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Oligodendrocyte precursor cells facilitate neuronal lysosome release.

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse …

Pathological potential of oligodendrocyte precursor cells: terra incognita.

Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many ways from other glial cells. OPCs have been classically studied in the context of their remyelinating capacity. Recent studies, however, revealed that aOPCs not only contribute to post-lesional remyelination but also play diverse crucial roles in multiple neurological diseases. In this review we briefly present the physiology of aOPCs and summarize current knowledge of the beneficial and detrimental roles of aOPCs in different CNS…

Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan.

Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system responsible for generating myelinating oligodendrocytes throughout life. However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination and adaptive myelination during learning. To determine how aging influences OPCs, we generated a transgenic mouse line (Matn4-mEGFP) and performed single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescenc

Oligodendrocyte precursor cells as a therapeutic target for demyelinating diseases.

The mechanisms regulating differentiation of multipotent oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes (OLs) are critical to our understanding of myelination and remyelination. Following acute demyelination in the central nervous system, adult OPCs migrate to the injury site, differentiate into OLs and generate new myelin sheaths. A common feature of regenerative processes is the fact that remyelination efficiency declines with aging and, accounts for the observation that chronic demyelinating diseases like multiple sclerosis (MS) are characterized by an ineffective remy

Autophagy in Multiple Sclerosis: Phagocytosis and Autophagy of Oligodendrocyte Precursor Cells.

Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 m … hese autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of gr …

Role of Perivascular Oligodendrocyte Precursor Cells in Angiogenesis After Brain Ischemia.

Background Oligodendrocyte precursor cells ( OPC s) regulate neuronal, glial, and vascular systems in diverse ways and display phenotypic heterogeneity beyond their established role as a reservoir for mature oligodendrocytes. However, the detailed phenotypic changes of OPC s after cerebral ischemia remain largely unknown. Here, we aimed to investigate the roles of reactive OPC s in the ischemic brain. Methods and Results The behavior of OPC s was evaluated in a mouse model of ischemic stroke produced by transient middle cerebral artery occlusion in vivo. For in vitro experiments, the phenotypi…

Expression of Oligodendrocyte Precursor Cell Markers in Canine Oligodendrogliomas.

Oligodendroglioma is a common brain tumor in dogs, particularly brachycephalic breeds. Oligodendrocyte precursor cells (OPCs) are suspected to be a possible origin of oligodendroglioma, although it has not been well elucidated. In the present study, 27 cases of canine brain oligodendrogliomas were histologically and immunohistochemically examined. The most commonly affected breed was the French Bulldog ( n = 19 of 27, 70%). Seizure was the most predominant clinical sign ( n = 17 of 25, 68%). The tumors were located mainly in the cerebrum, particularly in the frontal lobe ( n = 10 of 27, 37%). …

Oligodendrocyte Precursor Cells Shape Retinogeniculate Refinement Via a CHD8-Dependent Phagocytic Pathway.

PURPOSE: The most robust functional synaptic refinement in the dorsal lateral geniculate nucleus (dLGN) occurs around the time of eye openin … synaptic development by controlling phagocytic glial function. RESULTS: Our findings revealed that oligodendrocyte precursor cells (OPCs) act as the major cells responsible for synaptic phagocytosis during this stage, and their ablation leads to excessive excitatory synapses in the dLGN. Single-cell sequencing analysis identified a distinct OPC subpopulation exhibiting high pha …

Global O-GlcNAcome Identifies O-GlcNAcylated Proteins Regulating Oligodendrocyte Precursor Cells Differentiation.

Oligodendrocyte precursor cells (OPCs) differentiate into myelinating oligodendrocytes to form the myelin sheaths essential for neural function, a process frequently compromised during aging and in diseases like multiple sclerosis. However, the regulatory landscape of myelination remains incompletely understood. Here, we perform a comprehensive proteomic analysis of the O-GlcNAcome in postnatal day 0 mouse OPCs, identifying 165 O-GlcNAcylation sites across 118 proteins. These proteins are mostly nuclear and characterized by single-site modifications. Comparative analysis identifies 74 novel si…

Canonical and non-canonical roles of oligodendrocyte precursor cells in mental disorders.

Psychiatric research has shifted from a neuroncentric view to understanding mental disorders as disturbances of heterogeneous brain networks. Oligodendrocyte precursor cells (OPCs)- actively involved in the modulation of neuronal functions - are altered in psychiatric patients, but the extent and related consequences are unclear. This review explores canonical and non-canonical OPC-related pathways in schizophrenia, bipolar disorder, post-traumatic stress disorder, and depression in humans, highlighting potential mechanisms shared across diagnostic entities.

Roles of Ion Channels in Oligodendrocyte Precursor Cells: From Physiology to Pathology.

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration,…

A New Acquaintance of Oligodendrocyte Precursor Cells in the Central Nervous System.

Oligodendrocyte precursor cells (OPCs) are a heterogeneous multipotent population in the central nervous system (CNS) that appear during embryogenesis and persist as resident cells in the adult brain parenchyma. OPCs could generate oligodendrocytes to participate in myelination. Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells, the myelin-independent roles of OPCs, and the regulatory mechanism of OPC development. In this review, we will explore the updated knowledge on OPC identity, their multifaceted roles in the CNS in health an…

Compromised Lactate Efflux Renders Vulnerability of Oligodendrocyte Precursor Cells to Metabolic Stresses.

Among the brain cells, oligodendrocyte progenitor cells (OPCs) are the most vulnerable in response to hypoxic and ischemic insults, of which the mechanism remains unknown. Brain cells are known to import or export lactate via differentially expressed monocarboxylate transporters (MCTs) to maintain energy metabolism and pH homeostasis. The present study aims to determine the role of MCT1 in the high vulnerability of OPCs. Here we show that a mild ischemic condition equivalent to ischemic preconditioning caused detectable loss of OPCs. MCT1, which is primarily expressed in oligodendrocyte lineag

Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-β signaling.

Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondl…

Sex-specific differences in transcriptomic profiles and cellular characteristics of oligodendrocyte precursor cells.

The susceptibility to neurological and psychiatric disorders reveals sexual dimorphism in the structure and function of human brains. Recent evidence has also demonstrated the sex-related differences in cellular components of the brain, including neurons, microglia, astrocytes, and endothelial cells. Oligodendrocyte precursor cells (OPCs) regulate the neuronal system in various ways and play crucial roles in brain homeostasis beyond their well-known role as a reservoir for mature oligodendrocytes. Although recent studies have shown regional diversities and heterogeneities of OPCs, sex-related …

Downregulation of P2X7 receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia.

Oligodendrocyte precursor cells (OPCs) are the predominant oligodendrocyte-lineage stage in the cerebral hemispheres of neonatal rat. Prior studies have shown that OPCs are highly vulnerable to hypoxic-ischemic injury, yet the mechanisms are not well understood. P2X(7) receptor (P2X(7)R) is an ATP-gated ion channel that has unusual properties and plays very complex roles in a variety of neuropathologic conditions. However, little is known about the involvement of P2X(7)R in OPCs development and injury. The present study was aimed at examining the presence of P2X(7)R in OPCs and evaluating the …

Purification and characterization of adult oligodendrocyte precursor cells from the rat optic nerve.

Oligodendrocyte precursor cells (OPCs) persist in substantial numbers in the adult brain in a quiescent state suggesting that they may provide a source of new oligodendrocytes after injury. To determine whether adult OPCs have the capacity to divide rapidly, we have developed a method to highly purify OPCs from adult optic nerve and have directly compared their properties with their perinatal counterparts. When cultured in platelet-derived growth factor (PDGF), an astrocyte-derived mitogen, perinatal OPCs divided approximately once per day, whereas adult OPCs divided only once every 3 or 4 d. …

Using Acutely Dissociated and Purified Oligodendrocyte Precursor Cells for High-Throughput Drug Screening to Identify Compounds that Promote Oligodendrocyte Differentiation.

Multiple sclerosis (MS) is an autoimmune disease that involves an immune-mediated inflammatory response in the central nervous system and optic nerve resulting in demyelination and neural degeneration, the cause of which is unknown. The adult central nervous system has the capacity to remyelinate axons by generating new oligodendrocytes (OLs). To identify clinical candidate compounds that may promote remyelination, we have developed a high-throughput screening (HTS) assay to identify compounds that promote the differentiation of oligodendrocyte precursor cells (OPCs) into OLs. Using acutely di…

Amyloid-β suppresses oligodendrocyte differentiation in adult oligodendrocyte precursor cells (OPCs), with inflammatory gene changes distinguishing it from developmental OPCs.

BackgroundAlzheimer's disease (AD) involves white matter deterioration, but how amyloid-β (Aβ) affects oligodendrocyte lineage cells at different maturation stages remains unclear.ObjectiveTo determine whether Aβ impairs oligodendrocyte differentiation and myelination in adult oligodendrocyte precursor cells (OPCs) and to identify molecular correlates via RNA-seq.MethodsOligodendrocyte lineage cells were examined in plaque-associated regions of 8-month-old 5x familial Alzheimer's disease (FAD) mice by immunohistochemistry. Primary OPCs from neonatal and adult rats were cultured with or without…

Построение олигодендроцитов, подобных прекурсорам, из эмбриональных фибробатластов мыши с использованием miR-7a Имитация.

ЦЕЛИ: Разработка эффективных стратегий повышения эффективности мер по ликвидации последствий по-прежнему является одной из основных терапевтических проблем в связи с такими демиелинизирующими расстройствами, как множественный склероз (МС). МикроРНК (миРНК) стали мощным регулятором клеточной судьбы. Было показано, что miR-7a , в значительной степени выражается в олигодендроцитных клетках-прекурсорах (ОПК). Цель этого исследования заключалась в изучении вопроса о том, является ли завышенное выражение мнений miR-7a :: может перепрограммировать эмбриональные фибробатласты мыши (МЭФ) в похожие на O

Совпадение в аннотации оригинала
OBJECTIVES: Developing effective strategies to enhance remyelination remains a major therapeutic challenge in demyelinating disorders such as multiple sclerosis (MS). MicroRNAs (miRNAs) have emerged as powerful regulators of cell fate. It has been shown that miR-7a is highly expressed in oligodendrocyte precursor cells (OPCs). This study aimed to investigate…