Pathophysiology of the brain extracellular matrix: a new target for remyelination

Lau, Lorraine; Cua, Rowena; Keough, Michael B.; Haylock‐Jacobs, Sarah

doi:10.1038/nrn3550

Cited by 467 publications

(454 citation statements)

References 81 publications

(94 reference statements)

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“…[38][39][40] In many scaffold-based cultures, the scaffold introduces foreign ECM to the microenvironment, which can potentially modify cell behavior and mask disease-related changes in the culture model. In the spheroids of this work, the cells produced all of the ECM.…”

Section: Versatile Culturementioning

confidence: 99%

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

Dingle

Boutin

Chirila

et al. 2015

Tissue Engineering Part C: Methods

122

117

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There is a high demand for in vitro models of the central nervous system (CNS) to study neurological disorders, injuries, toxicity, and drug efficacy. Three-dimensional (3D) in vitro models can bridge the gap between traditional two-dimensional culture and animal models because they present an in vivo-like microenvironment in a tailorable experimental platform. Within the expanding variety of sophisticated 3D cultures, scaffold-free, self-assembled spheroid culture avoids the introduction of foreign materials and preserves the native cell populations and extracellular matrix types. In this study, we generated 3D spheroids with primary postnatal rat cortical cells using an accessible, size-controlled, reproducible, and cost-effective method. Neurons and glia formed laminin-containing 3D networks within the spheroids. The neurons were electrically active and formed circuitry through both excitatory and inhibitory synapses. The mechanical properties of the spheroids were in the range of brain tissue. These in vivo-like features of 3D cortical spheroids provide the potential for relevant and translatable investigations of the CNS in vitro.

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Section: Versatile Culturementioning

confidence: 99%

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

Dingle

Boutin

Chirila

et al. 2015

Tissue Engineering Part C: Methods

122

117

View full text Add to dashboard Cite

show abstract

“…ECM molecules are produced by the Golgi apparatus in neurons and glial cells [1][2][3][4]. ECM molecules play an important role during the development and in the adult brain in normal and pathological conditions, including regeneration processes [4][5][6][7][8]. Presently, multiple interactions between ECM molecules and a number of receptors on the cell surface, including those which are linked to cytoskeleton and tyrosine kinase were identified [9,10].…”

Section: Introduction the Brain Extracellular Matrix (Ecm)mentioning

confidence: 99%

“…All these properties of ECM might play a number of important functions for the nervous system and therefore, ECM might be involved in many physiological and pathophysiological conditions [5,7,10,36].…”

Section: Introduction the Brain Extracellular Matrix (Ecm)mentioning

confidence: 99%

“…Depending on the localization in the brain, ECM can be classified in the following categories: 1) basal membrane matrix, located between endothelial (vascular smooth muscle cells) and the parenchymal cells in the CNS (neurons and glia), composed of collagen, laminin-entactin complex, fibronectin, dystroglycan and perlikan; 2) perineuronal nets, represented by dense, well-structured nets surrounding neurons and proximal dendrites, which includes: proteoglycans, tenascin-R proteins and link proteins; 3) interstitial matrix, localized between parenchymal cells of the central nervous system, which is composed of proteoglycans, hyaluronic acid, tenascin-R, link proteins and a small amount of fibronectin and laminin [5,[37][38][39].…”

Section: Introduction the Brain Extracellular Matrix (Ecm)mentioning

confidence: 99%

“…Also ECM molecules participate in structural rearrangements, that take place during synaptic plasticity in the adult brain due to matrix metalloproteinases (MMP) activity [9,[13][14][15][16], and during regeneration of processes [4,17,18]. The expression of ECM components, however, inhibit the functional recovery after spinal cord injury [5,[19][20][21]. The remodeling of ECM had been demonstrated to take place after brain traumas and in the development of neurodegenerative disorders and in epilepsy.…”

Section: Introduction the Brain Extracellular Matrix (Ecm)mentioning

confidence: 99%

See 2 more Smart Citations

The Role of the Brain Extracellular Matrix in Synaptic Plasticity After Brain Injuries (Review)

Dembitskaya¹,

Tyurikova²,

Semyanov³

2016

Sovrem Tehnol Med

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The brain extracellular matrix is secreted by neurons and glial cells and represents a molecular net comprised of polysaccharides and proteins, fulfilling the space between cells in the tissue. A complex structure and ubiquitous localization of extracellular matrix underlie its involvement in numerous important brain functions, such as diffusion regulation, molecular cell-to-cell interactions, synaptic plasticity and learning. Additionally, the brain extracellular matrix participates in regeneration of neuronal connections after brain and spinal cord injuries. The ability to regenerate connections attenuates by the fast proliferation of the brain extracellular matrix, when its degradation leads to regeneration improvement. Therefore, the brain extracellular matrix represents an important direction of clinical research and possible target for therapeutic interventions. Here we not only describe the structure of the brain extracellular matrix and its sites of localization in the brain, but also make an overview of the influence of the brain extracellular matrix in synaptic plasticity, learning and memory. This review describes the role of the brain extracellular matrix for connection recovery after brain and spinal cord injuries. Here, we highlight the positive ability of enzymatic removal of extracellular matrix component -chondroitin sulphate proteoglycans by chondroitinase ABC to promote restoration of neuronal connections. In conclusion, we discuss possible side effects of treatments requiring the enzymatic removal of chondroitin sulphate proteoglycans on synaptic plasticity and speculate about future development of the field of the brain extracellular matrix research.

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Comparative transcriptomics of the garden dormouse hypothalamus during hibernation

Haugg,

Borner,

Stalder

et al. 2023

FEBS Open Bio

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Torpor or heterothermy is an energy saving mechanism used by endotherms to overcome harsh environmental conditions. During winter, the garden dormouse (Eliomys quercinus) hibernates with multiday torpor bouts and body temperatures of a few degrees Celsius, interrupted by brief euthermic phases. This study investigates gene expression within the hypothalamus, the key brain area controlling energy balance, adding information on differential gene expression potentially relevant to orchestrate torpor. A de novo assembled transcriptome of the hypothalamus was generated from garden dormice hibernating under constant darkness without food and water at 5 °C. Samples were collected during early torpor, late torpor, and interbout arousal. During early torpor, 765 genes were differentially expressed as compared with interbout arousal. Twenty‐seven pathways were over‐represented, including pathways related to hemostasis, extracellular matrix organization and signaling of small molecules. Only 82 genes were found to be differentially expressed between early and late torpor, and no pathways were over‐represented. During late torpor, 924 genes were differentially expressed relative to interbout arousal. Despite the high number of differentially expressed genes, only 10 pathways were over‐represented. Of these, eight were also observed to be over‐represented when comparing early torpor and interbout arousal. Our results are largely consistent with previous findings in other heterotherms. The addition of a transcriptome of a novel species may help to identify species‐specific and overarching torpor mechanisms through future species comparisons.

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Pathophysiology of the brain extracellular matrix: a new target for remyelination

Cited by 467 publications

References 81 publications

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

The Role of the Brain Extracellular Matrix in Synaptic Plasticity After Brain Injuries (Review)

Comparative transcriptomics of the garden dormouse hypothalamus during hibernation

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