Sexual Dimorphism in Extracellular Matrix Composition and Viscoelasticity of the Healthy and Inflamed Mouse Brain

• Published in: Biology (Basel, Switzerland) Switzerland), 2022-01, Vol.11 (2), p.230
• Main Authors: Batzdorf, Clara Sophie, Morr, Anna Sophie, Bertalan, Gergely, Sack, Ingolf, Silva, Rafaela Vieira, Infante-Duarte, Carmen
• Format: Article
• Language: English
• Subjects: Animal models; Autoimmune diseases; Brain; brain viscoelasticity; Central nervous system; Collagen; Collagen (type I); Cortex; Experimental allergic encephalomyelitis; experimental autoimmune encephalomyelitis; Extracellular matrix; Fibronectin; Gender; Gene expression; Inflammation; Laboratory animals; Laminin; magnetic resonance elastography; Males; Mechanical properties; Mesencephalon; Multiple sclerosis; Paresis; Sex differences; Sexual dimorphism; Viscoelasticity
• ISSN: 2079-7737; 2079-7737
• 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.