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

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

Publication date: Mar 29, 2021

The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions. Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes. WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity. In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.

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Concepts Keywords
Branches of biology
Glial cells
Multiple sclerosis
Neurology
Macrophages
Microglia
Neuroinflammation
Myelin
Demyelinating disease

Semantics

Type Source Name
disease MESH pathology
disease MESH multiple sclerosis
disease MESH Inflammation
disease MESH demyelination
pathway REACTOME Reproduction
disease MESH sclerosis
drug DRUGBANK Trestolone
disease MESH syndrome
disease MESH encephalomyelitis
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Aspartame
drug DRUGBANK Streptomycin
drug DRUGBANK L-Glutamine
drug DRUGBANK Trypsin
disease MESH dissociation
drug DRUGBANK Aminosalicylic Acid
drug DRUGBANK Phenol
drug DRUGBANK L-Lysine
drug DRUGBANK Phosphate ion

Original Article

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