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A role for Schwann cell-derived neuregulin-1 in remyelination.

After peripheral nerve injury, axons regenerate and become remyelinated by resident Schwann cells. However, myelin repair never results in t … tant mice lacking a functional Nrg1 gene in Schwann cells are fully myelinated but exhibit impaired remyelination in adult life. We suggest a model in which loss of axonal contact triggers denervated Schwann cells to transiently express NRG1 as an autocrine/paracrine signal that promotes Schwann cell differentiation and remyelination.

Dicer deficiency affects microglial function during demyelination and impairs remyelination.

Microglia are essential regulators of central nervous system (CNS) homeostasis, playing key roles in demyelination and remyelination. Dysregulated microglial activity contributes to pathological inflammation and impaired repair processes in demyelinating diseases. Here, we investigate the role of Dicer1, a critical enzyme in microRNA biogenesis, in affecting microglial function, demyelination, and remyelination. Loss of Dicer1 in microglia resulted in amplified inflammatory responses, defective myelin debris clearance, and disruption of metabolic homeostasis, leading to exacerbated demyelinati…

Treadmill Training-Induced Remyelination Rescues Cognitive Impairment After Acute Hypoxia.

Acute and chronic exposure to high altitude causes multiple negative neurological consequences. Further research has shown the efficacy of t … yelin repair and functional restoration, which should provide new insight for the rehabilitation of remyelination by exercise.

Выздоровление, вызванное недержанием черепицы, не зависит от восстановления.

Дисфункция контроля мочевого пузыря (недержание) является значительной коморбидностью при множественном склерозе, который снижает качество жизни пациентов и является одной из главных причин госпитализации. Последние данные свидетельствуют о том, что демиелинизация CNS достаточна для того, чтобы вызвать недержание, в то время как контроль мочевого пузыря также восстанавливается после ремиелиции. Основываясь на этой сильной связи, мы предположили, что воспоминание необходимо для восстановления контроля функции мочевого пузыря после острого обезвоживания. Чтобы проверить это, мы провели оценку из

Совпадение в аннотации оригинала
Dysfunction in bladder control (incontinence) is a significant comorbidity in multiple sclerosis that diminishes patients' quality of life and is a leading cause of hospitalization. Recent evidence indicates that CNS demyelination is sufficient to induce incontinence, while bladder control is also restored following remyelination. Based on this strong associ…

Усиление ремиэлизации в множестве склероза через M1 Muscarinic ацетилхолиновый рецептор.

Растет распространенность склероза (MS), однако по-прежнему требуется лечение, способное обратить вспять прогресс в развитии болезни. Одна из стратегий, которая продемонстрировала многообещающее изменение режима MS, заключается в воспрещении рецептора M1 — члена семейства мускаринических ацетилхолинов (mAChR). Считается, что антагонизм M1 mAChR является механизмом, с помощью которого Клемастин, развивающийся препарат, который был замечен в целях усиления миелинизации в исследованиях животных и клинических испытаниях этапа II, вызывает его эффект, стимулирующий миелинацию. Недавние исследования

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is growing in prevalence; yet, treatments that can reverse the progression of the disease are still needed. One strategy that has shown promise for reversing MS is remyelination by inhibiting the M1 receptor, a member of the muscarinic acetylcholine receptor (mAChR) family. Antagonizing the M1 mAChR is believed to be the mechanism by …

Promoting remyelination in multiple sclerosis: current drugs and future prospects.

Myelin destruction due to inflammatory oligodendrocyte cell damage or death in conjunction with axonal degeneration are among the major hist … ing demyelination outweighs inflammation. This has sparked great interest in the development of new remyelination therapies aimed at reversing the neurodegenerative damage observed in this disease. Remyelination as a result of oligodendrocyte production from oligodendrocyte precursor cells (OPCs) is considered a promising potential target for the treatment of a …

Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination.

Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence o…

Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation.

Remyelination is a critical step for functional nerve regeneration. Here we show that fibrin deposition in the peripheral nervous system after injury is a key regulator of remyelination. After sciatic nerve crush, fibrin is deposited and its clearance correlates with remyelination. Fibrin induces phosphorylation of ERK1/2 and production of p75 NGF low-affinity receptor in Schwann cells and maintains them in a nonmyelinating state, suppresses fibronectin production, and prevents synthesis of myelin proteins. In mice depleted of fibrin(ogen), remyelination of myelinated axons is accelerated due …

Effects of quetiapine on cognitive functioning in schizophrenia: evidence for the remyelination hypothesis?

Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitiv … ntative findings do not provide evidence for the hypothesis that polygenic estimates of hippocampal remyelination capacities influence the association between QET and cognitive performance in SCZ.

The Neurovascular Niche: A Gathering Venue for Neuroinflammation and Remyelination in Multiple Sclerosis.

In the central nervous system (CNS), the tissue microenvironment is continuously monitored and regulated to secure the unobstructed function … eatments. Nevertheless, regenerative interventions aiming at enhancing and restoring the endogenous remyelination potential of the CNS, driven by the abundant Oligodendrocyte Progenitor Cells (OPCs), have not been successfully developed so far. Here, we will review key information on the structure of the NVN, and we will summarize the evidence on the role of in …

Temporal dynamics of CNS cholesterol esters correlate with demyelination and remyelination.

Elevated cholesterol ester levels have been observed in the CNS of patients with neurological diseases, yet the source of cholesterol ester accumulation and whether it is directly linked to demyelination remains undefined. This study investigates the temporal dynamics of cholesterol esters using the Plp1-iCKO-Myrf mouse model, which features distinct phases of demyelination and remyelination. Our findings reveal that cholesterol ester levels increased with demyelination in both the brain and the spinal cord. In the brain, cholesterol esters declined to normal levels during remyelination, where…

Spatial lipidomics reveals demyelination and remyelination dynamics in the mouse brain.

Myelin pathology in demyelinating diseases is accompanied by lipid remodeling that remains challenging to characterize at the spatial level using traditional mass spectrometry. We developed an optimized AP-MALDI-Orbitrap MSI pipeline, incorporating sample preparation improvements and mass recalibration, to investigate lipid dynamics in the cuprizone (CPZ) mouse model of demyelination. Dual-modality, untargeted lipid profiling was performed to map spatially resolved lipid alterations during demyelination and spontaneous remyelination in two key brain areas of male mice: corpus callosum (CC) and…

Анализ биологических возрастных показателей в ходе клинических испытаний на ремимилинацию.

Улучшение ремонта миелина CNS (восстановление) является перспективной стратегией предотвращения нейродегенерации и связанной с этим постепенной инвалидности при множественном склерозе. Ремиэлизация становится неэффективной в более старшем хронологическом возрасте, но связь между показателями биологического возраста и воспоминанием ранее не описывалась в клинической когорте. Здесь, мы расследовали two - показатели биологического возраста среди участников Кембриджского центра миелинового ремонта One bexarotone: МРТ (BAMRI) и основанный на крови биологический возраст (BABlood). У людей с радиолог

Совпадение в аннотации оригинала
Enhancing CNS myelin repair (remyelination) is a promising strategy to prevent neurodegeneration and associated progressive disability in multiple sclerosis. Remyelination becomes inefficient with older chronological age, but the relationship between measures of biological age and remyelination has not been previously described in a clinical cohort. Here, we…

Characterization of Glial Populations in the Aging and Remyelinating Mouse Corpus Callosum.

Cells in the white matter of the adult brain have a characteristic distribution pattern in which several cells are contiguously connected to each other, making a linear array (LA) resembling pearls-on-a-string parallel to the axon axis. We have been interested in how this pattern of cell distribution changes during aging and remyelination after demyelination. In the present study, with a multiplex staining method, semi-quantitative analysis of the localization of oligodendrocyte lineage cells (oligodendrocyte progenitors, premyelinating oligodendrocytes, and mature oligodendrocytes), astrocyte…

TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination.

Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid drop…

New targets and therapeutics for neuroprotection, remyelination and repair in multiple sclerosis.

INTRODUCTION: Immunotherapies for multiple sclerosis (MS) significantly decrease the risk of new relapses. However, the chronic compartmentalized inflammation and neurodegeneration that define progressive MS are not prevented by these therapies and so significant damage to the brain and spinal cord and resulting disability ensues. Hence, the possibility of combining current immunotherapies with neuroprotective, remyelinating or regenerative therapies should be pursued. AREAS COVERED: This article sheds light on neuroprotective, remyelination and neurorepair strategies for MS, the numerous mec…

Inhibitory milieu at the multiple sclerosis lesion site and the challenges for remyelination.

Regeneration of myelin, following injury, can occur within the central nervous system to reinstate proper axonal conductance and provide trophic support. Failure to do so renders the axons vulnerable, leading to eventual degeneration, and neuronal loss. Thus, it is essential to understand the mechanisms by which remyelination or failure to remyelinate occur, particularly in the context of demyelinating and neurodegenerative disorders. In multiple sclerosis, oligodendrocyte progenitor cells (OPCs) migrate to lesion sites to repair myelin. However, during disease progression, the ability of OPCs…

The Spatial and Temporal Characters of Demyelination and Remyelination in the Cuprizone Animal Model.

Multiple sclerosis (MS) is the most common central nervous system disease due to demyelination in young adults, and currently, there is no cure. Some experimental animal models were generated to mimic specific aspects of MS pathological characteristics. Among them, the cuprizone (CPZ)-induced mouse demyelination model presents heterogeneous pathologies with both focal and diffuse lesions. Considering that MS is a progressive disease, it is important to study the spatial and temporal characters of de- and remyelination in MS animal models. However, such data especially in some brain regions suc…

The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination.

BACKGROUND: In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely. OBJECTIVE: A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules. METHODS: In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced demyeli…

The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model.

Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction…