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首页> 外文期刊>Brain research >Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in the cortex and globus pallidus of freely moving rats
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Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in the cortex and globus pallidus of freely moving rats

机译：HN2表达在STN中的减少有助于自由活动大鼠的皮质和苍白球的高压纺锤体异常

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摘要

Abnormal oscillation in the cortical-basal ganglia loop is involved in the pathophysiology of parkinsonism. High-voltage spindles (HVSs), one of the main type abnormal oscillations in Parkinson's disease, are regulated by dopamine D2-like receptors but not D1-like receptors. However, little is known about how dopamine D2-like receptors regulate HVSs and the role of hyperpolarization-activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation. We simultaneously recorded the local field potential (LFP) in globus pallidus (GP) and electrocorticogram (ECoG) in primary motor cortex (M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats. The expression of HCN2 and dopamine D2 receptor in the subthalamic nucleus (STN) was examined by immunochemical staining and Western blotting. We also tested the role of HCN2 in HVSs regulation by using pharmacological and shRNA methodology. We found that dopamine D2-like receptor agonists suppressed the increased HV5s in 6-OHDA lesioned rats. HCN2 was co-expressed with dopamine D2 receptor in the STN, and dopamine depletion decreased the expression of HCN2 as well as dopamine D2 receptor which contribute to the regulation of HVSs. HCN2 was down regulated by HCN2 shRNA, which thereby led to an increase in the HVSs in naive rats while HCN2 agonist reduced the HVSs in 6-OHDA lesioned rats. These results suggest that HCN2 in the STN is involved in abnormal oscillation regulation between M1 cortex and GP. (C) 2015 Elsevier B.V. All rights reserved.
机译：帕金森病的病理生理学涉及皮层-基底神经节环的异常振荡。高压纺锤体（HVS）是帕金森氏病的主要异常振动类型之一，受多巴胺D2样受体而不是D1样受体调节。但是，关于多巴胺D2样受体如何调节HVS以及超极化激活的环状核苷酸门控2（HCN2）在HVS调节中的作用知之甚少。我们同时记录了自由运动的6-羟基多巴胺（6-OHDA）病变或对照大鼠的苍白球（GP）和大脑皮层电图（ECoG）在主要运动皮层（M1）中的局部场电位（LFP）。通过免疫化学染色和蛋白质印迹法检测丘脑下丘脑核（STN）中HCN2和多巴胺D2受体的表达。我们还通过药理学和shRNA方法测试了HCN2在HVS调控中的作用。我们发现多巴胺D2样受体激动剂抑制6-OHDA损伤大鼠中增加的HV5s。 HCN2与多巴胺D2受体在STN中共表达，而多巴胺的消耗降低了HCN2和多巴胺D2受体的表达，这有助于调节HVS。 HCN2被HCN2 shRNA下调，从而导致幼稚大鼠的HVS增加，而HCN2激动剂减少了6-OHDA损伤大鼠的HVS。这些结果表明STN中的HCN2参与了M1皮质和GP之间的异常振荡调节。 （C）2015 Elsevier B.V.保留所有权利。

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