Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin

Wageningen, Thecla A. van; Antonovaité, Nelda; Paardekam, Erik; Brevé, John; Iannuzzi, Davide; Dam, Anne Marie Van

doi:10.1186/s12974-021-02134-x

Cited by 10 publications

(8 citation statements)

References 56 publications

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“…For example, the NF-κB pathway was found to be engaged at a higher level in white matter microglia compared to their grey matter counterparts, possibly providing an explanation as to why microglial inflammation is increased in the former [109]. Additionally, white matter microglia have higher elasticity and viscosity, compared to grey matter microglia [143], which might impact microglial ability to phagocytose [3]. A subset of macrophages has also been identified lining the apical surface of the choroid plexus epithelium, also known as Kolmer's epiplexus cells.…”

Section: Regional and Morphological Differences Of Microgliamentioning

confidence: 99%

White matter microglia heterogeneity in the CNS

et al. 2021

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Microglia, the resident myeloid cells in the central nervous system (CNS) play critical roles in shaping the brain during development, responding to invading pathogens, and clearing tissue debris or aberrant protein aggregations during ageing and neurodegeneration. The original concept that like macrophages, microglia are either damaging (pro-inflammatory) or regenerative (anti-inflammatory) has been updated to a kaleidoscope view of microglia phenotypes reflecting their wideranging roles in maintaining homeostasis in the CNS and, their contribution to CNS diseases, as well as aiding repair. The use of new technologies including single cell/nucleus RNA sequencing has led to the identification of many novel microglia states, allowing for a better understanding of their complexity and distinguishing regional variations in the CNS. This has also revealed differences between species and diseases, and between microglia and other myeloid cells in the CNS. However, most of the data on microglia heterogeneity have been generated on cells isolated from the cortex or whole brain, whereas white matter changes and differences between white and grey matter have been relatively understudied. Considering the importance of microglia in regulating white matter health, we provide a brief update on the current knowledge of microglia heterogeneity in the white matter, how microglia are important for the development of the CNS, and how microglial ageing affects CNS white matter homeostasis. We discuss how microglia are intricately linked to the classical white matter diseases such as multiple sclerosis and genetic white matter diseases, and their putative roles in neurodegenerative diseases in which white matter is also affected. Understanding the wide variety of microglial functions in the white matter may provide the basis for microglial targeted therapies for CNS diseases.

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Section: Regional and Morphological Differences Of Microgliamentioning

confidence: 99%

White matter microglia heterogeneity in the CNS

et al. 2021

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“…Sex-dependent changes in the expression levels of basement membrane proteins seem to have the same net effect on macroscopic viscoelastic properties of the cortex because we observed a similar amount of softening in both sexes. Since tissue stiffness depends on both the cellular and ECM composition, as well as their structural arrangement [ 19 , 22 , 41 , 55 , 68 , 79 ], the combination of up- and downregulation of different matrix components may counterbalance their effect on mechanical properties and may even serve as a protective measure. Future studies with larger group sizes will allow for in-depth analyses of the individual contribution of matrix components to the viscoelastic behavior of the brain.…”

Section: Discussionmentioning

confidence: 99%

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

Batzdorf

Morr

Bertalan

et al. 2022

Biology

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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 (Lama4, Lama5), collagen (Col4a1, Col1a1), and fibronectin (Fn1) were investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, and Col4a1, but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 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 (p = 0.006). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 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.

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“…Very recently, the stiffness of microglial cells was reported to be even softer with an elastic modulus ranging from 40 to 100 Pa ( Rheinlaender et al, 2020 ). Interestingly, microglia derived from gray matter are intrinsically softer (842 Pa) than microglia derived from white matter (1,429 Pa), suggesting that their mechanical properties depend on their spatial location ( van Wageningen et al, 2021 ). This characteristic was also recently confirmed for astrocytes.…”

Section: Mechanobiology Of Brain Cellsmentioning

confidence: 99%

Multiscale Mechanobiology in Brain Physiology and Diseases

Procès

Luciano

Kalukula

et al. 2022

Front. Cell Dev. Biol.

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Increasing evidence suggests that mechanics play a critical role in regulating brain function at different scales. Downstream integration of mechanical inputs into biochemical signals and genomic pathways causes observable and measurable effects on brain cell fate and can also lead to important pathological consequences. Despite recent advances, the mechanical forces that influence neuronal processes remain largely unexplored, and how endogenous mechanical forces are detected and transduced by brain cells into biochemical and genetic programs have received less attention. In this review, we described the composition of brain tissues and their pronounced microstructural heterogeneity. We discuss the individual role of neuronal and glial cell mechanics in brain homeostasis and diseases. We highlight how changes in the composition and mechanical properties of the extracellular matrix can modulate brain cell functions and describe key mechanisms of the mechanosensing process. We then consider the contribution of mechanobiology in the emergence of brain diseases by providing a critical review on traumatic brain injury, neurodegenerative diseases, and neuroblastoma. We show that a better understanding of the mechanobiology of brain tissues will require to manipulate the physico-chemical parameters of the cell microenvironment, and to develop three-dimensional models that can recapitulate the complexity and spatial diversity of brain tissues in a reproducible and predictable manner. Collectively, these emerging insights shed new light on the importance of mechanobiology and its implication in brain and nerve diseases.

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Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin

Cited by 10 publications

References 56 publications

White matter microglia heterogeneity in the CNS

White matter microglia heterogeneity in the CNS

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

Multiscale Mechanobiology in Brain Physiology and Diseases

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