Laboratory of Translational Neuroscience, CEINGE Biotecnologie Avanzate, 80145 Naples, Italy.
Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy.
Int J Mol Sci. 2022 Jan 28;23(3):1539. doi: 10.3390/ijms23031539.
Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin-binding protein cyclase-associated protein 2 (), the sheddase a disintegrin and metalloproteinase 10 (), and the synapse-associated protein 97 (). Our analysis of the SCZ post-mortem brain indicated increased mRNA in DLPFC and decreased mRNA in the hippocampus of SCZ patients, compared to non-psychiatric control subjects, while the transcript was unaffected. Conversely, no differences in , , and protein levels were detected between SCZ and control individuals in both brain regions. To assess whether and transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson's and Alzheimer's disease. Interestingly, also in Parkinson's disease patients, we found a selective reduction of mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies.
精神分裂症 (SCZ) 是一种以异常突触可塑性和连接为特征的精神疾病。大量证据表明,突触后异常与 SCZ 之间存在遗传和功能联系。在这里,我们对 SCZ 患者的背外侧前额叶皮层 (DLPFC) 和海马体进行了定量 PCR 和 Western blot 分析,以研究三种关键的棘突形成蛋白的 mRNA 和蛋白表达:肌动蛋白结合蛋白环化酶相关蛋白 2 ()、解整合素和金属蛋白酶 10 () 和突触相关蛋白 97 ()。我们对 SCZ 尸检大脑的分析表明,与非精神病对照相比,SCZ 患者的 DLPFC 中 mRNA 增加,而海马体中的 mRNA 减少,而 转录本不受影响。相反,在两个脑区,SCZ 患者和对照组之间的 、 和 蛋白水平没有差异。为了评估 和 转录本的改变是否是 SCZ 特有的,我们还测量了它们在受神经退行性疾病(如帕金森病和阿尔茨海默病)影响的额上回中的表达。有趣的是,在帕金森病患者中,我们还发现与对照组相比, mRNA 水平选择性降低,但蛋白水平不变。总之,我们首次报道了精神和神经障碍患者大脑中 表达的改变,这表明该基因的异常表达可能导致这些神经病理学中的突触功能障碍。