Related Experiment Video
Updated: Jun 16, 2026
09:41
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Pathological extracellular matrix changes in decellularized normal appearing gray matter and subpial multiple
Jody M de Jong1,2, Justina C Wolters3, Marion H C Wijering1,2
1Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Iscience
|June 15, 2026
Summary
Alterations in the extracellular matrix (ECM) within normal-appearing gray matter (NAGM) in multiple sclerosis (MS) impact microglia behavior, potentially driving neurodegeneration and disease progression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease.
- Gray matter lesions (GMLs) and normal-appearing gray matter (NAGM) in MS exhibit neuropathology and are linked to neurodegeneration and disability.
- The extracellular matrix (ECM), including perineuronal nets (PNNs), is crucial for neuronal health and synaptic stability, and its remodeling by microglia influences both cell types.
Purpose of the Study:
- To investigate the composition of the ECM in decellularized human gray matter from control subjects, MS NAGM, and MS GMLs.
- To determine the effects of altered ECM composition on microglial behavior and phenotype.
Main Methods:
- Decellularization of human gray matter tissue (control, NAGM, GML).
- Label-free quantitative mass spectrometry to analyze ECM composition.
- In vitro studies exposing microglia to decellularized ECM slices.
Main Results:
- Differential abundances of PNN ECM components and synaptic/basement membrane ECM components were found in decellularized NAGM compared to controls.
- ECM composition in GMLs was similar to perilesional gray matter.
- Microglia exposed to decellularized NAGM and GML ECM showed reduced IBA1 expression and acquisition of the proinflammatory marker iNOS in some cells.
Conclusions:
- ECM alterations are present in NAGM in MS.
- These ECM changes influence microglial characteristics, potentially contributing to the neuropathology and neurodegeneration observed in MS.
- Targeting ECM-microglia interactions may offer therapeutic strategies for MS.
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