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Хромогранин B действует как нейронный паракринный фактор, провоцирующий апоптоз олигодендроцита.

Известно, что различные растворимые факторы, такие, как подстрекательские цитокины и автоантитела, скрытые активированными микроглией, макрофагами и астроцитами, способствуют смерти линейных клеток олигодендроцита (OL), в том числе ОН и НО-прекурсорных клеток (OLC), в центральной нервной системе во время демиелинации множественных склерозов. Однако роль факторов, скрытых от нейронов, в смерти клеток ОЛ по-прежнему недостаточно изучена. Хромогранин В (Чгб), критический белок для скрытого гранула в нейроэндокринных клетках, также выражается и отделяется от нейронов. В этом исследовании мы изучил

The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation.

Neuroinflammation is a blanket term that describes the body's complex inflammatory response in the central nervous system (CNS). It encompas … stem cell (hPSC)-derived glia and supporting cells within the CNS, including astrocytes, microglia, oligodendrocyte precursor cells, pericytes, and endothelial cells, to describe the state of the field and hope for future discoveries. hPSC-derived cells offer an expanded potential to study the pathobiology of neuroinflammation and immunomodulatory cascades that impact disease pr …

Mouse Models of Pediatric Supratentorial High-grade Glioma Reveal How Cell-of-Origin Influences Tumor Development and Phenotype.

High-grade glioma (HGG) is a group of primary malignant brain tumors with dismal prognosis. Whereas adult HGG has been studied extensively, childhood HGG, a relatively rare disease, is less well-characterized. Here, we present two novel platelet-derived growth factor (PDGF)-driven mouse models of pediatric supratentorial HGG. Tumors developed from two different cells of origin reminiscent of neural stem cells (NSC) or oligodendrocyte precursor cells (OPC). Cross-species transcriptomics showed that both models are closely related to human pediatric HGG as compared with adult HGG. Furthermore, a…

Frozen in Place: Proximity Labeling Maps Glial Interactomes Across Cell States.

Glial cells, including radial glia, oligodendrocyte precursor cells (OPCs), oligodendrocytes, astrocytes, and microglia, are active and dynamic regulators of central nervous system (CNS) development, homeostasis, and disease. Through extensive interactions with neurons, other glial populations, and the vasculature, they form highly specialized communication networks that are essential for normal brain function. While transcriptomic approaches have revealed extensive glial heterogeneity and enabled the prediction of putative signaling networks, a critical challenge remains in validating and tra…

Inhibiting H3K18 lactylation in microglia aggravates white matter injury after intracerebral hemorrhage in mice.

BACKGROUND: White matter injury (WMI) is a key contributor to long-term cognitive deficits following intracerebral hemorrhage (ICH), yet its … up to 28 days post-ICH using the Morris Water Maze test. RESULTS: H3K18la levels were elevated and oligodendrocyte precursor cells (OPCs) increased in the perihematomal region post-ICH. A-485 administration significantly reduced microglial H3K18la, concomitantly suppressed OPC recruitment to the injury site, and exacerbated both WMI and long-term cognitive impairment. In contra …

Pre-activation status impacts regenerative potential of oligodendrocyte progenitors in an LPS-exposed animal model.

INTRODUCTION & AIMS: Optimal neural activity in the central nervous system relies on the myelin sheath formed by oligodendrocytes. During demyelination, changes in the microenvironment can activate oligodendrocyte precursor cells (OPCs) and induce them to generate new oligodendrocytes. However, different demyelination models employ distinct pathways, targeting different cells and cytokines; these, in turn, have varying effects on OPCs. Therefore, it is reasonable to assume that OPCs derived from different pathologic environment may exhibit functional differences. This study aims to investigate…

Gasdermin D activation in oligodendrocytes and microglia drives inflammatory demyelination in progressive multiple sclerosis.

Neuroinflammation coupled with demyelination and neuro-axonal damage in the central nervous system (CNS) contribute to disease advancement in progressive multiple sclerosis (P-MS). Inflammasome activation accompanied by proteolytic cleavage of gasdermin D (GSDMD) results in cellular hyperactivation and lytic death. Using multiple experimental platforms, we investigated the actions of GSDMD within the CNS and its contributions to P-MS. Brain tissues from persons with P-MS showed significantly increased expression of GSDMD, NINJ1, IL-1β, and -18 within chronic active demyelinating lesions compar

Recent Advances in Live Imaging of Cells of the Oligodendrocyte Lineage.

Myelination is an important process that takes place also in the periphery during development and in the adulthood. Myelin serves as an electric isolator for axons, leading to a fast conduction of the action potential, and provides trophic support for the axon, both aspects highly important for the proper function of the nervous system. In the central nervous system, myelination starts shortly after birth and cells from the oligodendrocyte lineage tightly regulate this process during the whole life span. Initially, it was thought that under physiological conditions myelin generation only occur

Transcriptional Regulator ZEB2 Is Essential for Bergmann Glia Development.

Bergmann glia facilitate granule neuron migration during development and maintain the cerebellar organization and functional integrity. At present, molecular control of Bergmann glia specification from cerebellar radial glia is not fully understood. In this report, we show that ZEB2 (aka, SIP1 or ZFHX1B), a Mowat-Wilson syndrome-associated transcriptional regulator, is highly expressed in Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia specification, and develop cerebellar cortical la

From synapse to sheath: how OPCs couple neural activity to adaptive myelination and behavioral plasticity.

Oligodendrocyte precursor cells (OPCs) are abundant progenitor cells in the central nervous system. Unlike mature oligodendrocytes, OPCs form functional synapses with neurons and respond to both glutamatergic and GABAergic signals. Glutamate activates calcium-permeable AMPA receptors on OPCs, generating local Ca2+ signals that regulate myelin sheath formation and stabilization. In parallel, GABAergic signaling modulates OPC proliferation and differentiation through both calcium-dependent and transcriptional mechanisms. Activity-dependent myelination driven by OPCs contributes directly to neura…

In Vivo Monitoring of Fabp7 Expression in Transgenic Zebrafish.

In zebrafish, like in mammals, radial glial cells (RGCs) can act as neural progenitors during development and regeneration in adults. However, the heterogeneity of glia subpopulations entails the need for different specific markers of zebrafish glia. Currently, fluorescent protein expression mediated by a regulatory element from the glial fibrillary acidic protein (gfap) gene is used as a prominent glia reporter. We now expand this tool by demonstrating that a regulatory element from the mouse Fatty acid binding protein 7 (Fabp7) gene drives reliable expression in fabp7-expressing zebrafish gl

High-Dose Neural Stem/Progenitor Cell Transplantation Increases Engraftment and Neuronal Distribution and Promotes Functional Recovery in Rats after Acutely Severe Spinal Cord Injury.

Severe spinal cord injury (SCI) leads to permanent, complete paraplegia and places considerable mental and economic burdens on patients, compared with mild to moderate SCI. However, the dose-related effects of the neural stem/precursor cell (NSPC) transplantation on the injury microenvironment, NSPC survival, axonal growth, neuronal distribution, the composition of neurons, oligodendrocytes, and astrocytes in the lesion area and functional recovery have not yet been quantitatively evaluated in the context of severe SCI. In our study, we acutely transplanted 2.5 × 104 or 1.5 × 105 NSPCs/μl into

Lead (Pb) exposure results in cell type specific changes in the mouse retina and optic nerve.

Chronic exposure to lead (Pb) is known to cause deficits in neuronal function across the nervous system, including the visual nervous system … used to quantify changes in cell density of retinal ganglion cells (RGCs), oligodendrocytes (OLs), oligodendrocyte precursor cells (OPCs), and myelin structure. Following Pb exposure, we observed a small, but significant reduction in the cell density of RGCs in the retina. However, we found no significant changes in branch thickness or coverage of retinal vasculature following …

RXR Gamma Enables Oligodendrocyte Differentiation by Suppressing Sonic Hedgehog Signaling.

Overcoming remyelination failure is one of the main targets in therapeutic strategies for multiple sclerosis. This process requires the differentiation of oligodendrocyte precursor cells (OPCs) to mature myelinating oligodendrocytes (OLs), a process known to be controlled by thyroid hormone, nuclear receptors, and sonic hedgehog (SHH). Retinoid X receptor gamma (RXRg) is one of the nuclear receptors acting as a positive regulator of remyelination, but little is known about its mechanisms of function. Using transcriptomic and pharmacological analysis of primary neural stem cell-derived OPCs, we…

Spinal Cord Injury Remyelination: Pathways to Therapies.

Spinal cord injury (SCI) is a debilitating condition that results from a culmination of acute and chronic damage to neural tissue, specifically the myelin sheath, thus impacting neurons' abilities to synergistically perform their physiological roles. This review explores the molecular underpinnings of myelination, demyelination, and remyelination, emphasizing the role of oligodendrocyte progenitor cells (OPCs), astrocytes, and microglia in physiological, and pathophysiological, healing. Furthermore, we link these processes with emerging therapeutic strategies currently under investigation in a

Prominent elevation of extracellular matrix molecules in intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the predominant type of hemorrhagic stroke with high mortality and disability. In other neurol … s disease and staining controls. Tissue culture was employed to examine the roles of ECM members on oligodendrocyte precursor cells (OPCs). RESULTS: Among the lectican chondroitin sulfate proteoglycan (CSPG) members, neurocan but not aggrecan, versican-V1 and versican-V2 was prominently expressed in perihematomal tissue and lesion core compared to the contralateral area in muri …

Umbilical cord blood cells for the treatment of preterm white matter injury: Potential effects and treatment options.

Preterm birth is a global public health problem. A large number of preterm infants survive with preterm white matter injury (PWMI), which leads to neurological deficits, and has multifaceted etiology, clinical course, monitoring, and outcomes. The principal upstream insults leading to PWMI initiation are hypoxia-ischemia and infection and/or inflammation and the key target cells are late oligodendrocyte precursor cells. Current PWMI treatments are mainly supportive, and thus have little effect in terms of protecting the immature brain or repairing injury to improve long-term outcomes. Umbilica…

Chronic intermittent hypoxia causes oligodendrocyte lineage cell dysfunction and cognitive deficits in a murine model: Partial reversal by reoxygenation treatment.

Obstructive Sleep Apnea (OSA) is a common sleep-related respiratory disorder characterized by chronic intermittent hypoxia (CIH). However, t … memory. Mice exposed to CIH exhibited reduced myelin density, accompanied by decreased branching of oligodendrocyte precursor cells (OPCs), as well as reduced numbers of OPCs and oligodendrocytes. We further revealed that CIH impaired myelin plasticity, which may be linked to hyperactivated autophagy in these cells. Furthermore, CIH exposure caused synapse loss and altered neuro …

Лечение метаформина уменьшает воспаление, дисмиелинацию и остроту заболеваний в мышиной модели множественного склероза, экспериментального аутоиммунного энцефаломиелита.

Множественный склероз (MS) — аутоиммунная болезнь, характеризующаяся воспалением, смертью или повреждением олигодендроцитов и аксоновой дегенерацией. Нынешние методы лечения синдрома MS являются неаккуратными, сопряженными с нежелательными побочными эффектами и дорогостоящими, что подчеркивает необходимость расширения терапевтических возможностей для пациентов. Существует большой интерес к разработке мер вмешательства с использованием лекарственных средств или терапевтических средств в целях сокращения числа симптомов и защиты ранее существовавшего миелина. Метформин является хорошо терпимым л

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation, death or damage of oligodendrocytes, and axonal degeneration … Here, we investigated whether metformin administration could improve functional outcomes, modulate oligodendrocyte precursor cells (OPCs), and reduce inflammation in a well-established mouse model of MS- experimental autoimmune encephalomyelitis (EAE). Male and female mice received metformin treatment at the time of EAE induction ("acute") or upon presentation of disease sympto …