Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors

Jong, Jody M. de; Broekaart, Diede W. M.; Bongaarts, Anika; Mühlebner, Angelika; Vliet, Erwin A. van; Aronica, Eleonora

doi:10.3390/biomedicines10102475

Cited by 3 publications

(3 citation statements)

References 252 publications

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“…The first specialized form is perineuronal nets (PNNs), which mostly envelop the inhibitory parvalbumin (PV) expressing interneurons. While the composition of PNNs may vary across different brain regions and change with age, their backbone is composed of chondroitin sulfate proteoglycans (CSPG) lecticans, such as aggrecan, brevican, and neurocan, whose amino terminal regions bind to hyaluronan while their carboxy terminal regions bind to tenascin [ 4 , 5 ]. The second CNS-specific form of the ECM is the basement membrane (BM), including the meningeal BM, which surrounds the pial surfaces, and the vascular BM, which surrounds blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrix Regulation in Physiology and in Brain Disease

Soles

Selimovic

Sbrocco

et al. 2023

IJMS

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The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss the physiological roles of the ECM and its contribution to the pathogenesis of brain disease, highlighting the gene expression changes, transcriptional factors involved, and a role for microglia in ECM regulation. Much of the research conducted thus far on disease states has focused on “omic” approaches that reveal differences in gene expression related to the ECM. Here, we review recent findings on alterations in the expression of ECM-associated genes in seizure, neuropathic pain, cerebellar ataxia, and age-related neurodegenerative disorders. Next, we discuss evidence implicating the transcription factor hypoxia-inducible factor 1 (HIF-1) in regulating the expression of ECM genes. HIF-1 is induced in response to hypoxia, and also targets genes involved in ECM remodeling, suggesting that hypoxia could contribute to ECM remodeling in disease conditions. We conclude by discussing the role microglia play in the regulation of the perineuronal nets (PNNs), a specialized form of ECM in the central nervous system. We show evidence that microglia can modulate PNNs in healthy and diseased brain states. Altogether, these findings suggest that ECM regulation is altered in brain disease, and highlight the role of HIF-1 and microglia in ECM remodeling.

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Section: Introductionmentioning

confidence: 99%

Extracellular Matrix Regulation in Physiology and in Brain Disease

Soles

Selimovic

Sbrocco

et al. 2023

IJMS

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“…It has been experimentally shown that the extracellular matrix of the brain "may contain memory traces of local neural network activity" [28] and participates in the modulation of various types of memory [34], as well as potentially contributing to the formation of epileptogenesis [35][36][37]. Burst activity is known to underlie both information processing [38] and storage [39][40][41], including in memory traces [42], as well as in neuropathologies such as epilepsy [43].…”

Section: Introductionmentioning

confidence: 99%

Bursting Dynamics of Spiking Neural Network Induced by Active Extracellular Medium

Stasenko

Kazantsev

2023

Mathematics

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We propose a mathematical model of a spiking neural network (SNN) that interacts with an active extracellular field formed by the brain extracellular matrix (ECM). The SNN exhibits irregular spiking dynamics induced by a constant noise drive. Following neurobiological facts, neuronal firing leads to the production of the ECM that occupies the extracellular space. In turn, active components of the ECM can modulate neuronal signaling and synaptic transmission, for example, through the effect of so-called synaptic scaling. By simulating the model, we discovered that the ECM-mediated regulation of neuronal activity promotes spike grouping into quasi-synchronous population discharges called population bursts. We investigated how model parameters, particularly the strengths of ECM influence on synaptic transmission, may facilitate SNN bursting and increase the degree of neuronal population synchrony.

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“…There is a prominent activation of both the innate and adaptive immune systems in glioneuronal tumors [30,31]. Altered extracellular matrix (ECM) is another risk factor for epileptogenicity [32 ▪ ]. In this regard, GGs have a higher expression of ECM-related genes, and the expression of laminins, collagens, thrombospondins, and various integrins is higher in GGs than in control tissue [33].…”

Section: Introductionmentioning

confidence: 99%

Epilepsy in gliomas: recent insights into risk factors and molecular pathways

Rudà,

Bruno,

Pellerino

2023

Current Opinion in Neurology

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Purpose of review The purpose of this review is to discuss the molecular pathways governing the development of seizures in glioma patients. Recent findings The intrinsic epileptogenicity of the neuronal component of glioneuronal and neuronal tumors is the most relevant factor for seizure development. The two major molecular alterations behind epileptogenicity are the rat sarcoma virus (RAS)/mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol-3-kinase / protein kinase B / mammalian target of rapamycin (P13K/AKT/mTOR) pathways. The BRAFv600E mutation has been shown in experimental models to contribute to epileptogenicity, and its inhibition is effective in controlling both seizures and tumor growth. Regarding circumscribed astrocytic gliomas, either BRAFv600E mutation or mTOR hyperactivation represent targets of treatment. The mechanisms of epileptogenicity of diffuse lower-grade gliomas are different: in addition to enhanced glutamatergic mechanisms, the isocitrate dehydrogenase (IDH) 1/2 mutations and their product D2-hydroxyglutarate (D2HG), which is structurally similar to glutamate, exerts excitatory effects on neurons also dependent on the presence of astrocytes. In preclinical models IDH1/2 inhibitors seem to impact both tumor growth and seizures. Conversely, the molecular factors behind the epileptogenicity of glioblastoma are unknown. Summary This review summarizes the current state of molecular knowledge on epileptogenicity in gliomas and highlights the relationships between epileptogenicity and tumor growth.

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Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors

Cited by 3 publications

References 252 publications

Extracellular Matrix Regulation in Physiology and in Brain Disease

Extracellular Matrix Regulation in Physiology and in Brain Disease

Bursting Dynamics of Spiking Neural Network Induced by Active Extracellular Medium

Epilepsy in gliomas: recent insights into risk factors and molecular pathways

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