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Models for experimental PD

(2007-09-05 09:17:18)
标签:

健康/保健

帕金森病

实验动物

mptp小鼠

猴模型

果蝇模型

分类: 帕金森病
 
l     关于帕金森病的实验动物,目前国内外比较公认的有 MPTP小鼠、猴模型, 6-OH DOPA大鼠、猴模型、果蝇模型等。由于经济方面的原因,国内大部分实验室多采用较为经济的大、小鼠进行造模,果蝇模型组在国外多见;猴模型由于涉及到动物保护、试验经费等原因,多用来做临床前的行为学观察!
    下面是有关大、小鼠PD模型的应用原则,仅供大家参考,有关离体细胞模型将在下一章节讨论!
 
lOne of the best models for generating experiment is the administration of MPTP , which causes a specific loss of SNpc neurons identical to that seen in PD.Exposure to MPTP has similar effects in many vertebrate species, including man and mouse.MPTP is metabolized by glial MAO-b to MPP+. MPP+ is transported into neurons through  the DAT where it interferes with Complex respiration.
lOnce in cells, MPP+ is sequestered into vesicles  by VMAT2, which may provide some cellular protection against this toxin.Thus ,the relative expression of DAT and VMAT2 within a neuron may determine its potential for survival from an exogenous toxin. Molecular Brain Research 134 (2005)170-179
l
 
The MPTP  mouse model as well as methamphetamine, rotenone and paraquat models, however, are used  more  to evaluate the mechanisms of neurodegeneration or the biochemical parameters correlated to neuroprotective effects of drugs rather than in the study of behavioral parameters, as behavioral changes and hypomotility (运动减少)are not consistently observed in these models( Anna R, et al. Behavioral Pharmacology 2006 ).
lInterestingly, rats are not sensitive to MPTP toxicity possibly due to their high capacity to sequestrate MPTP in vesicles( Staal RG, et al. Pharmacol Exp 2000).      

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