Translational Medicine, Cranfield Health, Cranfield University, Cranfield, United Kingdom.
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, United Kingdom.
Neurosci Lett. 2021 Feb 6;745:135629. doi: 10.1016/j.neulet.2021.135629. Epub 2021 Jan 10.
There is converging evidence of dendritic spine dysfunction in schizophrenia. In the present study we hypothesized that the expression of key proteins involved in dendritic spine development and stability may be affected in schizophrenia. Postmortem frontal cortex (BA6) from patients with schizophrenia, major depressive disorder, bipolar disorder and healthy controls was processed for glutamate post-synaptic fraction extraction and post-synaptic density purification. Protein expression of the post-synaptic fraction and the post-synaptic density was assessed using immunoprecipitation and Western blotting respectively. The expression of the N-methyl-d-aspartate glutamate receptor (NMDAR) subunit NR2A, post-synaptic density 95 (PSD-95), Ca/calmodulin-dependent protein kinase II subunits α and β (CaMKIIα and β) were significantly reduced in schizophrenia. A significant decrease in the expression of NR2A was also observed in patients with major depressive disorder relative to controls, but not in patients with bipolar disorder. These results add to existing evidence for disturbed post-synaptic glutamate function and synaptic plasticity in schizophrenia. There may also be subtle disturbances in the post-synaptic glutamatergic function in major depressive disorder.
精神分裂症中存在树突棘功能障碍的证据。本研究假设树突棘发育和稳定性相关的关键蛋白表达可能会受到影响。对精神分裂症、重度抑郁症、双相情感障碍和健康对照组患者的额皮质（BA6）进行谷氨酸后突触小体提取和后突触密度纯化处理。使用免疫沉淀和 Western blot 分别评估后突触小体和后突触密度的蛋白表达。N-甲基-D-天冬氨酸谷氨酸受体（NMDAR）亚基 NR2A、后突触密度 95（PSD-95）、钙/钙调蛋白依赖性蛋白激酶 II 亚基α和β（CaMKIIα 和β）在精神分裂症患者中表达明显降低。与对照组相比，重度抑郁症患者的 NR2A 表达也明显下降，但双相情感障碍患者没有。这些结果为谷氨酸能后突触功能和精神分裂症中的突触可塑性紊乱提供了更多的证据。在重度抑郁症中，谷氨酸能后突触功能可能也存在细微紊乱。
