Результаты поиска

The Dual Role of Macroglia in Glaucoma: Deciphering the Contributions of Astrocytes and Müller Cells to Retinal Neurodegeneration and Neuroprotection.

Glaucoma is a leading cause of irreversible vision loss characterized by the progressive degeneration of retinal ganglion cells (RGCs) and structural and biochemical remodeling of the optic nerve head. Although lowering intraocular pressure remains the primary clinical intervention, neurodegeneration often persists, highlighting the complexity and multiple mechanisms involved in the disease's pathophysiology. In the healthy retina, astrocytes and Müller cells maintain structural integrity, homeostatic balance, and metabolic support. However, sustained pathological stress triggers reactive glio…

Novel insights into β3-adrenoceptor function in a model of retinopathy of prematurity: the contribution of astrocytes to retinal protection.

The β-adrenoceptor (β-AR) system has been implicated in the pathological angiogenesis of the retina. Of the three β-ARs, the role of β3-AR r … lity of neurotrophic factors that are otherwise impaired under hypoxia. Results from microdissected astrocytes were indicative of the possibility that astrocytes might contribute to retinal rescue. β3-AR has emerged as a potential intermediary in hypoxia-dependent neovascularization, thereby providing a rationale for exploring the causality between astrocyte …

Modeling Tay-Sachs Disease in Astrocyte-like Cells Reveals Significant Changes in the Transcriptomic Profile.

Tay-Sachs disease is a rare genetic disorder characterized by the accumulation of GM2 ganglioside in neuronal lysosomes due to deficient β-hexosaminidase A (HexA) activity. Progressive GM2 storage leads to severe neurodegeneration, including developmental delay, motor weakness, seizures, ataxia, and early death, typically by five years of age. Previous studies have elucidated several neuronal mechanisms, including apoptosis, endoplasmic reticulum stress, neuroinflammation, and demyelination, these investigations have focused almost exclusively on neurons. However, other components of the centr

APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.

Lipid droplets are dynamic cellular organelles that store neutral lipids and coordinate metabolic and stress-response pathways. In the brain, lipid droplets in glial cells, including astrocytes, have been implicated in Alzheimer's disease, but how genetic risk factors influence their composition and turnover remains poorly understood. APOE is the strongest genetic modulator of late-onset Alzheimer's disease and exists in common variants that confer decreased, neutral, or increased risk. Here we show that APOE genotype shapes the lipid droplet proteome, lipidome, and degradation dynamics in hum…

Astrocytic TRPC6 protects against cerebral ischemia-reperfusion injury by inhibiting cGAS-STING pathway.

OBJECTIVE: Cerebral ischemia-reperfusion injury (CIRI) is complicated by BBB breakdown and neuroinflammation, processes partially regulated by astrocytes. This study aimed to investigate the neuroprotective mechanism of astrocyte-specific TRPC6, focusing on elucidating its molecular link to the cGAS-STING pathway and BBB integrity. METHODS: MCAO mouse models were established, with astrocyte-specific TRPC6 overexpression achieved via stereotactic injection of AAV-GFAP-Trpc6. Neurological function, infarct volume, apoptosis, and BBB integrity (including tight junction proteins and AQP4) were sy…

A Novel Reporter Mouse for Astrocyte-Derived Extracellular Vesicles Reveals Enrichment of Cargo at Neuronal Mitochondria.

Extracellular vesicles (EVs) mediate intercellular transfer of lipids, proteins, and nucleic acids between cell types. We previously showed … comprised 13.2% ± 1.6% of total isolated EVs. In primary glial cultures, CD9-tGFP was restricted to astrocytes, localizing to vesicular compartments and cell protrusions (filopodia and cilia); 89.3% ± 2.2% of astrocyte-derived EVs were CD9-tGFP positive. In cortex, hippocampus, and cerebellum, CD9-tGFP was predominantly detected in astrocytic processes co-la …

TNFα-induced endothelial extracellular vesicles regulate astrocyte function: an integrated transcriptomic and proteomic study.

Endothelial cells and astrocytes are critical structural and functional components of the blood-brain barrier. In many neuroinflammatory diseases, endothelial cells are among the first to respond to inflammatory stimuli and release extracellular vesicles (EVs). However, whether inflammatory stimulation alters EV RNA cargo and subsequently regulates astrocyte function remains unclear. In this study, we performed integrated RNA sequencing and proteomic analyses to investigate the effects of TNFα-stimulated endothelial EVs on astrocytes. RNA profiling revealed significant alterations in EV cargo …

Neuroinflammation at the Crossroads of Neurodegeneration: The Roles of Microglia and Astrocytes in Parkinson's Disease, Alzheimer's Disease, and Multiple Sclerosis.

Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review explores the underlying mechanisms of neuroinflammation, with a focus on the roles of microglia, astrocytes, peripheral immune cell infiltration, and cytokine release. The complex interplay between oxidative stress and chronic inflammation accelerates neurodegeneration, contributing to disease progression. Microglial activation, initially protective, becomes harmful when sustained over time, driving chronic inflammation…

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 … myelination, while the detailed underlying mechanism remains unknown. Here, we report that reactive astrocytes in cuprizone-induced demyelination mice showed sustained upregulation of the expression of P2 purinergic receptor X1 (P2X1). Pharmacologic blockade of P2X1 receptor signaling by receptor-specific antagonist NF449 significantly enhanced/accelerated r …

Astrocytic Ror2-induced imbalance in brain and gut homeostasis contributes to chronic post-thoracotomy pain.

BACKGROUND: Receptor tyrosine kinase-like orphan receptor 2 (Ror2) plays an indispensable role in mediating acute and chronic pain. We previ … athecal injection of AAV2/9-GFAP-miR30-shRor2 was used to knock down in vivo Ror2 expression in ACC astrocytes. The expressions of Ror2, the polarisation of astrocytes, the synthesis of CCL2 and CXCL1 in the ACC, and the levels of gut short-chain fatty acids (SCFAs) before and after intervention were assessed by RT-PCR, western blot, double immunofluorescenc …

Astrocyte regulates neuroinflammation and myelination in BCCAO-related cognitive impairment via the PIAS1-STAT1 pathway.

Vascular dementia (VaD) ranks as the second most common form of cognitive impairment worldwide, surpassed only by Alzheimer's disease (AD), … roglial depleter PLX5622 failed to effectively rescue myelin damage and cognitive impairment, while astrocytes remained persistently activated. Analysis of the differential expression profile of astrocytes from a VaD patient brain tissue database identified Protein Inhibitor of Activated STAT1 (PIAS1) as a key regulator, which was significantly downregulated …

Amyloid Beta Regulates Astrocytic Glucose Metabolism and Insulin Signaling in Experimental Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by amyloid beta (Aβ) plaques, neuroinflammation and cognitive impairment. Metabolic disturbances, particularly brain insulin resistance, are increasingly recognized as central features of AD pathophysiology. Astrocytes, essential for brain energy metabolism, exhibit a loss of homeostatic functions in AD, possibly promoting neurodegeneration. Even though the main astrocytic glucose transporters are non-insulin dependent, insulin may regulate astroglial glucose metabolism. Our objective was to evaluate insul…

RiboTag RNA Sequencing Identifies Local Translation of HSP70 in Astrocyte Endfeet After Cerebral Ischemia.

Brain ischemia causes disruption in cerebral blood flow and blood-brain barrier integrity, which are normally maintained by astrocyte endfeet. Emerging evidence points to dysregulation of the astrocyte translatome during ischemia, but its effects on the endfoot translatome are unknown. In this study, we aimed to investigate the early effects of ischemia on the astrocyte endfoot translatome in a rodent cerebral ischemia and reperfusion model of stroke. To do so, we immunoprecipitated astrocyte-specific tagged ribosomes (RiboTag IP) from mechanically isolated brain microvessels. In mice subjecte

Deciphering Ferroptosis-Related Astrocyte Subpopulations and Diagnostic Biomarkers in Parkinson's Disease through RNA Transcriptomics.

Parkinson`s disease (PD) is the second most prevalent neurodegenerative disorder, and increasing evidence indicates that glial activation plays a significant role in ferroptosis and the subsequent neurodegeneration. In this study, we aimed to identify ferroptosis-related astrocytes exhibiting elevated inflammation scores in PD patients. The single-cell and bulk RNA transcriptomic profiles of PD samples were collected from the Gene Expression Omnibus database. We characterized seven cell types in the substantia nigra region of PD and normal samples, and discovering that astrocytes from the PD g…

Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the tr

Mechanisms of electroacupuncture-induced neuroprotection in acute stroke rats: the role of astrocyte-mediated mitochondrial transfer.

BACKGROUND: Ischemic stroke significantly threatens human health, and current treatments remain limited, necessitating novel strategies. Mitochondrial transfer between neurons represents a crucial endogenous neuroprotective mechanism. OBJECTIVE: This study investigated whether electroacupuncture enhances mitochondrial transfer from astrocytes to damaged neurons during acute cerebral ischemia, promoting neuroprotection. METHODS: A middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro were employed. Neurob…

Impact of agmatine on cerebral astrocyte reactivity, neurodegeneration, and oxidative stress in bile duct-ligated rats.

Hepatic encephalopathy (HE) is a severe neurological disorder arising from liver disease, often studied using the bile duct ligation (BDL) model. This condition leads to cholestasis, triggering oxidative stress, liver damage, and fibrosis. Agmatine (AGM), an endogenous polyamine known for its neuroprotective effects, has shown potential in treating various neurological and psychological disorders due to its anti-inflammatory and antioxidant properties. This study investigates the potential of AGM to mitigate liver and brain injury in a rat model of BDL-induced HE. Adult male Wistar rats were d

Compression injury regulates astrocyte morphology, metabolic function, and extracellular matrix modification in a 3D hydrogel.

In glaucoma, the optic nerve head (ONH) is exposed to increased biomechanical strain, impacting the resident astrocytes that maintain neural homeostasis. During disease progression astrocytes exhibit morphologic and metabolic shifts; however, the specific impact of glaucoma-related biomechanical strains on astrocyte behavior remains poorly understood. To address this, we used our previously established 3D cell-encapsulated extracellular matrix (ECM) hydrogel to investigate ONH astrocyte cellular and transcriptomic responses to varying biomechanical strain levels over time. Murine ONH astrocyte…

Senkyunolide I Improves Septicemia-Induced Brain Dysfunction via Regulating Nrf2 and Astrocyte Activity.

Senkyunolide I (Sen I) has a protective effect on the blood-brain barrier (BBB) in rats with sepsis-associated encephalopathy (SAE). This study investigated whether Sen I regulates Nrf2 to ameliorate sepsis-induced brain dysfunction (SIBD). Sixty rats were randomly assigned into Sham group, SAE group (Model group), SAE + Sen I group (72 mg/kg, Sen I group), and SAE+ positive control group (RTA 402, Nrf2 receptor agonist, RTA 402 group), with 15 rats in each group. The cecal ligation and puncture (CLP) method was applied to induce sepsis in rats. SAE modeling was verified 6 h after operation. T

Reactive astrocyte-derived exosomes enhance intracranial lymphatic drainage in mice after intracranial hemorrhage.

BACKGROUND: After intracranial hemorrhage (ICH), the formation of primary hematoma foci leads to the development of secondary brain injury f … S: Hemin, an iron-rich porphyrin compound, was used to construct the in vitro model of ICH. Primary astrocytes were treated with complete medium supplemented with different concentrations of hemin to obtain exosomes secreted by them, and mice with ICH induced by the collagenase method were intervened by intranasal administration. Solute clearance efficiency …