Altered expression of dopamine receptors in cholinergic motoneurons of the hypoglossal nucleus in a 6-OHDA-induced Parkinson's disease rat model
Altered expression of dopamine receptors in cholinergic motoneurons of the hypoglossal nucleus in a 6-OHDA-induced Parkinson's disease rat model
复制标题
6-OHDA 诱导的帕金森病大鼠模型舌下核胆碱能运动神经元中多巴胺受体表达的改变
DOI：
10.1016/j.bbrc.2014.08.104
复制
发表时间：
2014
影响因子：
3.1
通讯作者：
Zhu JX
中科院分区：
文献类型：
--
作者：
Zhou L;Wang ZY;Lian H;Song HY;Zhang YM;Zhang XL;Fan RF;Zheng LF;Zhu JX
帕金森病 (PD) 是一种常见的神经退行性疾病，通常与舌头运动减弱有关。然而，黑质（SN）退化的多巴胺能神经元与舌功能障碍之间的联系仍不清楚。在本研究中，我们使用双标记免疫荧光、蛋白质印迹和半定量逆转录和聚合酶链反应（SqRT-PCR）研究了舌下核（HN）胆碱能运动神经元中多巴胺受体1（D1）和多巴胺受体2（D2）的定位及其表达的变化，这些大鼠接受双侧SN（6-OHDA）显微注射老鼠）。结果显示，大量胆碱乙酰转移酶免疫反应性 (ChAT-IR) 神经元分布在整个 HN 中，并且几乎所有 ChAT-IR 运动神经元也是 D1-IR 和 D2-IR。在 ChAT-IR、D1-IR 或 D2-IR 体细胞附近观察到多种酪氨酸羟化酶 (TH)-IR 谱，其模式不均匀，表明存在有效的多巴胺能神经支配。在6-OHDA大鼠中，SN中的TH免疫反应性显着降低，但食物残渣增加并且跑步机占用时间缩短。在HN中，TH和D2的蛋白表达增加，而ChAT和D1的蛋白表达减少。在 mRNA 水平上也观察到了类似的模式。目前的研究表明，多巴胺可能通过与 HN 中的 D1 和 D2 结合来调节胆碱能神经元的活性。 6-OHDA大鼠HN中ChAT、TH、D1和D2表达的变化可能与PD舌运动受损有关。这些发现应进一步调查。
Parkinson’s disease (PD) is a common neurodegenerative disorder that is often associated with weak tongue motility. However, the link between the degenerated dopaminergic neurons in the substantia nigra (SN) and lingual dysfunction remains unclear. In the present study, we investigated the localization of dopamine receptor 1 (D1) and dopamine receptor 2 (D2) and alternations in their expression in cholinergic motoneurons of the hypoglossal nucleus (HN) using double-label immunofluorescence, Western blotting and semi-quantitative reverse transcription and polymerase chain reaction (SqRT–PCR) in rats that received microinjections of 6-hydroxydopamine bilaterally into the SN (6-OHDA rats). The results revealed that a large population of choline acetyltransferase immunoreactive (ChAT-IR) neurons was distributed throughout HN and that almost all of the ChAT-IR motoneurons were also D1-IR and D2-IR. Several tyrosine hydroxylase (TH)-IR profiles were observed in a nonuniform pattern near the ChAT-IR, D1-IR or D2-IR somas, suggesting potent dopaminergic innervation. In the 6-OHDA rats, TH immunoreactivity in the SN was significantly decreased, but food residue was increased and treadmill occupancy time was shortened. In the HN, protein expression of TH and D2 was increased, whereas that of ChAT and D1 was decreased. A similar pattern was observed in mRNA levels. The present study suggests that dopamine may modulate the activity of cholinergic neurons via binding with D1 and D2 in the HN. Changes in the expression of ChAT, TH, D1 and D2 in the HN of 6-OHDA rats might be associated with the impaired tongue motility in PD. These findings should be further investigated.