Quantitative Analysis of Catecholamines in the Pink1 -/- Rat Model of Early-onset Parkinson's Disease.
Quantitative Analysis of Catecholamines in the Pink1 -/- Rat Model of Early-onset Parkinson's Disease.
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DOI：
10.1016/j.neuroscience.2018.02.027
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发表时间：
2018-05-21
期刊：
影响因子：
3.3
通讯作者：
Ciucci MR
中科院分区：
文献类型：
--
作者：
Kelm-Nelson CA;Trevino MA;Ciucci MR
与Pink 1基因纯合突变相关的帕金森病（PD）与黑质纹状体多巴胺耗竭和广泛的感觉运动缺陷有关。在人类和PD动物模型中，并非所有感觉运动缺陷都是左旋多巴反应性的。我们假设运动、肢体控制和声音交流行为的潜在机制包括其他病理。在这里，Pink 1 −/−大鼠接受口服剂量的左旋多巴治疗，并测量肢体运动和声音交流行为。左旋多巴显着改善运动的某些方面，但没有提高超声发声强度或频率。分析纹状体（SR）、黑质（SN）和蓝斑（LC）中的儿茶酚胺浓度，以检验行为缺陷与蛋白质水平改变相关的假设。与野生型对照组相比，Pink 1 −/−动物的SR和SN中的多巴胺浓度没有差异。Pink 1 −/−动物SN中的去甲肾上腺素浓度显著增加。此外，在LC中观察到的去甲肾上腺素浓度降低与早期PD包括脑干中去甲肾上腺素能损失的假设一致，并且与Pink 1 −/−动物LC中儿茶酚-O-甲基转移酶表达的显著增加一致。皮尔逊相关性表明，时间的增加，以遍历锥形平衡木显着相关的纹状体多巴胺的减少。超声发声复杂度与LC去甲肾上腺素浓度呈正相关。这些数据支持不断发展的假设，即脑干中神经基质和早发性去甲肾上腺素能机制的差异可能有助于Pink 1 −/−大鼠的发病机制。
Parkinson disease (PD) related to homozygous mutations in the Pink1 gene is associated with nigrostriatal dopamine depletion and a wide range of sensorimotor deficits. In humans and animal models of PD, not all sensorimotor deficits are levodopa-responsive. We hypothesized that the underlying mechanisms of locomotion, limb control, and vocal communication behavior include other pathologies. Here, Pink1 −/− rats were treated with an oral dose of levodopa and limb motor and vocal communication behaviors were measured. Levodopa significantly improved some aspects of locomotion but did not improve ultrasonic vocalization intensity or frequency. Catecholamine concentrations in the striatum (SR), substantia nigra (SN), and locus coeruleus (LC) were analyzed to test the hypothesis that behavioral deficits would correlate to altered protein levels. There were no differences in dopamine concentrations in the SR and SN of Pink1 −/− animals compared to wildtype controls. There was a significant increase in norepinephrine concentration in the SN of Pink1 −/− animals. Moreover, an observed decrease in norepinephrine concentrations in the LC is consistent with the hypothesis that early-stage PD includes noradrenergic loss in the brainstem, and is congruent with a significant increase in catechol-O-methyltransferase expression in the LC of Pink1 −/− animals. Pearson correlations showed that increases in time to traverse a tapered balance beam are significantly associated with reductions in striatal dopamine. Ultrasonic vocalization complexity was positively correlated with LC norepinephrine concentrations. These data support the evolving hypothesis that differences in neural substrates and early-onset noradrenergic mechanisms in the brainstem may contribute to pathogenesis in the Pink1 −/− rat.
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影响因子：
8.6
作者：
BurleighJacobs, A;Horak, FB;Obeso, JA
通讯作者：
Obeso, JA
影响因子：
5.3
作者：
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通讯作者：
Chesselet, MF
影响因子：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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