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Single-Cell RNA-Seq and Machine Learning Reveal Key Feature Genes of Astrocyte in Perioperative Neurocognitive Disorders.

Perioperative neurocognitive disorder (PND) is common in older patients after anesthesia and surgery, significantly increasing morbidity and mortality. However, the role of astrocytes in its pathogenesis remains limitedly understood. Here, we analyzed 9976 and 9484 single-cell transcriptomes from hippocampal cells of aged mice undergoing PND surgery or sham operation, focusing on astrocytes. We identified 13 distinct clusters corresponding to nine cell types, including astrocytes, microglia, neurons, oligodendrocytes, and other relevant cell populations. Specifically, five astrocyte subcluster…

Transcranial direct current stimulation alleviates chronic pain in knee osteoarthritis by modulating microglial and astrocytic polarization and neuroinflammation.

AIMS: Knee osteoarthritis (KOA) chronic pain is linked to neuroinflammation mediated by reactive astrocytes in the primary somatosensory cortex (S1). Reactive astrocytes are classified into neurotoxic A1 and neuroprotective A2 phenotypes, with activated microglia promoting A1 astrocyte formation during chronic pain progression. This study aimed to investigate whether transcranial direct current stimulation (tDCS) can alleviate KOA chronic pain by modulating glial phenotype conversion and neuroinflammatory processes. MAIN METHODS: Rats received an intra-articular injection of monosodium iodoac…

Astrocytic SIRT1 ameliorates cognitive deficits after traumatic brain injury via autophagy-mediated MEGF10 phagocytosis.

Traumatic brain injury (TBI) frequently causes cognitive dysfunction, with astrocytes playing a pivotal role in its pathogenesis. ​Specifically,​​ TBI triggers excessive astrocyte reactivity, ​leading to a phagocytic phenotype in astrocytes that contributes to abnormal synaptic phagocytosis and cognitive decline. ​Sirtuin 1 (SIRT1) reduction was region-specific, with significant downregulation observed in the hippocampus and cortex, reflecting the selective vulnerability of these regions to TBI-induced pathology. Although​ SIRT1 ​is​ a neuroprotective deacetylase, its regulatory mechanism in p…

Двойная целеопределённость тротуаров TLR9 и CGAS-STING Translates Attenuates Astrocyte Inflamitation: потенциальные последствия при множественном склерозе.

Цель этого исследования заключается в изучении роли 9-го рецептора Toll (TLR9), датчика деоксирибозы нуклеиновой кислоты (DNA), в активации астроцитов и его вклада в многочисленные патогенез склероза (MS). Кроме того, мы изучили, действуют ли TLR9 и циклический GMP-AMP синтазы-стимулятор интерфероновых генов (cGAS-STING) синергетически для содействия воспалительной активации астроцитов и дает ли комбинированное ингибирование обоих путей более высокий защитный эффект. Человеческие астроциты обрабатывались неметилированным цитосином-фосфоротиоатом-гуанином (CpG) олигододоксинуклеотидом при разли

Совпадение в аннотации оригинала
This study aims to investigate the role of Toll-like receptor 9 (TLR9), a deoxyribose nucleic acid (DNA) sensor, in astrocyte activation and … tivation and whether combined inhibition of both pathways offers superior protective effects. Human astrocytes were treated with unmethylated Cytosine-phosphorothioate-guanine (CpG) oligodeoxynucleotides at varying concentrations. Intervention groups included treatment with a TLR9 blocker (anti-TLR9) and a STING inhibitor (RU.521). Cellular responses were as …

Astrocytic-OTUD7B улучшает экспериментальный аутоиммунный энцефаломиелит путем стабилизации глиального фибрового кислотного белка и предотвращения воспаления.

Астроциты играют ключевую роль в патогенезе множественного склероза (МС); однако их регулирование в результате послетрансляционного погружения и дебицинации остается нерешенным. Это исследование показывает, что декубинирующий фермент OTUD7B в астроцитах защищает от аутоиммунного аутоэнцефаломиелита (EAE), модели MS, ограничивая нейроинфламмацию. RNA-последовательность изолированных астроцитов и пространственной транскриптомики показывает, что в EAE OTUD7B унифицирует хемакинское выражение в астроцитах подстрекательских повреждений, что связано с сокращением набора энцефалитогенных клеток CD4+T

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Astrocytes are central to the pathogenesis of multiple sclerosis (MS); however, their regulation by post-translational ubiquitination and deubiquitination is unresolved. This study shows that the deubiquitinating enzyme OTUD7B in astrocytes protects against murine experimental autoimmune encephalomyelitis (EAE), a model of MS, by limiting neuroinflammation. …

Электроакустация смягчает разрыв мозгового барьера и нейроинфламмацию через астроцитический MC4R в мышечной модели множественных склерозов.

Астроциты являются ключевыми регуляторами нейроинфламмации в множестве склерозов (МС). Электроакуптура (ЭА), которая является безопасной и эффективной с точки зрения затрат абсорбирующей терапией, продемонстрировала преимущества нейродегенеративных заболеваний, однако ее механизмы, связанные с астроцитами, остаются неясными. Здесь мы продемонстрировали, что EA в ST36 смягчает нарушение мозгового барьера (BBB) и нейроинфламмацию в период пикового периода экспериментального аутоиммунного энцефаломиелита (EAE). Кроме того, EA в ST36 отрегулировала выражение α-меланоцито-стимулирующего гормона (α-

Совпадение в аннотации оригинала
Astrocytes are key regulators of neuroinflammation in multiple sclerosis (MS). Electroacupuncture (EA), a safe and cost-effective adjuvant therapy, has shown benefits in neurodegenerative diseases, but its astrocyte-related mechanisms remain unclear. Here, we demonstrated that EA at ST36 alleviated blood-brain barrier (BBB) disruption and neuroinflammation d…

Астроцитовое исключение церулопласмина усугубляет окислительный стресс и демиелинацию в спинном мозге в муслиновой модели множественного склероза.

Астроцитический метаболизм железа имеет важное значение для поддержания гомеостаза центральной нервной системы (КНС), особенно в контексте нейродегенеративных и демиелинирующих расстройств, таких, как множественный склероз (МС). Разрушение этой системы регулирования может привести к накоплению железа, повышенному нейронному воспалению и обезвоживанию, что в конечном счете ускорит развитие болезни. Ceruloplasmin (Cp) — содержащий медь фермент ферросидазы, ярко выраженный астроцитами, играет ключевую роль в содействии эфффлюксу железа и детоксификации. Однако точный вклад астроцитического Cp в д

Совпадение в аннотации оригинала
Astrocytic iron metabolism is essential for maintaining central nervous system (CNS) homeostasis, particularly in the context of neurodegene … disease progression. Ceruloplasmin (Cp), a copper-containing ferroxidase enzyme highly expressed by astrocytes, plays a pivotal role in facilitating iron efflux and detoxification. However, the precise contribution of astrocytic Cp in demyelinating conditions is currently unknown. To investigate the role of astrocytic iron efflux and Cp in MS pathogenesis, w …

Longitudinal high-frequency blood biomarkers of axonal injury and astrocytic activation after immune reconstitution in multiple sclerosis.

BACKGROUND: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) reflect axonal damage and astrocytic injury. Their clinical role in longitudinal real-world monitoring after immune reconstitution therapy (IRT) in multiple sclerosis (MS) remains insufficiently defined. We evaluated longitudinal sNfL and sGFAP dynamics in people with multiple sclerosis (pwMS) treated with alemtuzumab (ATZ) as a model of IRT to determine their prognostic and monitoring value in real-world care. METHODS: PwMS initiating ATZ were prospectively followed up every three months for up to f

Inflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model.

Astrocyte secreted signals substantially affect disease pathology in neurodegenerative diseases. It remains little understood about how proinflammatory cytokines, such as interleukin-1α/tumor necrosis factor-α/C1q (ITC), often elevated in neurodegenerative diseases, alter astrocyte-secreted signals and their effects in disease pathogenesis. By selectively isolating astrocyte exosomes (A-Exo.) and employing cell type-specific exosome reporter mice, our current study showed that ITC cytokines significantly reduced A-Exo. secretion and decreased spreading of focally labeled A-Exo. in diseased SOD

Edaravone dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration.

Poststroke inflammation is essential in the mechanism of secondary injury, and it is orchestrated by resident microglia, astrocytes, and circulating immune cells. Edaravone dexborneol (EDB) is a combination of edaravone and borneol that has been identified as a clinical protectant for stroke management. In this study, we verified the anti-inflammatory effect of EDB in the mouse model of ischemia and investigated its modulatory action on inflammation-related cells. C57BL/6 male mice, which had the transient middle cerebral artery occlusion (tMCAO), were treated (i.p.) with EDB (15 mg/kg). EDB a…

Astrocyte-derived exosomal miR-378a-5p mitigates cerebral ischemic neuroinflammation by modulating NLRP3-mediated pyroptosis.

OBJECTIVE: This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia. METHODS: Astrocyte-derived exosomes were studied for treating cerebral ischemia in both in vitro and in vivo models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRT‒PCR. T

Protective roles of peroxiporins AQP0 and AQP11 in human astrocyte and neuronal cell lines in response to oxidative and inflammatory stressors.

In addition to aquaporin (AQP) classes AQP1, AQP4 and AQP9 known to be expressed in mammalian brain, our recent transcriptomic analyses identified AQP0 and AQP11 in human cortex and hippocampus at levels correlated with age and Alzheimer's disease (AD) status; however, protein localization remained unknown. Roles of AQP0 and AQP11 in transporting hydrogen peroxide (H2O2) in lens and kidney prompted our hypothesis that up-regulation in brain might similarly be protective. Established cell lines for astroglia (1321N1) and neurons (SHSY5Y, differentiated with retinoic acid) were used to monitor c

Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice.

Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elu … is early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent as …

Exosomes Derived from Meningitic Escherichia coli-Infected Brain Microvascular Endothelial Cells Facilitate Astrocyte Activation.

Numerous studies have shown that exosomes play a regulatory role in a variety of biological processes as well as in disease development and progression. However, exosome-mediated intercellular communication between brain microvascular endothelial cells (BMECs) and astrocytes during meningitic Escherichia coli (E. coli)-induced neuroinflammation remains largely unknown. Here, by using in vivo and in vitro models, we demonstrate that exosomes derived from meningitic E. coli-infected BMECs can activate the inflammatory response of astrocytes. A label-free quantitation approach coupled with LC-MS/…

Effect of curcumin-donepezil combination on spatial memory, astrocyte activation, and cholinesterase expressions in brain of scopolamine-treated rats.

BACKGROUND: The study investigated the effect of co-administration of curcumin and donepezil on several markers of cognitive function (such as spatial memory, astrocyte activation, cholinesterase expressions) in the brain cortex and hippocampus of scopolamine-treated rats. METHOD AND RESULTS: For seven consecutive days, a pre-treatment of curcumin (50 mg/kg) and/or donepezil (2.5 mg/kg) was administered. On the seventh day, scopolamine (1 mg/kg) was administered to elicit cognitive impairment, 30 min before memory test was conducted. This was followed by evaluating changes in spatial memory,

Sodium Butyrate Ameliorates Postoperative Delirium by Regulating Gut Microbiota Dysbiosis to Inhibit Astrocyte Activation in Aged Mice.

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, a…

Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabol … ild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo. LIMITATIONS: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether th …

Hypothermia promotes tunneling nanotube formation and the transfer of astrocytic mitochondria into oxygen-glucose deprivation/reoxygenation-injured neurons.

Mitochondrial transfer occurs between cells, and it is important for damaged cells to receive healthy mitochondria to maintain their normal function and protect against cell death. Accumulating evidence suggests that the functional mitochondria of astrocytes are released and transferred to oxygen-glucose deprivation/reoxygenation (OGD/R)-injured neurons. Mild hypothermia (33 °C) is capable of promoting this process, which partially restores the function of damaged neurons. However, the pathways and mechanisms by which mild hypothermia facilitates mitochondrial transfer remain unclear. We are c…

Botch improves cognitive impairment after cerebral ischemia associated with microglia-induced A1-type astrocyte activation.

Vascular cognitive impairment (VCI) is a clinical syndrome that arises from cerebrovascular issues and associated risk factors, resulting in … (TNF-α), and complement component 1q (C1q), leading to the activation of neurotoxic C3+ A1 reactive astrocytes. Then, the down-regulation of Botch exacerbated microglia-mediated inflammation, activated C3+ A1 astrocytes, worsened neuronal damage, and led to a decline in cognitive function. Conversely, the re-expression of Botch alleviated C3+ astrocyte activ …

NF-κB and JAK/STAT Signaling Pathways as Crucial Regulators of Neuroinflammation and Astrocyte Modulation in Spinal Cord Injury.

Spinal cord injury (SCI) leads to significant functional impairments below the level of the injury, and astrocytes play a crucial role in the pathophysiology of SCI. Astrocytes undergo changes and form a glial scar after SCI, which has traditionally been viewed as a barrier to axonal regeneration and functional recovery. Astrocytes activate intracellular signaling pathways, including nuclear factor κB (NF-κB) and Janus kinase-signal transducers and activators of transcription (JAK/STAT), in response to external stimuli. NF-κB and STAT3 are transcription factors that play a pivotal role in init…