Excitatory Amino acid transporter expression in the essential tremor dentate nucleus and cerebellar cortex: A postmortem study
Excitatory Amino acid transporter expression in the essential tremor dentate nucleus and cerebellar cortex: A postmortem study
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DOI：
10.1016/j.parkreldis.2016.09.003
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发表时间：
2016-11-01
影响因子：
4.1
通讯作者：
Kuo, Sheng-Han
中科院分区：
文献类型：
--
作者：
Wang, Jie;Kelly, Geoffrey C.;Kuo, Sheng-Han
背景资料：全基因组关联研究揭示了特发性震颤（ET）和基因SLC 1A 2之间的联系，该基因编码兴奋性氨基酸转运蛋白2型（EAAT 2）。我们通过定量小脑齿状核中EAAT 2和EAAT 1水平来探索ET中的EAAT生物学，并扩展了我们先前对小脑皮质中EAAT 2水平的分析。目的：定量ET病例与对照组小脑齿状核和小脑皮质中EAAT 2和EAAT 1水平。我们使用免疫组化定量EAAT 2和EAAT 1水平在齿状核的发现队列的16例ET病例和16名对照。此外，我们在一个重复队列（61例ET病例，25例对照）中定量了齿状核中的EAAT 2水平。结果：在发现队列中，16例ET病例与16例对照相比，齿状EAAT 2水平高1.5倍（p = 0.007），但EAAT 1水平没有显着差异（p = 0.279）。在重复队列中，61例ET病例的齿状EAAT 2水平比25例对照高1.3倍（p = 0.022）。在发现和重复队列中，ET病例的小脑皮质EAAT 2水平比对照组低20%和40（相应的p值= 0.045和< 0.001）。EAAT 2在ET齿状核中的表达增强，与ET小脑皮质中EAAT 2水平的差异性降低相反，这可能反映了小脑核团维持兴奋-抑制平衡的一种代偿机制。(C)2016爱思唯尔有限公司版权所有
Background: Genome-wide association studies have revealed a link between essential tremor (ET) and the gene SLC1A2, which encodes excitatory amino acid transporter type 2 (EAAT2). We explored EAAT biology in ET by quantifying EAAT2 and EAAT1 levels in the cerebellar dentate nucleus, and expanded our prior analysis of EAAT2 levels in the cerebellar cortex.Objective: To quantify EAAT2 and EAAT1 levels in the cerebellar dentate nucleus and cerebellar cortex of ET cases vs. controls.Methods: We used immunohistochemistry to quantify EAAT2 and EAAT1 levels in the dentate nucleus of a discovery cohort of 16 ET cases and 16 controls. Furthermore, we quantified EAAT2 levels in the dentate nucleus in a replicate cohort (61 ET cases, 25 controls). Cortical EAAT2 levels in all 77 ET cases and 41 controls were quantified.Results: In the discovery cohort, dentate EAAT2 levels were 1.5-fold higher in 16 ET cases vs. 16 controls (p = 0.007), but EAAT1 levels did not differ significantly (p = 0.279). Dentate EAAT2 levels were 1.3-fold higher in 61 ET cases vs. 25 controls in the replicate cohort (p = 0.022). Cerebellar cortical EAAT2 levels were 20% and 40% lower in ET cases vs. controls in the discovery and the replicate cohorts (respective p values = 0.045 and < 0.001).Conclusion: EAAT2 expression is enhanced in the ET dentate nucleus, in contrast to differentially reduced EAAT2 levels in the ET cerebellar cortex, which might reflect a compensatory mechanism to maintain excitation-inhibition balance in cerebellar nuclei. (C) 2016 Elsevier Ltd. All rights reserved.