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Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis.

Conflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which a … and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. T …

Stimulation of monocytes, macrophages, and microglia by amphotericin B and macrophage colony-stimulating factor promotes remyelination.

Approaches to stimulate remyelination may lead to recovery from demyelinating injuries and protect axons. One such strategy is the activatio … jury. Treatment with amphotericin B, particularly in combination with MCSF, increased the number of oligodendrocyte precursor cells and promoted remyelination within lesions; these pro-regenerative effects were mitigated in mice treated with clodronate liposomes to reduce circulating monocytes and tissue-infiltrated macrophages. Our results have identified candidates among curre …

Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke.

The present study investigates the induction of axon and myelin remodeling as a possible mechanism by which treatment of stroke with bone ma … rea. In bone marrow stromal cell-treated rats, the number of Ki-67 positive proliferating cells and oligodendrocyte precursor cells in the corpus callosum increased significantly in concert with the enhancement of the areas of the corpus callosum in both hemispheres. These results suggest that bone marrow stromal cells facilitate axonal sprouting and remyelination in the cortica …

Sex differences in progressive multiple sclerosis brain gene expression in oligodendrocytes and OPCs.

Multiple sclerosis is a neurological autoimmune disease with sex-imbalanced incidence; in the USA, the disease is more likely to affect females at a ratio of 3:1. In addition, males are more likely to have a more severe disease course at time of diagnosis. Questions about both causes and downstream effects of this disparity remain. We aim to investigate gene expression differences at a cellular level while considering sex to discover fine-scale sex disparities. These investigations could provide new avenues for treatment targeting, or treatment planning based on sex.Public single-nuclei RNA-se

Оспемифен, селективный модулятор эстрогенного рецептора, усиливает олигодендроцитную миелинизацию и резервирует нейрофункции от травм.

Недостаточность миелиногенеза в результате травм центральной нервной системы (КНС) является хорошо задокументированной патологической особенностью различных заболеваний, таких, как травма белых веществ (ВМИ) и множественный склероз (МС). Реорганизация разрешенных УЛХ лекарственных средств, способных содействовать дифференциации олигодендроцитов (ОИ), представляет собой реалистичный и осуществимый подход к ремонту и функциональному восстановлению миелина. В этом исследовании сообщается, что оспемифен, одобренный УЛХ избирательного модулятора рецептора эстрогена (SERM), в значительной степени сп

Совпадение в аннотации оригинала
Insufficient myelinogenesis following central nervous system (CNS) injuries is a well-documented pathological feature in various diseases, s … ve estrogen receptor modulator (SERM), significantly promotes the differentiation of purified mouse oligodendrocyte precursor cells (OPCs) both in cultures and on nanofibers. In neonatal mice subjected to hypoxia, ospemifene prevented hypoxia-induced myelin deficits in the developing central nervous system (CNS) and preserved neurofunctions in young adolescents, likely due to it …

Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone.

Neurons and oligodendrocyte progenitors are highly sensitive to perinatal hypoxic-ischemic injury. As accumulating evidence suggests that many insults to the human infant occur in utero, and preventing brain damage to infants in utero will prove difficult, there is strong rationale to pursue regenerative strategies to reduce the morbidity associated with developmental brain injuries. The purpose of this study was to determine whether a hypoxic-ischemic insult stimulates the neural stem/progenitor cells in the subventricular zone to generate new neurons and oligodendrocytes. Hypoxia-ischemia wa

Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination.

Myelin sheaths play important roles in neuronal functions. In the central nervous system (CNS), the myelin is formed by oligodendrocytes (OLs), which are differentiated from oligodendrocyte precursor cells (OPCs). In CNS demyelinating disorders such as multiple sclerosis (MS), the myelin sheaths are damaged and the remyelination process is hindered. Small molecule drugs that promote OPC to OL differentiation and remyelination may provide a new way to treat these demyelinating diseases. Here we report that donepezil, an acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzhe…

Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia.

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic stimuli, such as hypoxia. As mitochondrial dysfunction and metabolic dysregulation are implicated in schizophrenia and other psychiatric illnesses, these modification profiles have the potential to reveal yet another layer of protein regulation and ca

Нейротрофные факторы в множественном склерозе.

Запах воспаления и нейродегенерация, вызванные главным образом внутрипаренхимальной активацией иммунных клеток и глиарной дисфункцией, по-прежнему являются одной из основных терапевтических проблем в случае множественного склероза (MS) и в значительной степени способствуют развитию инвалидности. Текущая медикаментозная терапия, направленная на изменение состояния заболеваний, реально снижает коэффициент рецидива и, в меньшей степени, прогрессирует в развитии заболеваний, ориентируясь на периферийные иммунные клетки. В то же время они в значительной степени не решают проблемы, связанные с интри

The astrocytic TRPA1 channel mediates an intrinsic protective response to vascular cognitive impairment via LIF production.

Vascular cognitive impairment (VCI) refers to cognitive alterations caused by vascular disease, which is associated with various types of dementia. Because chronic cerebral hypoperfusion (CCH) induces VCI, we used bilateral common carotid artery stenosis (BCAS) mice as a CCH-induced VCI model. Transient receptor potential ankyrin 1 (TRPA1), the most redox-sensitive TRP channel, is functionally expressed in the brain. Here, we investigated the pathophysiological role of TRPA1 in CCH-induced VCI. During early-stage CCH, cognitive impairment and white matter injury were induced by BCAS in TRPA1-k

Single-nucleus RNA sequencing identifies transcriptomic signatures of alcohol use disorder in the human ventral tegmental area.

BACKGROUND: Alcohol use disorder (AUD) is associated with altered gene expression across diverse cell types in reward-related brain regions, … x major cell types: astrocytes, endothelial cells, mature neurons, microglia, oligodendrocytes, and oligodendrocyte precursor cells (OPCs). At thresholds of P < 0.05 and |fold change| > 2.0, we identified 547 DEGs in astrocytes, 727 DEGs in endothelial cells, 715 DEGs in mature neurons, 421 DEGs in microglia, 263 DEGs in oligodendrocytes, and 432 DEGs in OPCs. DEGs across VTA ce …

CRP Deficiency Rescues Periodontitis-Induced Hippocampal Neurogenesis Impairment by Suppressing OPC-Derived BMP4 Signaling in Rats.

Chronic periodontitis (PD) is an emerging risk factor for mental disorders, although the underlying mechanisms remain unclear. Here, we show … encing (snRNA-seq) analysis revealed that hippocampal Bmp4 expression is predominantly expressed by oligodendrocyte precursor cells (OPCs). Subsequent analyses associated CRP deficiency with enhanced functional resilience of OPCs. Critically, inhibition of the CRP-BMP4 axis restored the neuronal differentiation suppressed by PD and alleviated the associated behavioral abnormalit …

Endothelial PD-1 Regulates Vascular Homeostasis and Oligodendrogenesis during Brain Development.

Appropriate vascular and neural development is essential for central nervous system (CNS). Although programmed cell death receptor 1 (PD-1) mediates neurogenesis, its role in cerebrovascular development remains poorly understood. Here, a correlation between cerebral vessels and oligodendrocyte precursor cells (OPCs) is revealed during brain development. The ablation of endothelial PD-1 triggers cortical hypervascularization through excessive angiogenic sprouting, concomitantly driving OPC differentiation. These alterations disrupt blood brain barrier (BBB) maturation, induce dysmyelination, an…

Inhibition of SUMOylation promotes remyelination and reduces IL-17 mediated autoimmune inflammation: Novel approach toward treatment of inflammatory CNS demyelinating disease.

Small ubiquitin like modifiers (SUMO) are reversible posttranslational modifiers of intracellular proteins. In the CNS, expression of myelin … ned the expression of myelin genes and their transcription factors following culture with TAK981 in Oligodendrocyte Precursor Cells (OPC). We found that myelin basic protein (MBP), a key myelin protein, is upregulated in OPC in the presence of TAK981. We also found increased expression of transcription factors Sox10 and Myrf, which engage in the expression of MBP. In the Cuprizo …

The role of astrocyte-derived extracellular vesicles in cellular microenvironment remodeling after spinal cord injury: A study based on quantitative proteomics analysis.

After spinal cord injury (SCI), astrocytes (AS), the most abundant glial cells in the central nervous system, closely interact with other ne … ivation, decreasing neuronal apoptosis, promoting axonal growth, and facilitating the maturation of oligodendrocyte precursor cells, thereby improving motor function recovery in murine models. Conversely, RA-EVs exhibited deleterious effects, exacerbating inflammation and impeding functional recovery. CC Motif Chemokine Ligand 7 (CCL7) was identified as a critical secretory prot …

Developmental expression of FMRP in the astrocyte lineage: implications for fragile X syndrome.

One of the most common causes of mental retardation in humans, Fragile X syndrome, results from the absence of FMRP, the protein product of the FMR1 gene. In the nervous system, expression of FMRP has been thought to be confined mainly to neurons as little research has examined FMRP expression in non-neuronal lineages. We present evidence that, in addition to neuronal expression, FMRP is expressed in developing CNS glial cells in vitro and in vivo. The neurosphere assay was used to establish cultures of stem and progenitor cells from the brains of wildtype and FMRP knockout (B6.129.FMR1/FvBn)

Vascular endothelial growth factors A and C are induced in the SVZ following neonatal hypoxia-ischemia and exert different effects on neonatal glial progenitors.

Episodes of neonatal hypoxia-ischemia (H-I) are strongly associated with cerebral palsy and a wide spectrum of other neurological deficits in children. Two key processes required to repair damaged organs are to amplify the number of precursors capable of regenerating damaged cells and to direct their differentiation towards the cell types that need to be replaced. Since hypoxia induces vascular endothelial growth factor (VEGF) production, it is logical to predict that VEGFs are key mediators of tissue repair after H-I injury. The goal of this study was to test the hypothesis that certain VEGF

Провоспалительные молекулы, имплицитно связанные с множественным склерозом Divert Development of Human Oligodendrocyte Lineage Cells.

ИСТОРИЯ И ЗАДАЧИ: Олигодендроциты (ОИ) и их процессы формирования миелина теряются во время заболевания, вызванного множественным склерозом (МС), цель которого заключается в проникновении лейкоцитов и их эффектных цитокинов. Считается, что ремонт миелин зависит от набора и дифференциации ячеек потомков олигодендроцитов. До сих пор не определены основания для отказа от воспоминаний во время болезни MS. Цель этого исследования состояла в том, чтобы определить влияние на дифференциацию опухолей человека факторов некроза (ОКП) и интерферона (ИФН).Мы создали человека OPC из индуцированных плюрипоте

Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation.

The development of neuroprotective therapies is a sought-after goal. By screening combinatorial chemical libraries using in vitro assays, we identified the small molecule BN201 that promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. Moreover, BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, in

A bimodal influence of thyroid hormone on cerebellum oligodendrocyte differentiation.

Thyroid hormone (T(3)) can trigger a massive differentiation of cultured oligodendrocytes precursor cells (OPC) by binding the nuclear T(3) receptor α1 (TRα1). Whether this reflects a physiological function of TRα1 remains uncertain. Using a recently generated mouse model, in which CRE/loxP recombination is used to block its function, we show that TRα1 acts at two levels for the in vivo differentiation of OPC in mouse cerebellum. At the early postnatal stage, it promotes the secretion of several neurotrophic factors by acting in Purkinje neurons and astrocytes, defining an environment suitable