Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
PLoS One. 2013 Apr 22;8(4):e59458. doi: 10.1371/journal.pone.0059458. Print 2013.
Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia.
听觉处理缺陷是精神分裂症中记录最完善的内表型之一，这可能是由于兴奋性突触连接丧失所致。精神分裂症患者的树突棘减少，树突棘是兴奋性投射的主要突触后靶标。p21 激活激酶 1（PAK1）调节肌动蛋白细胞骨架和树突棘密度，是 kalirin 和 CDC42 的下游效应物，两者在精神分裂症中表达改变。本研究通过对 25 名精神分裂症患者和匹配对照的定量 Western blot 检测，旨在确定精神分裂症患者是否存在听觉皮层 PAK1 蛋白表达减少。在我们的队列中，未发现精神分裂症患者的 PAK1 水平有显著变化。同一对受试者内的 PAK1 蛋白水平与同一对受试者中总 kalirin 蛋白的先前测量值呈正相关。PAK1 水平还与树突棘标志物 spinophilin 的水平相关。后两项发现表明，我们的测定法不能检测到 PAK1 蛋白表达的有意义差异，因此 PAK1 水平在精神分裂症中没有变化并非由于其检测灵敏度有限。需要进一步研究以评估 PAK1 磷酸化状态的改变或 PAK 家族其他成员的蛋白表达改变是否存在于精神分裂症中。
