GluN2B protein deficits in the left, but not the right, hippocampus in schizophrenia.
GluN2B protein deficits in the left, but not the right, hippocampus in schizophrenia.
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DOI：
10.1186/s12888-014-0274-z
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发表时间：
2014-10-08
期刊：
影响因子：
4.4
通讯作者：
Newell KA
中科院分区：
文献类型：
--
作者：
Geddes AE;Huang XF;Newell KA
越来越多的证据表明，NMDA受体的功能和亚基组成的改变与精神分裂症的病理生理学相关。GluN2B蛋白是NMDA受体的结构和功能亚基，越来越多的证据表明它在NMDA受体介导的认知功能中起关键作用。海马体在认知功能中起着关键作用，研究表明该区域的偏侧海马体功能障碍可能导致精神分裂症患者中观察到的认知缺陷。本研究，第一次，调查GluN2B蛋白和结合密度在左，右海马的20名精神分裂症患者相比，20个匹配的对照。齿状回的20名精神分裂症患者和20名对照受试者，匹配的年龄，死后的时间，和pH值，从新南威尔士州组织资源中心，澳大利亚。每组包括左侧大脑半球和右侧大脑半球各10个齿状回。通过免疫印迹法测量GluN2B蛋白密度。使用GluN2B拮抗剂[3H]艾芬地尔测量GluN2B结合密度。协方差分析，影响数据的人口统计学变量的协变，被用来测试精神分裂症和对照组之间的统计学意义。Pearson相关性用于确定GluN2B蛋白和结合密度与人口统计学和临床变量（包括终生抗精神病药物暴露）的相关性。与对照组相比，精神分裂症受试者左半球的GluN2B蛋白水平降低了43%（p = 0.012）。与对照组相比，精神分裂症受试者右半球的GluN2B蛋白水平没有差异。根据诊断或半球，[3H]艾芬地尔结合无差异。GluN2B指标与终生抗精神病药物暴露之间无相关性。我们的研究结果提供了第一个证据，GluN2蛋白异常的海马在精神分裂症，突出了海马偏侧化在这种疾病。我们认为这种缺陷可能导致患者出现认知功能障碍。这些发现为开发以GluN2B亚基为靶点的治疗药物，作为治疗精神分裂症，特别是认知功能障碍的新疗法提供了初步支持。
Increasing evidence indicates that alterations to the function and subunit composition of the glutamatergic NMDA receptor are associated with the pathophysiology of schizophrenia. The GluN2B protein is a structural and functional subunit of the NMDA receptor, with a growing body of evidence indicating it plays a critical role in cognitive functions mediated by the NMDA receptor. The hippocampus plays a key role in cognitive function, with studies suggesting lateralised glutamatergic dysfunction in this region may contribute to the cognitive deficits observed in schizophrenia patients. The present study, for the first time, investigated GluN2B protein and binding density in the left and right hippocampus of 20 schizophrenia subjects compared to 20 matched controls. The dentate gyrus of 20 schizophrenia and 20 control subjects, matched for age, post-mortem interval, and pH, was obtained from the NSW Tissue Resource Centre, Australia. Each group consisted of dentate gyrus from the left hemisphere (n = 10) and right hemisphere (n = 10). GluN2B protein density was measured via immunoblotting. GluN2B binding density was measured using the GluN2B antagonist, [3H] Ifenprodil. Analyses of covariance, covarying for demographic variables that influenced the data, were used to test for statistical significance between schizophrenia and control groups. Pearson’s correlations were used to determine the association of GluN2B protein and binding density with demographic and clinical variables, including lifetime antipsychotic drug exposure. GluN2B protein levels were decreased by 43% in the left hemisphere of schizophrenia subjects compared to controls (p = 0.012). There was no difference in GluN2B protein levels in the right hemisphere of schizophrenia subjects compared to controls. There were no differences in [3H] Ifenprodil binding according to diagnosis or hemisphere. There were no associations between GluN2B measures and lifetime antipsychotic drug exposure. Our findings provide the first evidence of GluN2 protein abnormalities in the hippocampus in schizophrenia, highlighting the hippocampal lateralisation in this disorder. We suggest this deficit could contribute to the cognitive dysfunctions that arise in patients. These findings provide preliminary support for the development of therapeutics that target the GluN2B subunit, as a novel therapy for schizophrenia, especially the cognitive dysfunctions.
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影响因子：
3.4
作者：
Law, AJ;Weickert, CS;Harrison, PJ
通讯作者：
Harrison, PJ
DOI：
10.1016/0922-4106(94)90211-9
发表时间：
1994-01-01
期刊：
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION
影响因子：
--
作者：
HASHIMOTO, K;MANTIONE, CR;LONDON, ED
通讯作者：
LONDON, ED
影响因子：
17.7
作者：
Ibrahim, HM;Hogg, AJ;Meador-Woodruff, JH
通讯作者：
Meador-Woodruff, JH
DOI：
10.1073/pnas.0830996100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Fukaya, M;Kato, A;Watanabe, M
通讯作者：
Watanabe, M
影响因子：
3.6
作者：
Fumagalli, Fabio;Frasca, Angelisa;Riva, Marco Andrea
通讯作者：
Riva, Marco Andrea