Consequences of manganese administration for striatal dopamine and motor behavior in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed C57BL/6 mice
Consequences of manganese administration for striatal dopamine and motor behavior in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed C57BL/6 mice
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DOI：
10.1177/0960327112469043
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发表时间：
2013-08-01
影响因子：
2.8
通讯作者：
Klein, B. G.
中科院分区：
文献类型：
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作者：
Dodd, C. A.;Bloomquist, J. R.;Klein, B. G.
环境化合物可能是帕金森病病因学的重要因素。锰促进帕金森病的流行病学和实验证据是模棱两可的。本工作解决了锰对1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱导的C57BL/6小鼠毒性的少数研究中的方法学问题。雄性退役种鼠在第1、4、7天皮下注射氯化锰(MnCl2)0或100 mg/kg，第8天皮下注射MPTP 0或20 mg/kg，存活至第15或22天。在处死当天，检查水平(横格)和垂直(直立)开阔场地运动、游泳、握力和握力疲劳。用高效液相色谱法分析纹状体中的多巴胺和3，4-二羟基苯乙酸(DOPAC)。MPTP引起纹状体多巴胺(48.8%)和DOPAC(38.1%)的主效应降低，而MnCl2和MnCl2(2)与MPTP的相互作用没有主效应。然而，MnCl2和MPTP对网格交叉、饲养和握力的影响之间存在调制交互作用。有趣的是，这些相互作用降低了单独归因于这两种化合物的行为缺陷的严重性。对于饲养和握力，MnCl(2)xMPTP的相互作用取决于存活时间。在纹状体多巴胺和DOPAC缺乏这种相互作用的情况下，MnCl(2)xMPTP相互作用对这些行为的机制本质仍有待阐明。
Environmental compounds may be important contributors to Parkinson's disease etiology. Epidemiological and experimental evidence for the facilitation of parkinsonism by manganese is equivocal. This work addressed methodological concerns in the few studies of manganese modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in C57BL/6 mice. Male, retired breeder mice received 0 or 100mg/kg of manganese chloride (MnCl2; subcutaneously on days 1, 4 and 7) and 0 or 20mg/kg of MPTP (intraperitoneally on day 8) and survived up to day 15 or 22. On the day of sacrificing, horizontal (grid crossing) and vertical (rearing) open field movement, swimming, grip strength and grip fatigue were examined. Striata were analyzed for dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) using high-performance liquid chromatography. MPTP produced a main effect decrease in striatal dopamine (48.8%) and DOPAC (38.1%), but there was no main effect of MnCl2 or MnCl(2)xMPTP interaction. However, modulatory interactions were observed between the effects of MnCl2 and MPTP for grid crossing, rearing and grip strength. Interestingly, these interactions reduced the severity of behavioral deficits attributable to either of these compounds alone. For rearing and grip strength, the MnCl(2)xMPTP interaction was dependent upon survival time. The mechanistic nature of the MnCl(2)xMPTP interaction upon these behaviors, in the absence of such an interaction for striatal dopamine and DOPAC, remains to be clarified.