Smalla K-H, Mikhaylova M, Sahin J, Bernstein H-G, Bogerts B, Schmitt A, van der Schors R, Smit A B, Li K W, Gundelfinger E D, Kreutz M R
Special Lab Molecular Biological Techniques, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Mol Psychiatry. 2008 Sep;13(9):878-96. doi: 10.1038/mp.2008.60. Epub 2008 May 27.
Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a hypofunction of N-methyl-D-aspartate receptor-mediated signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse. We have employed two-dimensional gel electrophoresis in conjunction with mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine. We found consistent changes in the synaptic proteomes of human schizophrenics and in rats with induced ketamine psychosis compared to controls. However, commonly regulated proteins between both groups were very limited and only prohibitin was found upregulated in both chronic schizophrenia and the rat ketamine model. Prohibitin, however, could be a new potential marker for the synaptic pathology of schizophrenia and might be causally involved in the disease process.
近年来的许多研究表明，精神分裂症是一种突触疾病，关键涉及N-甲基-D-天冬氨酸受体介导的信号传导功能减退。然而，目前尚不清楚这些病理过程如何在突触的蛋白质含量中体现。我们采用二维凝胶电泳结合质谱法来表征和比较慢性精神分裂症患者人类左背外侧前额叶皮质以及用氯胺酮亚慢性处理的大鼠大脑皮质的突触蛋白质组。我们发现，与对照组相比，人类精神分裂症患者和氯胺酮诱导的精神病大鼠的突触蛋白质组存在一致的变化。然而，两组之间共同调控的蛋白质非常有限，仅发现抑制素在慢性精神分裂症和大鼠氯胺酮模型中均上调。然而，抑制素可能是精神分裂症突触病理学的一个新的潜在标志物，并且可能在疾病过程中起因果作用。
