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Демиелинция производит сдвиг в населении кортикальных нейронов, которые синапсируют с каллосальными олигодендроцитными клетками.

Клетки потомства олигодендроцитов (ОРК) получают синаптическое воздействие от различных нейронов в мозгу развивающихся и взрослых. Понимание того, меняются ли нейронные популяции, которые синапируют с OPC в здоровом мозге в результате обезвоживания и/или ремиэлирования, может способствовать совершенствованию стратегий нейрозащиты или миелинового ремонта, разрабатываемых для демиелинизирующих заболеваний, таких, как множественный склероз. Чтобы изучить эту возможность, мы использовали трансгенную технологию крелокса, чтобы облегчить инфекцию ОПС модифицированным вирусом бешенства, что позволяет

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… Reviewer 1 The authors use a previously established retrograde monosynaptic labelling strategy in mice to characterise the extent of synaptic input of different neuronal populations onto oligodendrocyte precursor cells (OPCs) in the corpus callosum. …

Expression profiles of the nuclear receptors and their transcriptional coregulators during differentiation of neural stem cells.

Neural stem cells (NSCs) are pluripotent precursors with the ability to proliferate and differentiate into 3 neural cell lineages, neurons, astrocytes and oligodendrocytes. Elucidation of the mechanisms underlying these biologic processes is essential for understanding both physiologic and pathologic neural development and regeneration after injury. Nuclear hormone receptors (NRs) and their transcriptional coregulators also play crucial roles in neural development, functions and fate. To identify key NRs and their transcriptional regulators in NSC differentiation, we examined mRNA expression o

Ethanol-mediated alterations in oligodendrocyte differentiation in the developing brain.

INTRODUCTION: Alterations of white matter integrity and subsequent white matter structural deficits are consistent findings in Fetal Alcohol Syndrome (FAS), but knowledge regarding the molecular mechanisms underlying these abnormalities is incomplete. Experimental rodent models of FAS have shown dysregulation of cytokine expression leading to apoptosis of oligodendrocyte precursor cells (OPCs) and altered oligodendrocyte (OL) differentiation, but whether this is representative of human FAS pathogenesis has not been determined. METHODS: Fetal brain tissue (12.2-21.4 weeks gestation) from subje…

Inosine Treatment Attenuates White Matter Injury in Neonatal Rats Exposed to Maternal Inflammation.

Periventricular leukomalacia (PVL), a severe form of brain injury affecting premature infants, is characterized by damage to the cerebral wh … and enhanced myelination by encouraging the formation of myelin proteins and the differentiation of oligodendrocyte precursor cells (OPCs). This was evidenced by an increased number of CC-1 positive mature oligodendrocytes and a reduction in GPR17 levels, a negative regulator of OPCs differentiation. More significantly, inosine treatment not only decreased the quantity of Iba 1 …

Unraveling the role of neuregulin-mediated astrocytes-OPCs axis in the pathogenesis of age-related macular degeneration and Parkinson's disease.

Age-related macular degeneration (AMD) and Parkinson's disease (PD) are prevalent and debilitating conditions that lead to irreversible blindness and dyskinesia, respectively. Emerging evidences imply that retinal abnormalities may serve as early indicators for monitoring PD. This study endeavors to explore the complex interactions and focus on their shared molecular and pathological mechanisms. We employed a comprehensive approach by integrating single-cell RNA sequencing (scRNA-seq) datasets, obtained from dry AMD retinas and PD brain tissues, along with Weighted Gene Co-expression Network A

CYP46A1-Targeted Treatment Alleviates Long-Term White Matter Injury Following Traumatic Brain Injury by Promoting Cholesterol Metabolic Clearance and Remyelination.

AIM: Cholesterol plays a critical role in repairing white matter injury (WMI) following traumatic brain injury (TBI). The enzyme cholesterol 24-hydroxylase (CYP46A1) regulates the removal of cholesterol by converting it into 24(S)-hydroxycholesterol (24OHC). Although CYP46A1 has neuroprotective effects on various central nervous system disorders, its effect on WMI remains unclear. METHODS: Adult male C57BL/6 mice underwent controlled cortical impact to model TBI. Experiments using the CYP46A1 activator efavirenz and CYP46A1-/- mice were utilized to elucidate the function of CYP46A1. Neurologi

Targeting Remyelination in Spinal Cord Injury: Insights and Emerging Therapeutic Strategies.

INTRODUCTION: Spinal cord injury (SCI) is a severe neurological disease characterized by significant motor, sensory, and autonomic dysfunctions. SCI is a major global disability cause, often resulting in long-term neurological impairments due to the impeded regeneration and remyelination of axons. A SCI interferes with communication between the brain and the spinal cord networks that control neurological functions. Recent advancements in understanding the molecular and cellular mechanisms of remyelination have opened novel therapeutic interventions. METHOD: This review systematically sourced

Evidence of the "hit and run" characteristics of Cerebroprotein Hydrolysate-I in the treatment of neonatal HIE based on pharmacokinetic and pharmacological studies.

Hypoxic ischemic encephalopathy (HIE) is the leading cause of neonatal mortality and disability, but its treatment options are very limited and there is an urgent need to further improve treatment outcomes. The present study aims to reveal the therapeutic effects, action pattern, and potential mechanisms of Cerebroprotein hydrolysate-I (CH-I), a mixture of hydrolyzed peptides and amino acids, for the management of HIE. To simulate the complex pathogenesis of HIE more accurately, we innovatively constructed a "triple hit" neonatal HIE rat model. The efficacy of CH-1 was examined in this model,

Introducing the brain erythropoietin circle to explain adaptive brain hardware upgrade and improved performance.

Executive functions, learning, attention, and processing speed are imperative facets of cognitive performance, affected in neuropsychiatric disorders. In clinical studies on different patient groups, recombinant human (rh) erythropoietin (EPO) lastingly improved higher cognition and reduced brain matter loss. Correspondingly, rhEPO treatment of young rodents or EPO receptor (EPOR) overexpression in pyramidal neurons caused remarkable and enduring cognitive improvement, together with enhanced hippocampal long-term potentiation. The 'brain hardware upgrade', underlying these observations, includ

Hv1 proton channel facilitates production of ROS and pro-inflammatory cytokines in microglia and enhances oligodendrocyte progenitor cells damage from oxygen-glucose deprivation in vitro.

The contribution of microglial activation to oligodendrocyte precursor cell (OPC) damage in the brain is considered to be a principal pathophysiological feature of periventricular leukomalacia (PVL). Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-dependent reactive oxygen species (ROS) produced in microglia has been shown to be significantly toxic to OPCs. The voltage-gated proton channel Hv1 is selectively expressed in microglia and is essential for NOX-dependent ROS production in the central nervous system. This study aimed to investigate the effects of microglial Hv1 deficiency o

ABCA5 regulates amyloid-β peptide production and is associated with Alzheimer's disease neuropathology.

Brain cholesterol homeostasis is regulated by a group of proteins called ATP-binding cassette subfamily A (ABCA) transporters. Certain ABCA transporters regulate amyloid-β protein precursor (AβPP) processing to generate amyloid-β peptides (Aβ) and are associated with an increased risk for late-onset Alzheimer's disease (AD). ABCA5 is a little-known member of the ABCA subfamily with no known function. In this study we undertook a comprehensive analysis of ABCA5 expression in the human and mouse brains. We explored the potential role of ABCA5 in AβPP processing associated with AD pathology. ABCA

Irisin Restrains Oligodendroglial Ferroptosis to Preserve White Matter After Traumatic Brain Injury via AMPK Activation.

Traumatic brain injury (TBI) results in diffuse white matter (WM) damage, which is a major determinant of death and long-term disability. Irisin, a myokine with promising neuroprotective effects, but whether irisin modulates WM injury after TBI remains unknown. Using a controlled cortical impact (CCI) mouse model, we evaluated post-TBI irisin expression and its protective effects on neurological function and WM integrity. Multiple experimental approaches, such as RT-qPCR, Liperfluo staining, Western blot, and transmission electron microscopy, were employed to assess oligodendrocyte precursor c

Dual-Targeting miR-219 and miR-146a in Multiple Sclerosis: Bridging Myelin Repair and Neuroinflammation for Novel Therapeutic Insights.

Multiple sclerosis (MS) is a debilitating neurological disorder involving concurrent immune-mediated demyelination and progressive neurodegeneration. Although disease-modifying therapies (DMTs) effectively modulate peripheral immune responses and reduce relapse rates, they are ineffective at halting disease progression and promoting central nervous system (CNS) repair. This review outlines a new therapeutic approach that targets two important microRNAs: miR-219, which stimulates oligodendrogenesis and remyelination, and miR-146a, which regulates innate immune responses and neuroinflammation. W

Early Postnatal Neuroinflammation Produces Key Features of Diffuse Brain White Matter Injury in Rats.

BACKGROUND: Perinatal infection is a major risk factor for diffuse white matter injury (dWMI), which remains the most common form of neurological disability among very preterm infants. The disease primarily targets oligodendrocytes (OL) lineage cells in the white matter but also involves injury and/or dysmaturation of neurons of the gray matter. This study aimed to investigate whether neuroinflammation preferentially affects the cellular compositions of the white matter or gray matter. METHOD: Neuroinflammation was initiated by intracerebral administration of lipopolysaccharide (LPS) to rat p

Multiple Sclerosis and Aging: The Dynamics of Demyelination and Remyelination.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and neurodegeneration. Life expectancy and age of onset in MS patients have been rising over the last decades, and previous studies have shown that age affects disease progression. Therefore, age appears as one of the most important factors in accumulating disability in MS patients. Indeed, the degeneration of oligodendrocytes (OGDs) and OGD precursors (OPCs) increases with age, in association with increased inflammatory activity of astrocytes and microglia. Similarly, age-rel

Subacute metformin treatment reduces inflammation and improves functional outcome following neonatal hypoxia ischemia.

Hypoxia-ischemia (HI) injury is a leading cause of neonatal death and long-term disability, and existing treatment options for HI offer only modest benefit. Early intervention with the drug metformin has been shown to promote functional improvement in numerous rodent models of injury and has pleiotropic cellular effects in the brain. We have previously shown that 1 week of metformin treatment initiated 24 ​h after HI in neonatal mice resulted in improved motor and cognitive performance, activation of endogenous neural precursor cells (NPCs), and increased oligodendrogenesis. While promising, a

Neuropathologic and molecular aspects of a canine distemper epizootic in red foxes in Germany.

In the last fifteen years, an epidemic of canine distemper virus (CDV) with marked neurotropism has occurred in Europe after a longer period of endemic transmission. Many wildlife species have been infected, with red foxes (Vulpes vulpes) being particularly affected. Given that this species is assumed to mediate cross-species CDV infections to domestic and wild animals, tissue samples from foxes with confirmed CDV infection in North-Western Germany were investigated to better understand the neurotropic aspects of the disease. This analysis included histopathology, virus distribution and cell t

Intravenous infusion of iPSC-derived neural precursor cells increases acid β-glucosidase function in the brain and lessens the neuronopathic phenotype in a mouse model of Gaucher disease.

Gaucher disease (GD) is caused by GBA1 mutations leading to functional deficiency of acid-β-glucosidase (GCase). No effective treatment is available for neuronopathic GD (nGD). A subclass of neural stem and precursor cells (NPCs) expresses VLA4 (integrin α4β1, very late antigen-4) that facilitates NPC entry into the brain following intravenous (IV) infusion. Here, the therapeutic potential of IV VLA4+NPCs was assessed for nGD using wild-type mouse green fluorescent protein (GFP)-positive multipotent induced pluripotent stem cell (iPSC)-derived VLA4+NPCs. VLA4+NPCs successfully engrafted in the

Granulocyte-macrophage colony-stimulating factor signals for increased glucose uptake in human melanoma cells.

While the primary targets for granulocyte-macrophage colony-stimulating factor (GM-CSF) are hematopoietic precursors and mature myeloid cells, GM-CSF receptors (GMR) are also found on normal tissues including placenta, endothelium, and oligodendrocytes as well as certain malignant cells. The function of GMR in these nonhematopoietic cells is unknown. We studied the function of GMR in human melanoma cell lines. Six of seven cell lines tested (clones 1-5 and 3.44 of SK-MEL-131, SK-MEL-188, SK-MEL-23, SK-MEL-22, and SK-MEL-22A) expressed mRNA encoding the membrane-bound and soluble isoforms of th

Opportunities and challenges for the application of single-cell RNA sequencing and spatial transcriptomics in ischemic stroke.

Ischemic stroke (IS) is characterized by high rates of morbidity, disability and mortality. The pathological process underlying IS involves spatiotemporal dynamic responses of multiple cell types and marked cellular heterogeneity which cannot be fully elucidated using traditional bulk sequencing technologies. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have provided high-resolution tools for investigating pathological mechanisms and developing precise diagnostic and therapeutic strategies for IS. In this review, we systematically summarize the core principles, mains