Результаты поиска

Why repair fails in AQP4-IgG-positive neuromyelitis optica spectrum disease: an astrocyte-centered framework for remyelination and neuroaxonal preservation.

Aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disease (NMOSD) is an autoimmune astrocytopathy in which a single attack may cause permanent visual or neurological disability. Although targeted immunotherapies reduce relapse risk, they do not establish repair of previously injured tissue. Repair failure is framed as disruption of an astrocyte-organized environment required for glial communication, oligodendrocyte lineage progression, myelin formation, and axonal survival. Five linked barriers organize the review: loss of astrocytic homeostatic support, glial unco

Усилить ремиилизацию за счет блокада астроцитических рецепторов P2X1 в Cuprizon-Invested Demyelination Model.

Демиелинизирующие заболевания, такие, как множественный склероз (MS), представляют собой ситуации с основной особенностью первичного или вторичного повреждения миелин и олигодендроцитов (ОИ) в результате различных оскорблений, включая аутоиммунную атаку и воспаление, которые в конечном счете приводят к аксонным травмам и неврологической дисфункции. В настоящее время иммунодуляторная терапия MS оказывает весьма ограниченное воздействие на прогрессию заболеваний и долгосрочный прогноз. В связи с этим все больше внимания уделяется стратегии, нацеленной на достижение результатов в этой области. Со

Совпадение в аннотации оригинала
Demyelinating diseases such as multiple sclerosis (MS) are situations with the core feature of primary or secondary damage to myelin and oli … ATP treated astrocyte culture that overexpressed P2X1 significantly hindered the differentiation of oligodendrocyte precursor cells (OPCs) in vitro compared to CM from empty vector virus-infected astrocytes with the same treatment, suggesting the secretion of certain inhibitory factors for OPC maturation and myelination by astrocytes with upregulated P2X1 receptor expression. Ta …

Alzheimer's disease multi-ancestry genome-wide interaction and stratified study with smoking.

INTRODUCTION: Alzheimer's disease (AD) has genetic and environmental risk factors, including cigarette smoking. Gene-environment interactions may explain AD missing heritability. METHODS: Lifetime smoking data from 22,032 European ancestry and 3126 African ancestry participants from the Alzheimer's Disease Genetic Consortium and the Framingham Heart Study were used to conduct genome-wide single nucleotide polymorphism (SNP)-by-smoking interaction and smoking-stratified association studies. For top-ranked loci, brain-derived bulk and single nuclei RNA-sequencing were used for differential expr

Erinacine S, a small active component derived from Hericium erinaceus, protects oligodendrocytes and alleviates mood abnormalities in cuprizone-exposed rodents.

Hericium erinaceus mycelium extract (HEM), containing erinacine A (HeA) and erinacine S (HeS), has shown promise in promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), crucial for myelin production in the central nervous system (CNS). The main aim of this study was to characterize the protective effects of HEM and its components on OLs and myelin in demyelinating rodents by exposure to cuprizone (CPZ), a copper chelating agent commonly used to induce demyelination in the corpus callosum of the brain. Rats were fed by CPZ-containing diet a…

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha.

Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI) … nravel the role of PGC1α in exercise-induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin-related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve condu …

Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats.

Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (α-asaronol), a major compound isolated from the Chinese medicinal herb Acorus gramineus by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of α-asaronol on myelination in

rHIgM22 enhances remyelination in the brain of the cuprizone mouse model of demyelination.

Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal. Previous studies have sh…

Adenosine 2A receptor drives microglial efferocytosis to accelerate white matter repair and functional recovery after stroke.

Although reperfusion therapy effectively restores blood flow to occluded brain arteries after ischemic stroke, many patients develop persistent white matter injury, a major contributor to long-term neurological disability. Currently, there are few approved clinical therapies that specifically target white matter repair to enhance functional recovery after stroke. We demonstrated that microglial adenosine 2A receptor (A2AR) is essential for spontaneous white matter regeneration after ischemic injury in mice. Deletion of A2AR in microglia specifically impaired chronic-phase repair without alteri

Reduction in miR-219 expression underlies cellular pathogenesis of oligodendrocytes in a mouse model of Krabbe disease.

Krabbe disease (KD), also known as globoid cell leukodystrophy, is an inherited demyelinating disease caused by the deficiency of lysosomal galactosylceramidase (GALC) activity. Most of the patients are characterized by early-onset cerebral demyelination with apoptotic oligodendrocyte (OL) death and die before 2 years of age. However, the mechanisms of molecular pathogenesis in the developing OLs before death and the exact causes of white matter degeneration remain largely unknown. We have recently reported that OLs of twitcher mouse, an authentic mouse model of KD, exhibit developmental defec

Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.

BACKGROUND: White matter injury (WMI) is the most prevalent lesion in cerebral small vessel disease and a major contributor to cognitive decline. Recent studies have highlighted the critical role of gut microbiota in regulating brain disorders. However, the role of gut microbiota in WMI-related cognitive decline remains unclear. METHODS: A bilateral carotid artery stenosis (BCAS) mouse model was established to mimic WMI and related cognitive decline. Fecal microbiota transplantation was employed to verify the causal relationship between gut microbiota dysbiosis and WMI. 16 S rRNA gene sequenci

beta-Amyloid protein precursor in Microcebus murinus: genotyping and brain localization.

Senile plaques characterized by beta-amyloid protein (A beta) deposits around dystrophic neurites and glial cells are more abundant in the cerebral cortical parenchyma of Alzheimer's disease (AD) patients than in the aged population. Four different mutations in the amyloid precursor protein (APP) gene have been directly involved in a few cases of familial AD with early onset (before 60 years). Previous studies have shown that Microcebus murinus, a nonhuman primate, also develops analogous deposits of A beta in the cortical parenchyma and blood vessel walls in the brain. Sequence analysis of ex

Comparison of the neuropoietic activity of gene-modified versus parental mesenchymal stromal cells and the identification of soluble and extracellular matrix-related neuropoietic mediators.

INTRODUCTION: Transplanting mesenchymal stromal cells (MSCs) or their derivatives into a neurodegenerative environment is believed to be beneficial because of the trophic support, migratory guidance, immunosuppression, and neurogenic stimuli they provide. SB623, a cell therapy for the treatment of chronic stroke, currently in a clinical trial, is derived from bone marrow MSCs by using transient transfection with a vector encoding the human Notch1 intracellular domain. This creates a new phenotype, which is effective in experimental stroke, exhibits immunosuppressive and angiogenic activity equ

Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair.

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2% Cup for 6 weeks to induce detectable neuroinfl

Altered gene transcription linked to astrocytes and oligodendrocytes in frontal cortex in Creutzfeldt-Jakob disease.

Targeted expression of genes coding for proteins specific to astrocytes, oligodendrocytes and myelin was performed in frontal cortex area 8 of Creutzfeldt-Jakob disease methionine/methionine and valine/valine (CJD MM1 and VV2, respectively) compared with controls. GFAP (glial fibrillary acidic protein) mRNA was up-regulated whereas SLC1A2 (solute carrier family 1 member 2, coding for glutamate transporter 1: GLT1), AQ4 (aquaporin 4), MPC1 (mitochondrial pyruvate carrier 1) and UCP5 (mitochondrial uncoupled protein 5) mRNAs were significantly down-regulated in CJD MM1 and CJD VV2, and GJA1 (con

Single-cell RNA-seq analysis of the brainstem of mutant SOD1 mice reveals perturbed cell types and pathways of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons throughout the brain and spinal cord progressively … ogenesis (astrocytes, oligodendrocytes, neurons), synapse organization and transmission (microglia, oligodendrocyte precursor cells, and neuronal subtypes), and mitochondrial function (uncharacterized cell populations). Other cell-type specific processes altered in SOD1 mutant brainstem include those from motor neurons (axon regeneration, voltage-gated sodium and potassium chann …

Remyelination: cellular and gene therapy.

Dysfunctional myelination or oligodendroglial abnormalities play a prominent role in a vast array of pediatric neurological diseases of genetic, inflammatory, immunological, traumatic, ischemic, developmental, metabolic, and infectious causes. Recent advances in glial cell biology have suggested that effective remyelination strategies may, indeed, be feasible. Evidence for myelin repair is accumulating in various experimental models of dysmyelinating and demyelinating disease. Attempts at remyelination have either been directed towards creating myelin de novo from exogenous sources of myelin-e

Identification of CD74-Positive Antigen-Presenting Glioma Cells in Primary Human Tumors and Murine Models of NF1 High-Grade Glioma.

Compared with the general population, individuals with neurofibromatosis type 1 have a 50-fold higher risk of developing a high-grade glioma (HGG) in their lifetime. Despite improved understanding of the molecular and cellular drivers of these neoplasms, we have yet to translate this knowledge into therapies that improve overall survival. One limitation has been the paucity of in vivo models for drug testing within this population. We generated three distinct glioma stem cell lines from HGGs arising in mice with Nf1 and Trp53 mutations in cis (NPcis) and characterized the allografts resulting

The dual role of the PI3K/AKT/mTOR axis in glial cell survival and neuroinflammation.

Multiple sclerosis is characterized by a triad of inflammation, demyelination, and neurodegeneration, yet current disease-modifying therapies are limited in their ability to halt progressive neurodegeneration or promote remyelination. The PI3K/AKT/mTOR signaling pathway is a master regulator of these divergent cellular processes and therefore represents a biological paradox in multiple sclerosis. In the pathogenic facet of the disease, activation of this axis supports the differentiation and effector functions of pro-inflammatory T- and B-cells and contributes to inflammatory programs in micro

Spatiotemporal profiling of white matter lesions and their contribution in the pathologies of Parkinson's disease animal models.

Increasing evidence has identified significant white matter lesions (WMLs) in Parkinson's disease (PD) patients. However, the complex relati … impairments, preceded those caused by nigrostriatal injury. Further in vitro studies revealed that oligodendrocyte precursor cells (OPCs) dysfunction caused by 1-methyl-4-phenylpyridinium (MPP⁺) or α-Syn could induce dopaminergic axonal breakage and neuronal damage, confirming myelination disorder promoted dopaminergic neuronal degeneration. This finding was certified in additi …

Molecular and neuropathological determinants of neuronal dysfunction in Alzheimer's disease.

The biological basis of neuronal excitatory/inhibitory (E/I) imbalance in Alzheimer's disease (AD) remains unclear. Using a comprehensive co … Lastly, the estimated E/I imbalances in AD aligned with whole-brain distributions of microglia and oligodendrocyte precursor cells, suggesting that spatial cellular organization contributes to vulnerability to neuronal dysfunction. Overall, this study provides critical insights into the cellular, molecular, and neuropathological signatures of circuit-level dysfunction in AD.