Kozlovsky Nitsan, Scarr Elizabeth, Dean Brian, Agam Galila
Stanley Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheva, Israel.
Schizophr Res. 2006 Apr;83(2-3):173-7. doi: 10.1016/j.schres.2005.12.843. Epub 2006 Feb 7.
Calcineurin (CaN), also designated as protein phosphatase 2B, is a major Ca2+/calmodulin-binding protein in the brain and the only serine/threonine phosphatase under the control of Ca2+/calmodulin. CaN activity has been implicated in downstream regulation of dopaminergic signal transduction and in NMDA receptor-dependent synaptic plasticity. Thus, it serves as a point of convergence for the abnormalities of these two neurotransmitter systems in schizophrenia. The aim of the present study was to determine if levels of CaN were altered in two schizophrenia- and CaN-related brain regions--the dorsolateral prefrontal cortex and hippocampus from subjects with schizophrenia compared to that in tissue from age and sex matched controls. CaN protein levels were measured by Western-blot analysis in samples from 15 schizophrenia patients vs. 15 control subjects. No significant differences in CaN protein levels were found either in the prefrontal cortex or in the hippocampus of schizophrenia patients compared to matched control subjects. Our result of lack of difference does not support the concept that brain CaN levels are a pathophysiological factor in this disorder. Further studies with antibodies against specific CaN catalytic subunit isoforms (presently unavailable) are required to resolve this issue.
钙调神经磷酸酶(CaN),也被称为蛋白磷酸酶2B,是大脑中一种主要的Ca2+/钙调蛋白结合蛋白,也是唯一受Ca2+/钙调蛋白调控的丝氨酸/苏氨酸磷酸酶。CaN的活性与多巴胺能信号转导的下游调节以及NMDA受体依赖性突触可塑性有关。因此,它是精神分裂症中这两种神经递质系统异常的一个汇聚点。本研究的目的是确定与年龄和性别匹配的对照组相比,精神分裂症患者的两个与精神分裂症和CaN相关的脑区——背外侧前额叶皮质和海马体中CaN的水平是否发生改变。通过蛋白质免疫印迹分析测量了15例精神分裂症患者和15例对照受试者样本中的CaN蛋白水平。与匹配的对照受试者相比,精神分裂症患者的前额叶皮质或海马体中CaN蛋白水平均未发现显著差异。我们缺乏差异的结果不支持脑CaN水平是该疾病病理生理因素的观点。需要进一步使用针对特定CaN催化亚基异构体的抗体(目前尚无)进行研究来解决这个问题。