Quinn Leann P, Perren Marion J, Brackenborough Kim T, Woodhams Peter L, Vidgeon-Hart Martin, Chapman Helen, Pangalos Menelas N, Upton Neil, Virley David J
Neurology & GI CEDD, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
J Neurosci Methods. 2007 Aug 15;164(1):43-9. doi: 10.1016/j.jneumeth.2007.03.021. Epub 2007 Apr 6.
A beam-walking apparatus has been evaluated for its ability to detect motor impairments in mice acutely treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg, s.c., single or double administration). Mice subjected to MPTP lesioning showed deficits in motor performance on the beam-walking task, for up to 6 days post-MPTP administration, as compared to saline-treated controls. In addition, MPTP-treated mice were detected to have a marked depletion in striatal dopamine levels and a concomitant reduction in substantia nigra (SN) tyrosine hydroxylase (TH) immunoreactivity, at 7 days post-MPTP administration, indicative of dopaminergic neuronal loss. Pre-administration of the potent MAO-B inhibitor R-(-)-deprenyl at 3 or 10 mg/kg, 30 min, s.c, significantly inhibited the MPTP-induced reduction in SN TH-immunoreactivity, striatal dopamine depletions and impairments in mouse motor function. The data described in the present study provides further evidence that functional deficits following an acute MPTP dosing schedule in mice can be quantified and are related to nigro-striatal dopamine function.
一种横梁行走装置已被评估其检测用多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP，30mg/kg，皮下注射，单次或两次给药）急性处理的小鼠运动损伤的能力。与生理盐水处理的对照组相比，接受MPTP损伤的小鼠在MPTP给药后长达6天的横梁行走任务中运动表现存在缺陷。此外，在MPTP给药后7天，检测到MPTP处理的小鼠纹状体多巴胺水平显著降低，同时黑质（SN）酪氨酸羟化酶（TH）免疫反应性降低，表明多巴胺能神经元丢失。在MPTP给药前30分钟皮下注射3或10mg/kg的强效单胺氧化酶B（MAO-B）抑制剂R-（-）-司来吉兰，可显著抑制MPTP诱导的SN TH免疫反应性降低、纹状体多巴胺耗竭以及小鼠运动功能损伤。本研究中描述的数据进一步证明，小鼠急性MPTP给药方案后的功能缺陷可以被量化，并且与黑质纹状体多巴胺功能有关。
