Dean Brian, Boer Simone A, Mackinnon Andrew, Berk Michael
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Parkville, Victoria, Australia.
Schizophr Res. 2007 Jul;93(1-3):51-7. doi: 10.1016/j.schres.2007.02.022. Epub 2007 Mar 30.
mRNA for 14-3-3zeta, an abundant signalling protein in human CNS, is reported as decreased or unchanged in cortex from subjects with schizophrenia. Addressing this dichotomy, using Western blot analyses, we measured levels of 14-3-3zeta proteins in cortex and caudate nucleus from subjects with schizophrenia, bipolar disorder, age/sex matched controls and in analogous CNS regions from rats treated with psychotropic drugs. Anti-14-3-3zeta antibody bound to three proteins (molecular weights: 27, 54 and 70 kDa), in all CNS tissue. Levels of all proteins did not vary with diagnoses (27 kDa: F(2,42.0)=0.35, p=0.71; 54 kDa: F(2,42.1)=0.62, p=0.54; 70 kDa: F(2,41.0)=2.43, p=0.10). By contrast, independent of diagnoses, there were significant increases in the levels of the 27 kDa protein (+32%; p<0.001) and 54 kDa protein (51%; p=0.001) in the caudate nucleus from males compared to females. In addition, there was a trend (-25%; p=0.06) to decreased levels of the 70 kDa protein in BA 9 in males compared to females. Treating with haloperidol, olanzapine, lithium or a combination thereof did not alter 14-3-3zeta levels in rat cortex or striatum. Therefore, this study suggests that 14-3-3zeta proteins are not altered in the cortex or caudate nucleus in schizophrenia, bipolar disorder or in analogous regions in psychotropic drug treated rats. By contrast, our study suggests that levels of 14-3-3zeta in some regions of the human CNS may be modulated by some sex-specific mechanism.
据报道，14-3-3ζ（一种在人类中枢神经系统中含量丰富的信号蛋白）的信使核糖核酸（mRNA）在精神分裂症患者的大脑皮层中减少或未发生变化。为解决这一矛盾，我们采用蛋白质免疫印迹分析方法，检测了精神分裂症患者、双相情感障碍患者、年龄/性别匹配的对照组以及接受精神药物治疗的大鼠相应中枢神经系统区域的大脑皮层和尾状核中14-3-3ζ蛋白的水平。抗14-3-3ζ抗体在所有中枢神经系统组织中均与三种蛋白质（分子量分别为27、54和70 kDa）结合。所有蛋白质的水平在不同诊断组间并无差异（27 kDa：F(2,42.0)=0.35，p=0.71；54 kDa：F(2,42.1)=0.62，p=0.54；70 kDa：F(2,41.0)=2.43，p=0.10）。相比之下，与诊断无关，雄性尾状核中27 kDa蛋白水平显著升高（+32%；p<0.001），54 kDa蛋白水平升高（51%；p=0.001）。此外，与雌性相比，雄性BA9区域中70 kDa蛋白水平有降低趋势（-25%；p=0.06）。用氟哌啶醇、奥氮平、锂盐或它们的组合进行治疗，并未改变大鼠大脑皮层或纹状体中14-3-3ζ的水平。因此，本研究表明，在精神分裂症、双相情感障碍或接受精神药物治疗的大鼠相应区域中，大脑皮层或尾状核中的14-3-3ζ蛋白未发生改变。相比之下，我们的研究表明，人类中枢神经系统某些区域的14-3-3ζ水平可能受某些性别特异性机制的调节。
