Motor deficits and altered striatal gene expression in aphakia (ak) mice.
Motor deficits and altered striatal gene expression in aphakia (ak) mice.
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无晶体眼 (ak) 小鼠的运动缺陷和纹状体基因表达改变。
DOI：
10.1016/j.brainres.2007.09.006
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
Zeiss,CarolineJ
中科院分区：
文献类型：
--
作者：
Singh,Bhupinder;Wilson,JeanH;Vasavada,HemaH;Guo,Zhenchao;Allore,HeatherG;Zeiss,CarolineJ
与患有帕金森病（PD）的人类一样，ak小鼠缺乏大部分黑质致密部（SNc）并经历纹状体去神经支配。本研究的目的是测试ak小鼠的运动异常是否随着时间的推移而进展，以及运动功能是否与纹状体转录组的时间改变有关。Ak和wt小鼠（28 ~ 180日龄）采用对黑质纹状体功能障碍敏感的范式进行测试。结果采用线性混合模型进行分析。Ak小鼠在各年龄段的旋转杆、平衡木、绳子、杆子和棉线测试中均显著低于对照组。ak小鼠的运动表现在出生后的前6个月保持不变，除了棉花丝测试外，ak小鼠的运动表现略有下降。在1月龄和6月龄的ak和wt小鼠中对19个多巴胺能、胆碱能、谷氨酰胺能和分解代谢基因进行背侧纹状体半定量RT-PCR检测。ak小鼠的前脑啡肽水平在两个年龄组中都有所升高。随着时间的推移，Drd1、3和4的表达水平下降，而Drd2的表达则增加。其他发现包括在ak小鼠中两个时间点的Chrnα6表达降低和VGluT1表达升高，仅在幼龄ak小鼠中AchE表达升高。结果证实，ak小鼠的运动能力在出生后的前6个月没有明显下降。它们的纹状体基因表达模式与多巴胺能去神经支配一致，并且随着时间的推移而改变，尽管运动表现相对不变。
Like humans with Parkinson's disease (PD), the ak mouse lacks the majority of the substantia nigra pars compacta (SNc) and experiences striatal denervation. The purpose of this study was to test whether motor abnormalities in the ak mouse progress over time, and whether motor function could be associated with temporal alterations in the striatal transcriptome. Ak and wt mice (28 to 180 days old) were tested using paradigms sensitive to nigrostriatal dysfunction. Results were analyzed using a linear mixed model. Ak mice significantly underperformed wt controls in rotarod, balance beam, string test, pole test and cotton shred tests at all ages examined. Motor performance in ak mice remained constant over the first 6 months of life, with the exception of the cotton shred test, in which ak mice exhibited marginal decline in performance. Dorsal striatal semi-quantitative RT-PCR for 19 dopaminergic, cholinergic, glutaminergic and catabolic genes was performed in 1- and 6-month-old groups of ak and wt mice. Preproenkephalin levels in ak mice were elevated in both age groups. Drd1, 3 and 4 levels declined over time, in contrast to increasing Drd2 expression. Additional findings included decreased Chrnα6 expression and elevated VGluT1 expression at both time points in ak mice and elevated AchE expression in young ak mice only. Results confirm that motor ability does not decline significantly for the first 6 months of life in ak mice. Their striatal gene expression patterns are consistent with dopaminergic denervation, and change over time, despite relatively unaltered motor performance.