： The results showed that MPTP led to up-regulation of α-synuclein in mitochondria and fragmented mitochondria which co-localized with α-synuclein in neurons within SN after exposed to MPTP. After exposed to MPP^＋ for 12 h, ventral neurons from ventral midbrain showed that significant mitochondrial fragmentation was seen in almost each remaining tyrosine hydroxylase（TH） immodnoveactive（THir） cell, but not in non-THir cells; and quantified data showed that mitochondrial length is significantly decreased in THir cells （P 〈 0.01% ） rather than in non-THir cells when compared with control ceils. Conclusion： These data suggest that MPTP could induce mitochondrial fragmentation in vivo, and there is a close relationship between α-synuclein level and magnitude of mitochondrial fragmentation.

关 键 词：MPTP Α-突触核蛋白 帕金森病 线粒体碎片化 

分 类 号：R742.5[医药卫生—神经病学与精神病学]