Vawter M P, Thatcher L, Usen N, Hyde T M, Kleinman J E, Freed W J
Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Mol Psychiatry. 2002;7(6):571-8. doi: 10.1038/sj.mp.4001158.
Several studies suggest that decreased expression of presynaptic proteins may be characteristic of schizophrenia. We examined one such protein, synapsin, in schizophrenia and bipolar disorder. Samples of hippocampal tissue from controls (n = 13), patients with schizophrenia (n = 16), or bipolar disorder (n = 6), and suicide victims (n = 7) were used. The membrane and cytosolic fractions were analyzed by Western immunoblotting for synapsin using an antibody that detects synapsin Ia, IIa, and IIIa proteins. Synaptophysin was also measured for comparison. Total synapsin was decreased significantly in patients with schizophrenia (P = 0.034) and in bipolar disorder (P = 0.00008) as compared to controls. The synapsin/synaptophysin ratios were decreased in schizophrenia and bipolar disorder, and additionally in suicide victims (P = 0.014). Age, postmortem interval, percentage of protein extracted, and pH of brain were not different between groups. No changes in total synapsin or synaptophysin in the hippocampus were produced by injecting rats with either lithium or haloperidol for 30 days. Reductions in synapsin in both patients with schizophrenia (synapsin IIa and IIIa) and bipolar disorder (synapsin Ia, IIa and IIIa) imply that altered or reduced synaptic function in the hippocampus may be involved in these disorders.
多项研究表明,突触前蛋白表达降低可能是精神分裂症的特征。我们在精神分裂症和双相情感障碍中研究了一种这样的蛋白,即突触素。使用了来自对照组(n = 13)、精神分裂症患者(n = 16)、双相情感障碍患者(n = 6)以及自杀受害者(n = 7)的海马组织样本。通过蛋白质免疫印迹法,使用检测突触素Ia、IIa和IIIa蛋白的抗体,对膜和胞质部分的突触素进行分析。还测量了突触囊泡蛋白以便进行比较。与对照组相比,精神分裂症患者(P = 0.034)和双相情感障碍患者(P = 0.00008)的总突触素显著降低。精神分裂症和双相情感障碍患者以及自杀受害者的突触素/突触囊泡蛋白比率均降低(P = 0.014)。各组之间的年龄、死后间隔时间、提取的蛋白质百分比以及脑的pH值并无差异。给大鼠注射锂盐或氟哌啶醇30天,未引起海马中总突触素或突触囊泡蛋白的变化。精神分裂症患者(突触素IIa和IIIa)和双相情感障碍患者(突触素Ia、IIa和IIIa)中突触素的减少意味着海马中突触功能的改变或降低可能与这些疾病有关。