IRCCS Centro Neurolesi Bonino Pulejo, Strada Statale 113, C.da Casazza, 98124, Messina, Italy.
Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
Neuroscience. 2019 May 15;406:333-344. doi: 10.1016/j.neuroscience.2019.03.008. Epub 2019 Mar 12.
Exploring sexual dimorphisms in the brain morphology is important for their impact and therapeutic implications for several neurological diseases. The hypothesis that sex could influence the transcriptome of brain cells could be the basis regarding the different response to cognitive decline identified in men and women. In this paper, we analyzed several prefrontal cortices (PFC) microarrays datasets of young/middle-aged healthy subjects and then Alzheimer's disease (AD) patients, according to the sex. The significant transcriptomes were overlapped with the main genes characterizing cells of the central nervous system (CNS) in order to determine the respective weighted percentages of significantly expression gene modulation (WPSEG). We identified differences in brain transcriptional activity between young and middle-aged. In middle-aged women, the WPSEG were higher for the Astrocytes, the Endotheliocytes, and the Microglia. In addition, the sex-matched analysis of transcriptome identified a convergent molecular signature in men and women AD patients. Furthermore, the WPSEG belonging to CNS cells in PFC of healthy middle-aged subjects was correlated to AD profiles according to the sex. Since our results, it is possible to conclude that during the aging the PFC' cells adopt transcriptional strategies sex-dependent that could potentially control the development of neurodegenerative diseases.
探索大脑形态的性别二态性对于理解其对多种神经退行性疾病的影响和治疗意义非常重要。性别可能影响脑细胞转录组的假设可能是导致男性和女性认知能力下降反应不同的基础。在本文中，我们根据性别分析了几个年轻/中年健康受试者和阿尔茨海默病（AD）患者的前额叶皮质（PFC）微阵列数据集。将显著的转录组与中枢神经系统（CNS）主要特征细胞的主要基因重叠，以确定显著表达基因调节的各自加权百分比（WPSEG）。我们发现了年轻人和中年人之间大脑转录活性的差异。在中年女性中，星形胶质细胞、内皮细胞和小胶质细胞的 WPSEG 更高。此外，对 AD 患者的性别匹配转录组分析确定了男女患者中存在趋同的分子特征。此外，健康中年受试者 PFC 中属于 CNS 细胞的 WPSEG 根据性别与 AD 谱相关。鉴于我们的研究结果，可以得出结论，在衰老过程中，PFC 细胞采用依赖于性别的转录策略，这可能潜在地控制神经退行性疾病的发展。
