Modeling a sensitization stage and a precipitation stage for Parkinson's disease using prenatal and postnatal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration.
Modeling a sensitization stage and a precipitation stage for Parkinson's disease using prenatal and postnatal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration.
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DOI：
10.1016/j.neuroscience.2010.04.080
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发表时间：
2010-09-01
期刊：
影响因子：
3.3
通讯作者：
Charlton, C. G.
中科院分区：
文献类型：
--
作者：
Muthian, G.;Mackey, V.;King, J.;Charlton, C. G.
关键词：
特发性帕金森病（PD）是一种成熟和老年人的神经退行性疾病。由于所有老年人不会发展PD，可能存在与衰老期间基底神经节上的压力配对的诱发条件，以产生PD的症状。在这个项目中，我们使用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）来检验特发性PD的致敏阶段和沉淀阶段的假设。为了诱导致敏阶段，在妊娠第8-12天用MPTP（10 mg/kg/天）处理妊娠C57 BL/6 J小鼠以靶向新生的胎儿黑质纹状体多巴胺神经元。对于沉淀阶段，对3个月大的后代施用MPTP 7天，以模拟老化期间发生的变化。测定仔鼠体重、运动能力、纹状体多巴胺及其代谢产物的HPLC含量和酪氨酸羟化酶（TH）的Western blot。暴露于产前MPTP的后代表现出较低的出生体重，最终恢复。产前MPTP也减少了10- 30%的运动活动，纹状体TH 38%，多巴胺14%，高香草酸16.5%和3-甲氧基酪胺66%。出生后的MPTP是更有效的在产前MPTP暴露的后代。MPTP在10、20和30 mg/kg剂量下，在产前PBS小鼠中使纹状体TH降低9.4%、48.6%和82.4%，在产前MPTP组中降低48%、78.7%和92.7%。更重要的是，出生后MPTP在10 mg/kg时对产前PBS后代中的DA、DOPAC、HVA和3-MT表现出轻微影响，在产前MPTP小鼠中表现出69.9%、80.0%、48.4%和65.4%的降低。该研究可能确定一种新的PD模型，结果表明，一些特发性PD病例可能具有胎儿基础，其中早期发生轻微的黑质纹状体损伤，并且PD症状随后通过黑质纹状体的恶化变化而沉淀，这不会在具有正常黑质纹状体系统的个体中引起症状。
Idiopathic Parkinson’s disease (PD) is a neurodegenerative disorder of mature and older individuals. Since all aged individuals do not develop PD, predisposing conditions may exist that pair with the stress placed on the basal ganglia during aging to produce the symptoms of PD. In this project we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to test the hypothesis that a sensitization stage and a precipitating stage underlie idiopathic PD. To induce the sensitization stage, pregnant C57BL/6J mice were treated with MPTP (10mg/kg/dy) during gestation days 8–12 to target the emerging fetal nigrostriatal dopamine neurons. For the precipitating stage, the 3-months old offspring were administered MPTP for 7 days, to simulate the changes that occur during aging. The weights and motor activity of the offspring, HPLC striatal dopamine and its metabolites and Western blot for tyrosine hydroxylase (TH) were determined. Offspring exposed to prenatal MPTP showed lower birth weights that eventually recovered. Prenatal MPTP also reduced motor activity by 10–30%, striatal TH by 38%, dopamine by 14%, homovanillic acid by 16.5% and 3-methoxytyramine by 66%. The postnatal MPTP was more potent in the prenatal MPTP-exposed offspring. MPTP at 10, 20 and 30mg/kg, dose-relatedly, reduced striatal TH by 9.4%, 48.6% and 82.4% in the prenatal-PBS mice and by 48%, 78.7% and 92.7% in the prenatal-MPTP groups. More importantly, postnatal MPTP at 10mg/kg that showed slight effects on DA, DOPAC, HVA and 3-MT in the prenatal-PBS offspring, showed 69.9%, 80.0%, 48.4% and 65.4% reductions in the prenatal-MPTP mice. The study may identify a new model for PD, and the outcome suggests that some cases of idiopathic PD may have a fetal basis in which early subtle nigrostriatal impairments occurred and PD symptoms are precipitated later by deteriorating changes in the nigrostriatum, that would not caused symptoms in individuals with normal nigrostriatal system.
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影响因子：
4.2
作者：
Muthian, Gladson;Raikwar, Himanshu P.;Bright, John J.
通讯作者：
Bright, John J.
影响因子：
3.4
作者：
Kanthasamy, AG;Kitazawa, M;Anantharam, V
通讯作者：
Anantharam, V
DOI：
10.1111/j.1600-0773.1992.tb00575.x
发表时间：
1992-12-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
BAGETTA, G;CORASANITI, MT;STEPHENSON, JD
通讯作者：
STEPHENSON, JD
影响因子：
2.5
作者：
PERRY, TL;YONG, VW;JONES, K
通讯作者：
JONES, K
DOI：
10.1016/1055-8330(95)90015-2
发表时间：
1995-09-01
期刊：
NEURODEGENERATION
影响因子：
--
作者：
JACKSONLEWIS, V;JAKOWEC, M;PRZEDBORSKI, S
通讯作者：
PRZEDBORSKI, S