Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Cells. 2020 Jan 28;9(2):313. doi: 10.3390/cells9020313.
Genetic disruption of synaptic proteins results in a whole variety of human neuropsychiatric disorders including intellectual disability, schizophrenia or autism spectrum disorder (ASD). In a wide range of these so-called synaptopathies a sex bias in prevalence and clinical course has been reported. Using an unbiased proteomic approach, we analyzed the proteome at the interaction site of the pre- and postsynaptic compartment, in the prefrontal cortex, hippocampus, striatum and cerebellum of male and female adult C57BL/6J mice. We were able to reveal a specific repertoire of synaptic proteins in different brain areas as it has been implied before. Additionally, we found a region-specific set of novel synaptic proteins differentially expressed between male and female individuals including the strong ASD candidates DDX3X, KMT2C, MYH10 and SET. Being the first comprehensive analysis of brain region-specific synaptic proteomes from male and female mice, our study provides crucial information on sex-specific differences in the molecular anatomy of the synapse. Our efforts should serve as a neurobiological framework to better understand the influence of sex on synapse biology in both health and disease.
突触蛋白的遗传破坏导致了多种人类神经精神疾病，包括智力障碍、精神分裂症或自闭症谱系障碍（ASD）。在广泛的所谓突触病中，已经报道了患病率和临床过程中的性别偏见。我们使用一种无偏的蛋白质组学方法，分析了成年雄性和雌性 C57BL/6J 小鼠前额叶皮层、海马体、纹状体和小脑突触前和突触后隔室相互作用部位的蛋白质组。正如之前所暗示的那样，我们能够揭示不同脑区特定的突触蛋白谱。此外，我们发现了一组特定于区域的新型突触蛋白，它们在雄性和雌性个体之间表达不同，包括强烈的 ASD 候选基因 DDX3X、KMT2C、MYH10 和 SET。作为对雄性和雌性小鼠特定脑区突触蛋白质组的首次全面分析，我们的研究提供了关于突触分子解剖结构中性别特异性差异的关键信息。我们的努力应该为更好地理解性别对健康和疾病中突触生物学的影响提供神经生物学框架。
