Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7‐mediated chondroitin sulfate proteoglycan production

Kamermans, Alwin; Planting, Kirsten E.; Jalink, Kees; Horssen, Jack van; Vries, Helga E. de

doi:10.1002/glia.23526

Cited by 35 publications

(30 citation statements)

References 56 publications

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“…TRPM2 expression is increased after interleukin stimulation [101]. Reactive astrocytes express high levels of TRPM7, which seems to be important for gliotic scar formation [107]. Like TRPC3, TRPM1 is upregulated after stimulation of microglia with Aβ [108], whereas TRPM2 is involved in microglia activation [109] after interleukin stimulation [101].…”

Section: Trp Channelsmentioning

confidence: 99%

Strategies for Neuroprotection in Multiple Sclerosis and the Role of Calcium

Enders

Heider

Ludwig

et al. 2020

IJMS

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Calcium ions are vital for maintaining the physiological and biochemical processes inside cells. The central nervous system (CNS) is particularly dependent on calcium homeostasis and its dysregulation has been associated with several neurodegenerative disorders including Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease (HD), as well as with multiple sclerosis (MS). Hence, the modulation of calcium influx into the cells and the targeting of calcium-mediated signaling pathways may present a promising therapeutic approach for these diseases. This review provides an overview on calcium channels in neurons and glial cells. Special emphasis is put on MS, a chronic autoimmune disease of the CNS. While the initial relapsing-remitting stage of MS can be treated effectively with immune modulatory and immunosuppressive drugs, the subsequent progressive stage has remained largely untreatable. Here we summarize several approaches that have been and are currently being tested for their neuroprotective capacities in MS and we discuss which role calcium could play in this regard.

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Section: Trp Channelsmentioning

confidence: 99%

Strategies for Neuroprotection in Multiple Sclerosis and the Role of Calcium

Enders

Heider

Ludwig

et al. 2020

IJMS

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“…MS is an inflammatory auto-immune disease characterized by gradual loss of myelination in the CNS. Several lecticans such as neurocan, aggrecan, and versican are known to be upregulated around MS lesions ( 59 , 60 ). CSPGs in the multiple sclerosis are known to facilitate the activity and migration of leucocytes the central nervous system ( 61 ).…”

Section: Lecticans and Neuroinflammationmentioning

confidence: 99%

Extracellular matrixes and neuroinflammation

et al. 2020

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The extracellular matrix is a critical component of every human tissue. ECM not only functions as a structural component but also regulates a variety of cellular processes such as cell migration, differentiation, proliferation, and cell death. In addition, current studies suggest that ECM is critical for the pathophysiology of various human diseases. ECM is composed of diverse components including several proteins and polysaccharide chains such as chondroitin sulfate, heparan sulfate, and hyaluronic acid. Each component of ECM exerts its own functions in cellular and pathophysiological processes. One of the interesting recent findings is that ECM is involved in inflammatory responses in various human tissues. In this review, we summarized the known functions of ECM in neuroinflammation after acute injury and chronic inflammatory diseases of the central nerve systems.

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“…As in toxin-induced demyelination rodent models, ASTR reactivity differs between GM and WM MS lesions. Hypertrophic ASTRs form a glial scar in and around inflammatory WM lesions, but not around lesions in the GM [ 12 , 15 , 44 , 45 ]. This difference in ASTR reactivity may contribute to the more efficient remyelination in GM MS lesions [ 3 , 37 , 41 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional heterogeneity between primary adult grey and white matter astrocytes underlie differences in modulation of in vitro myelination

Werkman

Dubbelaar

Vlies

et al. 2020

J Neuroinflammation

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Background Multiple sclerosis (MS) is an inflammation-mediated demyelinating disease of the central nervous system that eventually results in secondary axonal degeneration due to remyelination failure. Successful remyelination is orchestrated by astrocytes (ASTRs) and requires sequential activation, recruitment, and maturation of oligodendrocyte progenitor cells (OPCs). In both MS and experimental models, remyelination is more robust in grey matter (GM) than white matter (WM), which is likely related to local differences between GM and WM lesions. Here, we investigated whether adult gmASTRs and wmASTRs per se and in response to MS relevant Toll-like receptor (TLR) activation differently modulate myelination. Methods Differences in modulation of myelination between adult gmASTRs and wmASTRs were examined using an in vitro myelinating system that relies on a feeding layer of ASTRs. Transcriptional profiling and weighted gene co-expression network analysis were used to analyze differentially expressed genes and gene networks. Potential differential modulation of OPC proliferation and maturation by untreated adult gmASTRs and wmASTRs and in response to TLR3 and TLR4 agonists were assessed. Results Our data reveal that adult wmASTRs are less supportive to in vitro myelination than gmASTRs. WmASTRs more abundantly express reactive ASTR genes and genes of a neurotoxic subtype of ASTRs, while gmASTRs have more neuro-reparative transcripts. We identified a gene network module containing cholesterol biosynthesis enzyme genes that positively correlated with gmASTRs, and a network module containing extracellular matrix-related genes that positively correlated with wmASTRs. Adult wmASTRs and gmASTRs responding to TLR3 agonist Poly(I:C) distinctly modulate OPC behavior, while exposure to TLR4 agonist LPS of both gmASTRs and wmASTRs results in a prominent decrease in myelin membrane formation. Conclusions Primary adult gmASTRs and wmASTRs are heterogeneous at the transcriptional level, differed in their support of in vitro myelination, and their pre-existing phenotype determined TLR3 agonist responses. These findings point to a role of ASTR heterogeneity in regional differences in remyelination efficiency between GM and WM lesions.

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Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7‐mediated chondroitin sulfate proteoglycan production

Cited by 35 publications

References 56 publications

Strategies for Neuroprotection in Multiple Sclerosis and the Role of Calcium

Strategies for Neuroprotection in Multiple Sclerosis and the Role of Calcium

Extracellular matrixes and neuroinflammation

Transcriptional heterogeneity between primary adult grey and white matter astrocytes underlie differences in modulation of in vitro myelination

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