Broadbelt Kevin, Ramprasaud Andrew, Jones Liesl B
Lehman College, CUNY, Department of Biological Sciences, 250 Bedford Park Blvd., Bronx, NY 10468, USA.
Schizophr Res. 2006 Oct;87(1-3):6-14. doi: 10.1016/j.schres.2006.04.028. Epub 2006 Jun 22.
Schizophrenia is a complex and poorly understood neuropsychiatric disorder. Much research has begun to implicate the prefrontal cortex in the disease. Using immunocytochemistry we determined if neurogranin, a protein found in dendrites, spines and cell bodies and an upstream regulator of calcium was altered in areas 9 and 32 of schizophrenic prefrontal cortex. We examined its expression in pyramidal cells in layers III and V. Tissues from 7 controls and 7 schizophrenics (from our original MAP2 study, Jones, L., Johnson, N., Byne, W., 2002. Alterations in MAP2 staining in area 9 and 32 of schizophrenic prefrontal cortex. Psych. Res. 114, 137-148) matched for age, sex and postmortem interval were examined. Using area fraction analysis we quantified the immunostaining. Additionally, we counted the number of positively stained pyramidal cells in the same 7 pairs. Neurogranin immunostaining was dramatically reduced in both layers III (72%) and V (50%) in area 9. In area 32 there was a more modest reduction in both layers III (36%) and V (40%). There was no difference in either brain region or layer in the density of positively stained pyramidal cells. These data confirm mounting evidence suggesting dendritic loss in the prefrontal cortex and suggest that the loss of protein does not appear to be due to a change in the number of cells producing the protein but rather in the amount of protein being produced. Additionally, these data suggest that the loss of neurogranin may alter the calcium-calmodulin dependent pathways due to its role as a regulator of calmodulin suggesting a link between structural and functional alterations of the pyramidal cells in the prefrontal cortex.
精神分裂症是一种复杂且了解甚少的神经精神疾病。许多研究已开始表明前额叶皮质与该疾病有关。我们运用免疫细胞化学方法，确定了在精神分裂症患者前额叶皮质的9区和32区中，一种存在于树突、棘突和细胞体中的蛋白质——神经颗粒素，作为钙的上游调节因子，是否发生了改变。我们检测了其在Ⅲ层和Ⅴ层锥体细胞中的表达。研究了来自7名对照者和7名精神分裂症患者（取自我们最初的微管相关蛋白2研究，琼斯，L.，约翰逊，N.，拜恩，W.，2002年。精神分裂症患者前额叶皮质9区和32区微管相关蛋白2染色的改变。《精神病学研究》114卷，第137 - 148页）的组织，这些组织在年龄、性别和死后间隔时间上相互匹配。我们运用面积分数分析法对免疫染色进行了定量。此外，我们统计了同一7对样本中阳性染色锥体细胞的数量。9区的Ⅲ层（72%）和Ⅴ层（50%）中神经颗粒素免疫染色显著减少。在32区，Ⅲ层（36%）和Ⅴ层（40%）的减少幅度较小。阳性染色锥体细胞的密度在两个脑区的任何一层中均无差异。这些数据证实了越来越多的证据表明前额叶皮质存在树突丢失，并表明蛋白质的丢失似乎并非由于产生该蛋白质的细胞数量变化，而是由于所产生蛋白质的量的变化。此外，这些数据表明，由于神经颗粒素作为钙调蛋白调节剂的作用，其丢失可能会改变钙 - 钙调蛋白依赖性途径，这表明前额叶皮质锥体细胞的结构和功能改变之间存在联系。
