Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra.
Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra.
复制标题
死后精神分裂症黑质神经递质合成和释放的蛋白质标记。
DOI：
10.1038/npp.2016.164
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Roberts,RosalindaC
中科院分区：
文献类型：
--
作者：
Schoonover,KirstenE;McCollum,LesleyA;Roberts,RosalindaC
黑质（SN）向大脑提供最大的多巴胺能输入，投射到纹状体（抗精神病药物的主要作用部位），并接收GABA能和多巴胺能输入。本研究使用蛋白质印迹分析比较酪氨酸羟化酶（TH），谷氨酸脱羧酶（GAD 67）和囊泡谷氨酸转运蛋白（vGLUT 1和vGLUT 2）在精神分裂症受试者（n= 13）和匹配对照（n= 12）的死后人SN的蛋白质水平。作为初步分析，精神分裂症组被细分为（1）治疗状态：停药（n= 4）或用药（n= 9）;或（2）治疗反应：治疗抵抗（n= 5）或治疗反应（n= 4）。合并精神分裂症组TH和GAD 67蛋白水平高于对照组（分别增加69.6%，P= 0.01和19.5%，P= 0.004）。当按药物状态细分时，在药物治疗受试者中发现这些增加（TH 88.3%，P= 0.008; GAD 67 40.6%，P= 0.003）。相比之下，未服药的精神分裂症受试者的vGLUT 2水平高于对照组（增加28.7%，P= 0.041），但服药的精神分裂症受试者和对照组之间的vGLUT 2水平相似。治疗抵抗的受试者具有显著高于对照组的TH和GAD 67水平（分别增加121.0%，P= 0.0003和58.7%，P= 0.004）。这些数据表明，增加多巴胺和GABA传输的SN在精神分裂症，与治疗和反应的潜在关系。
The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n= 13) and matched controls (n= 12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n= 4) or on medication (n= 9); or (2) treatment response: treatment resistant (n= 5) or treatment responsive (n= 4). The combined schizophrenia group had higher TH and GAD67 protein levels than controls (an increase of 69.6%, P= 0.01 and 19.5%, P= 0.004, respectively). When subdivided by medication status, these increases were found in the on-medication subjects (TH 88.3%, P= 0.008; GAD67 40.6%, P= 0.003). In contrast, unmedicated schizophrenia subjects had higher vGLUT2 levels than controls (an increase of 28.7%, P= 0.041), but vGLUT2 levels were similar between medicated schizophrenia subjects and controls. Treatment-resistant subjects had significantly higher TH and GAD67 levels than controls (an increase of 121.0%, P= 0.0003 and 58.7%, P= 0.004, respectively). These data suggest increases in dopamine and GABA transmission in the SN in schizophrenia, with a potential relation to treatment and response.