Batzdorf Clara Sophie, Morr Anna Sophie, Bertalan Gergely, Sack Ingolf, Silva Rafaela Vieira, Infante-Duarte Carmen
Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Lindenberger Weg 80, 13125 Berlin, Germany.
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Biology (Basel). 2022 Jan 31;11(2):230. doi: 10.3390/biology11020230.
Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In an animal model of MS, named experimental autoimmune encephalomyelitis (EAE), we have previously shown that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, here we aimed at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, the gene expression of the key basement membrane components laminin (), collagen (), and fibronectin () were investigated by RT-qPCR. We showed that the healthy male cortex expressed less , , and , but more (all < 0.05) than the healthy female cortex, which was associated with 9% softer properties ( = 0.044) in that region. At peak EAE cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females ( = 0.006). Cortical , and expression increased 2 to 3-fold in EAE in both sexes while decreased only in males (all < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.
磁共振弹性成像（MRE）已揭示健康个体和多发性硬化症（MS）患者大脑硬度存在性别差异。在一种名为实验性自身免疫性脑脊髓炎（EAE）的MS动物模型中，我们之前已经表明炎症诱导的脑软化与细胞外基质（ECM）的改变有关。然而，尚不清楚脑ECM是否具有可通过MRE可视化的性别特异性特性。因此，在这里我们旨在量化健康和发炎大脑中与ECM变化相关的脑粘弹性的性别差异。将多频MRE应用于雌雄健康和EAE小鼠的中脑，以定量绘制区域硬度图。为了确定脑ECM组成的差异，通过RT-qPCR研究了关键基底膜成分层粘连蛋白（）、胶原蛋白（）和纤连蛋白（）的基因表达。我们发现，健康雄性皮质表达的、和较少，但比健康雌性皮质表达的更多（均<0.05），这与该区域软9%的特性相关（=0.044）。与健康组织相比，在EAE高峰期，两性皮质软化程度相似，雄性和雌性之间仍存在8%的差异（=0.006）。在EAE中，两性皮质、和的表达均增加了2至3倍，而仅在雄性中减少（均<0.05）。在其他脑区未检测到明显的硬度性别差异。总之，小鼠大脑皮质组织ECM组成的性别差异通过MRE测量的体内硬度得以体现，未来研究应考虑按性别设定参考值。
