Acetylcholine receptor subunit expression in Huntington's disease mouse muscle.

Acetylcholine receptor subunit expression in Huntington's disease mouse muscle.
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DOI:
10.1016/j.bbrep.2021.101182
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发表时间:
2021-12
影响因子:
2.7
通讯作者:
Talmadge RJ
Talmadge RJ
中科院分区:
其他
文献类型:
--
作者:
Simpson B;Rich MM;Voss AA;Talmadge RJ

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亨廷顿病(HD)会导致神经损伤和肌肉功能障碍,包括较小的神经肌肉接头(NMJ)。这项研究评估了烟碱型乙酰胆碱受体(NAChR)亚单位在R6/2小鼠HD模型肌肉中的表达水平。根据我们之前发现的R6/2小鼠NMJ尺寸减小的结果,我们假设R6/2小鼠的肌肉与野生型(WT)小鼠相比也会显示出nAChR亚单位的表达模式改变。因此,利用qRT-PCR技术对R6/2和WT小鼠肌肉中nAChR亚基的mRNA水平进行了定量研究。WT小鼠的失神经肌肉作为nAChR表达变化的阳性对照。虽然在R6/2肌肉中nAChR亚单位的表达发生了一些变化,但表达水平与WT非常相似。然而,与WT相比,R6/2肌肉中nAChR亚单位-ε(ChRYNE)的表达显著降低。这项研究表明,在R6/2小鼠肌肉中,nAChR亚单位的表达只发生了很小的变化,而chrne表达的减少可能与R6/小鼠的NMJ大小减少有关。亨廷顿病(R6/2)小鼠肌肉中nAChR亚单位的表达仅有轻微变化。主要变化是nAChR-ε亚单位表达减少。相反,正如预期的那样,去神经支配导致了nAChR亚单位的重大变化。最后,在R6/2小鼠骨骼肌中,nAChR-γ亚单位的表达在疾病的任何阶段都没有变化。
Huntington's disease (HD) causes neurological impairments, as well as muscle dysfunction, including smaller neuromuscular junctions (NMJs). This study assessed the expression levels of the subunits of the nicotinic acetylcholine receptor (nAChR) in muscles of the R6/2 mouse model of HD. Based on our previous findings of reduced NMJ size in R6/2 mice, it was hypothesized that muscles from R6/2 mice would also show an altered expression pattern of nAChR subunits compared to wild-type (WT) mice. Therefore, the mRNA levels of nAChR subunits were quantified in R6/2 and WT mouse muscles using qRT-PCR. Denervated muscles from WT mice served as positive controls for alterations in nAChR expression. Although some changes in nAChR subunit expression occurred in R6/2 muscles, the expression levels closely resembled WT. However, the expression of nAChR subunit-ε (Chrne) was significantly decreased in R6/2 muscles relative to WT. This study demonstrates that only minor changes in nAChR subunit expression occurs in R6/2 mouse muscles and that reduction in Chrne expression may be related to a reduction in NMJ size in R6/mice. Huntington's Disease(R6/2) mouse muscles showed only minor alterations in the expression of nAChR subunits. The primary change being a reduction in the expression of nAChR-ε subunit. In contrast and as expected, denervation caused major changes in nAChR subunits. Lastly, R6/2 mouse skeletal muscle showed no changes in nAChR-γ subunit expression at any disease stage.
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