Effects of the extracellular matrix on myelin development and regeneration in the central nervous system

Shu, Min; Soomro, Shahid Hussain; Jie, Jifu; Fu, Hui

doi:10.1016/j.tice.2020.101444

Cited by 17 publications

(22 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Various extracellular matrix (ECM) molecules including chondroitin sulfate proteoglycans (CSPGs) contribute to the inhibitory microenvironment of MS lesions 8 – 10 . An important subgroup of CSPGs is the lecticans that include 4 members: brevican, neurocan, aggrecan and versican.…”

Section: Introductionmentioning

confidence: 99%

Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination

et al. 2022

View full text Add to dashboard Cite

Remyelination failure in multiple sclerosis (MS) contributes to progression of disability. The deficient repair results from neuroinflammation and deposition of inhibitors including chondroitin sulfate proteoglycans (CSPGs). Which CSPG member is repair-inhibitory or alters local inflammation to exacerbate injury is unknown. Here, we correlate high versican-V1 expression in MS lesions with deficient premyelinating oligodendrocytes, and highlight its selective upregulation amongst CSPG members in experimental autoimmune encephalomyelitis (EAE) lesions modeling MS. In culture, purified versican-V1 inhibits oligodendrocyte precursor cells (OPCs) and promotes T helper 17 (Th17) polarization. Versican-V1-exposed Th17 cells are particularly toxic to OPCs. In NG2CreER:MAPTmGFP mice illuminating newly formed GFP+ oligodendrocytes/myelin, difluorosamine (peracetylated,4,4-difluoro-N-acetylglucosamine) treatment from peak EAE reduces lesional versican-V1 and Th17 frequency, while enhancing GFP+ profiles. We suggest that lesion-elevated versican-V1 directly impedes OPCs while it indirectly inhibits remyelination through elevating local Th17 cytotoxic neuroinflammation. We propose CSPG-lowering drugs as potential dual pronged repair and immunomodulatory therapeutics for MS.

show abstract

Section: Introductionmentioning

confidence: 99%

Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination

et al. 2022

View full text Add to dashboard Cite

show abstract

“…According to previous research, the overlapped six KEGG pathways in the overlapped DEGs datasets between the IVF-ET and IVF-FET groups were associated with the functions of nervous system. For instance, the ECM-receptor interaction pathway plays a pivotal role in the pathogenesis of several neurodegenerative and neuroinflammatory disorders, as the direct or indirect control of cellular processes such as adhesion, migration, differentiation, proliferation, and apoptosis ( Kerrisk et al 2014 , Mardpour et al 2019 , Sun et al 2020 , Virtuoso et al 2020 , Su et al 2021 ). Focal adhesion, phagosome, CAMs, and cellular senescence are enriched KEGG terms.…”

Section: Discussionmentioning

confidence: 99%

“…Focal adhesion, phagosome, CAMs, and cellular senescence are enriched KEGG terms. These KEGG pathways interact with each other and participate in the ECM-receptor interaction pathway ( Kerrisk et al 2014 , Mardpour et al 2019 , Sun et al 2020 , Virtuoso et al 2020 , Su et al 2021 ). Furthermore, PI3K/AKT signalling pathway is strongly associated with anxiety and depression behaviours through hippocampal plasticity, cell growth, proliferation, survival, and metabolism ( Gimenez-Llort et al 2020 , Neis et al 2020 , Palumbo et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception

et al. 2021

View full text Add to dashboard Cite

The number of children born after assisted reproductive technology (ART) are accumulating rapidly and the healthy problems of the children are extensively concerned. This study aims to evaluate whether the ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET) and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Aged (18 months old), but not young (3 months old) male offspring, in the IVF-ET and IVF-FET groups, compared with these in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA Sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in future.

show abstract

“…Significant progress has been made in vitro and in animal models in identifying molecules and mechanisms that promote or inhibit remyelination (Franklin, 2002 ; Franklin and Ffrench-Constant, 2017 ). Amongst the latter, extracellular matrix (ECM) components are dynamically remodeled during injury and their interactions with surrounding cells exposing new epitopes or receptors induce injury-related pathological pathways (Zimmermann and Dours-Zimmermann, 2008 ; de Jong et al, 2020 ; Srivastava et al, 2020 ; Su et al, 2021 ). Upregulation of ECM components, including chondroitin sulfate proteoglycans (CSPGs), tenascins, and fragmented hyaluronan, block steps in OPC differentiation and myelination and are implicated in contributing to remyelination failure (Czopka et al, 2010 ; Karus et al, 2016 ; Srivastava et al, 2020 ; Su et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

CAQK, a peptide associating with extracellular matrix components targets sites of demyelinating injuries

Abi‐Ghanem

Jonnalagadda

Chun

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The destruction of the myelin sheath that encircles axons leads to impairments of nerve conduction and neuronal dysfunctions. A major demyelinating disorder is multiple sclerosis (MS), a progressively disabling disease in which immune cells attack the myelin. To date, there are no therapies to target selectively myelin lesions, repair the myelin or stop MS progression. Small peptides recognizing epitopes selectively exposed at sites of injury show promise for targeting therapeutics in various pathologies. Here we show the selective homing of the four amino acid peptide, cysteine-alanine-lysine glutamine (CAQK), to sites of demyelinating injuries in three different mouse models. Homing was assessed by administering fluorescein amine (FAM)-labeled peptides into the bloodstream of mice and analyzing sites of demyelination in comparison with healthy brain or spinal cord tissue. FAM-CAQK selectively targeted demyelinating areas in all three models and was absent from healthy tissue. At lesion sites, the peptide was primarily associated with the fibrous extracellular matrix (ECM) deposited in interstitial spaces proximal to reactive astrocytes. Association of FAM-CAQK was detected with tenascin-C although tenascin depositions made up only a minor portion of the examined lesion sites. In mice on a 6-week cuprizone diet, FAM-CAQK peptide crossed the nearly intact blood-brain barrier and homed to demyelinating fiber tracts. These results demonstrate the selective targeting of CAQK to demyelinating injuries under multiple conditions and confirm the previously reported association with the ECM. This work sets the stage for further developing CAQK peptide targeting for diagnostic and therapeutic applications aimed at localized myelin repair.

show abstract

Effects of the extracellular matrix on myelin development and regeneration in the central nervous system

Cited by 17 publications

References 96 publications

Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination

Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception

CAQK, a peptide associating with extracellular matrix components targets sites of demyelinating injuries

Contact Info

Product

Resources

About