Föcking M, Dicker P, Lopez L M, Hryniewiecka M, Wynne K, English J A, Cagney G, Cotter D R
Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Departments of Epidemiology and Public Health, Royal College of Surgeons in Ireland, Dublin, Ireland.
Transl Psychiatry. 2016 Nov 29;6(11):e959. doi: 10.1038/tp.2016.224.
The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed. Validation of expression changes of DNM1, DTNA, NDUFV2, SEPT11 and SSBP was performed by western blotting. Bioinformatics analysis of the differentially expressed proteins implicated metabolic pathways including mitochondrial function, the tricarboxylic acid cycle, oxidative phosphorylation, protein translation and calcium signaling. The data implicate PSD-associated proteins, and specifically mitochondrial function in bipolar disorder. They relate synaptic function in bipolar disorder and the energy pathways that underpin it. Overall, our findings add to a growing literature linking the PSD and mitochondrial function in psychiatric disorders generally, and suggest that mitochondrial function associated with the PSD is particularly important in bipolar disorder.
突触后致密区（PSD）包含一组复杂的蛋白质，这些蛋白质与精神分裂症和双相情感障碍等神经精神疾病具有已知的相关性。我们从斯坦利医学研究所选取了16个双相情感障碍样本和20个对照样本的前扣带回皮质，对这一解剖结构进行了富集。采用结合无标记定量的非偏倚鸟枪法蛋白质组学来鉴定差异表达的蛋白质。对PSD的定量研究鉴定出2033种蛋白质，其中发现288种存在差异表达。通过蛋白质免疫印迹法对DNM1、DTNA、NDUFV2、SEPT11和SSBP的表达变化进行了验证。对差异表达蛋白质的生物信息学分析涉及包括线粒体功能、三羧酸循环、氧化磷酸化、蛋白质翻译和钙信号传导在内的代谢途径。这些数据表明双相情感障碍与PSD相关蛋白有关，特别是线粒体功能。它们揭示了双相情感障碍中的突触功能以及支撑该功能的能量途径。总体而言，我们的研究结果进一步丰富了将PSD与一般精神疾病中线粒体功能联系起来的文献，并表明与PSD相关的线粒体功能在双相情感障碍中尤为重要。
