Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson's disease
Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson's disease
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DOI：
10.1016/j.physbeh.2009.04.021
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发表时间：
2009-08-04
影响因子：
2.9
通讯作者：
Song, Cai
中科院分区：
文献类型：
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作者：
Luchtman, Dirk W.;Shao, Di;Song, Cai
在C57 BL/6小鼠中比较了1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的帕金森病（PD）模型的三种常见给药方案对行为、纹状体和纹状体外神经传递以及脑细胞因子的影响，以阐明方案之间在这些变量上的差异。急性方案：旋转棒性能和开放领域梳理下降。纹状体多巴胺（DA）耗尽，但DA营业额增加。纹状体去甲肾上腺素（NA）、额叶皮质5-羟色胺（5-HT）和中脑NA和DA均耗竭。亚急性方案：与急性方案相反，旋转杆和杆测试性能。和开阔地的梳理都有所增加。纹状体DA耗尽，但DA营业额增加超过急性方案。纹状体5-HT周转率和皮质NA也增加。慢性方案：Rotorod性能受损，但旷场距离增加。纹状体DA被严重耗尽，DA和5-HT营业额大幅增加。纹状体5-HT、额叶皮质NA和DA以及皮质DA均耗竭。促炎细胞因子白细胞介素（IL）-1 β，肿瘤坏死因子（TNF）-α，干扰素（IFN）-γ，粒细胞巨噬细胞集落刺激因子（GM-CSF）和IL-10仅在慢性方案中增加，但这些细胞因子被发现在所有方案中与纹状体DA周转类似。该研究表明，方案之间的行为差异的存在可能取决于所使用的行为测试的类型以及方案中多巴胺能、非多巴胺能和纹状体外神经传递受影响的程度。该研究还为相对较新的慢性MPTP/丙磺舒模型的有效性提供了额外的证据。总之，结果表明，应仔细预先考虑给药方案。(C)2009 Elsevier Inc. All rights reserved.
Three common dosing regimens of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of Parkinson's disease (PD) were compared in C57BL/6 mice on behavior, striatal and extra-striatal neurotransmission, and brain cytokines, to clarify the differences between regimens on these variables. Acute regimen: Rotorod performance and open field grooming were decreased. Striatal dopamine (DA) was depleted, but DA turnover increased. Striatal noradrenalin (NA), frontal cortex serotonin (5-HT) and midbrain NA and DA were all depleted. Sub-acute regimen: Opposite to the acute regimen, rotorod and pole test performance. and open field grooming were all increased. Striatal DA was depleted, but DA turnover was increased more than in the acute regimen. Striatal 5-HT turnover and cortical NA were increased as well. Chronic regimen: Rotorod performance was impaired, but open field distance moved increased. Striatal DA was severely depleted and DA and 5-HT turnover strongly increased. Striatal 5-HT, frontal cortex NA and DA, and cortical DA were all depleted. Pro-inflammatory cytokines interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-10 were only increased in the chronic regimen, but these cytokines were found to be similarly related to striatal DA turnover in all regimens. The study demonstrated that the presence of behavioral differences between regimens may depend on the type of behavioral tests used and the extent to which dopaminergic, nondopaminergic and extra-striatal neurotransmission are affected in the regimens. The study also provided additional evidence for the validity of the relatively new chronic MPTP/probenecid model. In all, the results suggested that dosing regimens should be carefully pre-considered. (C) 2009 Elsevier Inc. All rights reserved.