Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.
Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.
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DOI：
10.1016/j.brainres.2017.12.002
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发表时间：
2018-02-01
期刊：
影响因子：
2.9
通讯作者：
Ciucci MR
中科院分区：
文献类型：
--
作者：
Kelm-Nelson CA;Brauer AFL;Barth KJ;Lake JM;Sinnen MLK;Stehula FJ;Muslu C;Marongiu R;Kaplitt MG;Ciucci MR
帕金森病（PD）是一种复杂的神经退行性疾病，影响全球近1000万人，运动技能明显受损。然而，运动缺陷的发生和进展以及这些缺陷的神经相关性知之甚少。我们使用与人类PD具有表型相似性的PD遗传小鼠模型（Pink 1-/-）来研究早发性感觉运动缺陷的表现。我们假设这种小鼠模型将显示早期发声和粗大运动功能障碍，这将是渐进的性质。在2、3、4、5和6月龄时，对Pink 1 −/−小鼠与野生型（WT）对照小鼠进行了比较。为了量化缺陷进展，分析了超声发声和自发运动活动（柱体试验和杆试验）。虽然有些变化，但总的来说，与WT小鼠相比，Pink 1 −/−小鼠产生的简单叫声明显更多，强度降低，周期叫声的百分比也更大。然而，基因型之间的任何超声波呼叫类型的持续时间，带宽或峰值频率没有显着差异。与WT相比，Pink 1 −/−小鼠在肢体运动技能方面表现出明显的障碍，在圆柱体测试中后肢步数、前肢步数以及后肢和后肢着地数较少。此外，Pink 1 −/−小鼠在杆测试期间需要更长的时间来转弯和穿越。免疫组织化学染色显示，基因型之间黑质酪氨酸羟化酶（TH）阳性细胞的数量或纹状体TH染色密度没有显着差异。这些数据表明，Pink 1 −/−小鼠模型可能有助于在没有黑质纹状体多巴胺丢失的情况下定义PD的早期运动生物标志物。
In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1 −/−), with phenotypic similarities to human PD, to investigate the manifestation of early-onset sensorimotor deficits. We hypothesized this mouse model would show early vocalization and gross motor dysfunction that would be progressive in nature. Pink1 −/− mice, compared to wild type (WT) controls, were evaluated at 2, 3, 4, 5, and 6 months of age. To quantify deficit progression, ultrasonic vocalizations and spontaneous locomotor activity (cylinder test and pole test) were analyzed. Although somewhat variable, in general, Pink1 −/− mice produced significantly more simple calls with reduced intensity as well as a larger percentage of cycle calls compared to WT counterparts. However, there were no significant differences in duration, bandwidth, or peak frequency for any of the ultrasonic call types between genotypes. Pink1 −/− mice showed a significant impairment in limb motor skills with fewer hindlimb steps, forelimb steps, and rears and lands in the cylinder test compared to WT. Additionally, Pink1 −/− mice took significantly longer to turn and traverse during the pole test. Immunohistochemical staining showed no significant difference in the number of tyrosine hydroxylase (TH) positive cells in the substantia nigra or density of TH staining in the striatum between genotypes. These data suggest the Pink1 −/− mouse model may be instrumental in defining early motor biomarkers of PD in the absence of nigrostriatal dopamine loss.
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影响因子：
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通讯作者：
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