Calprotectin in microglia from frontal cortex is up-regulated in schizophrenia: evidence for an inflammatory process?
Calprotectin in microglia from frontal cortex is up-regulated in schizophrenia: evidence for an inflammatory process?
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DOI：
10.1111/j.1460-9568.2006.05219.x
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发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
Everall, Ian P.
中科院分区：
文献类型：
--
作者：
Foster, Russell;Kandanearatchi, Apsara;Everall, Ian P.
精神分裂症与许多病理变化有关，包括特定蛋白质水平的改变。钙卫蛋白是S100家族的一种新的36 kDa钙结合蛋白，似乎是炎症的非特异性标志物。钙卫蛋白以前未在脑组织中进行过研究。从精神分裂症、双相情感障碍、重性抑郁症受试者和对照组的前额叶皮层中获得布罗德曼9区的死后脑组织样本。通过ELISA测定钙卫蛋白水平。为了确定细胞定位，进行免疫细胞化学和荧光双标记分析。将外源性钙卫蛋白加入到视黄酸分化的人SH-SY 5 Y神经母细胞瘤细胞培养物中，以研究钙卫蛋白的作用机制。钙卫蛋白在所有样品中均检测到，并且注意到平均水平在精神分裂症脑中最高（P < 0.05），而在对照组中最低。在双相情感障碍和重度抑郁症中水平居中。外源性钙卫蛋白似乎以剂量依赖性方式诱导SH-SY 5 Y细胞培养中的树突状延伸。发现钙卫蛋白定位于小胶质细胞。这些发现表明，大脑中钙卫蛋白水平的增加可能反映了炎症过程，这在主要精神疾病的发病机制中发挥了作用。此外，钙卫蛋白可能影响树突的可塑性。
Schizophrenia is associated with a number of pathological changes, including alterations in levels of specific proteins. Calprotectin is a novel 36 kDa calcium-binding protein of the S100 family and appears to be a nonspecific marker of inflammation. Calprotectin has not previously been investigated in brain tissue. Samples of post-mortem brain tissue from Brodmann area 9 were obtained from prefrontal cortex from subjects with schizophrenia, bipolar affective disorder, major depression, and from controls. Calprotectin levels were determined by ELISA. To determine cellular localization, immunocytochemical and fluorescent double-labelling analyses were performed. Exogenous calprotectin was added to retinoic acid-differentiated human SH-SY5Y neuroblastoma cell cultures in order to investigate mechanisms of action of calprotectin. Calprotectin was detectable in all samples, and mean levels were noted to be highest in schizophrenic brains (P < 0.05) and lowest in controls. Levels were intermediate in bipolar affective disorder and major depression. Exogenous calprotectin appeared to induce dendritic extension in SH-SY5Y cell culture in a dose-dependent manner. Calprotectin was found to be localized to microglia. These findings suggest that increased levels of calprotecitn in the brain may reflect inflammatory processes, which play a role in the pathogenesis of major psychiatric disorders. Furthermore, calprotectin may influence dendritic plasticity.