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Glutamine synthetase in astrocytes of the caudate and putamen is responsible for locomotor sensitization after nicotine exposure.

Glutamine synthetase (GS) in astrocytes regulates glutamatergic neurotransmission by maintaining glutamate clearance in the brain. This study determined that GS in astrocytes of the caudate and putamen (CPu) regulates locomotor sensitization after repeated nicotine exposure. Nicotine increased phosphorylated c-Jun N-terminal kinase (pJNK) by stimulating α7 nicotinic acetylcholine receptors in cultured glioma C6 cells and primary astrocytes in a Ca2+-dependent manner. Active JNK phosphorylated metabotropic glutamate receptor 1a (mGluR1a) at the carboxyl terminus of glutathione S-transferase-tag…

Refined qingkailing attenuates reactive astrocytes and glial scar formation after ischemia stroke via the EGFR/PLCγ pathway.

BACKGROUND: Ischemic stroke (IS) is the main cause of disability worldwide, and glial scar can impair neurological recovery during the post- … als. The treatments of oxygen and glucose deprivation/reoxygenation (OGD/R) were applied to primary astrocytes and an astrocyte-neuron co-culture model. RESULTS: RQKL was effective in improving neurological dysfunction, brain histopathologic manifestations, and reducing the degree of brain atrophy at different stages of glial scar. It also decreased the exp …

Oxidative stress-driven transcriptomic remodeling in human astrocytes reveals network signatures associated with neurodegenerative and cardiovascular processes.

Astrocytes are central to brain homeostasis, supporting neuronal metabolism, synaptic activity, and the blood-brain barrier. With aging, these glial cells undergo molecular and functional changes that weaken support functions and promote neuroinflammation, contributing to neurodegeneration. Yet the systems-level mechanisms by which astrocytes respond to aging-related stressors remain poorly defined in human models. Because aging also heightens risk for cardiovascular disease, cognitive impairment, type 2 diabetes, and systemic inflammation, clarifying shared astrocytic pathways is critical for…

Different roles of astrocytes in the blood-brain barrier during the acute and recovery phases of stroke.

Ischemic stroke, a frequently occurring form of stroke, is caused by obstruction of cerebral blood flow, which leads to ischemia, hypoxia, and necrosis of local brain tissue. After ischemic stroke, both astrocytes and the blood-brain barrier undergo morphological and functional transformations. However, the interplay between astrocytes and the blood-brain barrier has received less attention. This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood-brain barrier in ischemic stroke. Post-stroke, the structure of endoth…

Astrocytes from lamina cribrosa are involved in the autoregulatory function of optic nerve head vessels in vitro.

PURPOSE: To investigate the role of the lamina cribrosa (LC) astrocytes in the autoregulatory capacity of optic nerve head (ONH) vessels and to explore the underlying molecular mechanisms. METHODS: The Oxygen-glucose deprivation/reperfusion model (OGD/R) in vitro was constructed to examine the changes in cell morphology and protein expression in LC astrocytes. LC astrocytes were co-cultured with vascular smooth muscle cells (VSMCs) to detect the role of LC astrocytes in the autoregulatory function of vessels. RESULTS: The partial pressure of oxygen (PO2) in the supernatant of LC astrocytes w…

Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Transfer CD59 to Astrocytes to Alleviate Complement-Dependent Cytotoxicity.

The retinal astrocyte death induced by complement-dependent cytotoxicity (CDC) is the major etiology of retinal injury in patients with neur … Vs derived from SF-UCMSCs exerted a protective effect against CDC-mediated damage to murine retinal astrocytes, as evidenced by reduced formation of C5b-9 + membrane attack complexes and diminished astrocyte death. Mechanistically, this protective effect was associated with the transfer of CD59 from EVs to astrocytes. In summary, the establishment of this se …

Osteocalcin modulates hippocampal activities and influences glycophagy within astrocytes in a chronic unpredictable mild stress mouse model.

Osteocalcin (OCN), an active substance produced by bone tissue, has demonstrated potential in alleviating depressive symptoms and exerting e … ctional impacts of OCN in hippocampus using proteomic analysis. Additionally, the effects of OCN on astrocytes were investigated. Behavioral tests suggested that OCN significantly ameliorated the depressive - like behaviors of mice exposed to CUMS, manifesting by the reduced immobility time in the tail suspension test and forced swimming test. Results from t …

Combination therapy with 3-Hydroxybenzaldehyde and Albendazole modulates mitochondrial protein expression in astrocytes after Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongylus cantonensis is a zoonotic nematode that causes eosinophilic meningitis and central nervous system injury in huma … lecules, including glial fibrillary acidic protein, VDAC1, MCU, and cytochrome c. In cultured mouse astrocytes, soluble antigens from fifth-stage larval-activated astrocytes induced mitochondria-related molecule expression, but 3-HBA suppressed these effects. CONCLUSIONS/SIGNIFICANCE: These results suggest that the combination of 3-HBA and albendazole downr …

Пространственное профилирование белков показывает активную роль астроцитов в ядре хронического активного поражения во время множественного склероза.

Хронические активные повреждения являются проявлением множественного склероза (MS) и связаны с прогрессированием заболеваний. Хотя астроциты в значительной степени причастны к НР, мало что известно об их роли в повреждениях, особенно в ядре повреждения. В этой связи мы стремились получить представление о пространственной взаимосвязи между астроцитами и определенными районами хронических активных повреждений, а также лучше понять окружающую среду в относительно недостаточно изученном ядре повреждения, который состоит главным образом из астроцитов. Мы проанализировали четыре определенных белковы

Совпадение в аннотации оригинала
Chronic active lesions are a manifestation of multiple sclerosis (MS) and have been associated with disease progression. While astrocytes are heavily implicated in MS, little is known about their role in lesions, particularly in the lesion core. Here, we sought to gain insight into the spatial relationship between astrocytes and defined regions of chronic ac…

Reactive astrocytes promote tumor progression by up-regulating tumor protocadherin 1 expression in lung cancer brain metastasis.

Brain metastasis (BM) is one of the main causes of death in patients with non-small cell lung carcinoma. The specific pathological processes of BM, which are inextricably linked to the brain tumor microenvironment, such as the abundance of astrocytes, lead to limited treatment options and poor prognosis. Reactive astrocytes are acquired in the BM; however, the underlying mechanisms remain unclear. This study aimed to explore the mechanisms by which astrocytes promote BM development. We determined the crucial role of reactive astrocytes in promoting the proliferation and migration of brain meta…

Preparation of human astrocytes with potent therapeutic functions from human pluripotent stem cells using ventral midbrain patterning.

INTRODUCTION: Astrocytes are glial-type cells that protect neurons from toxic insults and support neuronal functions and metabolism in a healthy brain. Leveraging these physiological functions, transplantation of astrocytes or their derivatives has emerged as a potential therapeutic approach for neurodegenerative disorders. METHODS: To substantiate the clinical application of astrocyte-based therapy, we aimed to prepare human astrocytes with potent therapeutic capacities from human pluripotent stem cells (hPSCs). To that end, we used ventral midbrain patterning during the differentiation of h…

Mitochondrial dysfunction and increased reactive oxygen species production in MECP2 mutant astrocytes and their impact on neurons.

Studies on MECP2 function and its implications in Rett Syndrome (RTT) have traditionally centered on neurons. Here, using human embryonic stem cell (hESC) lines, we modeled MECP2 loss-of-function to explore its effects on astrocyte (AST) development and dysfunction in the brain. Ultrastructural analysis of RTT hESC-derived cerebral organoids revealed significantly smaller mitochondria compared to controls (CTRs), particularly pronounced in glia versus neurons. Employing a multiomics approach, we observed increased gene expression and accessibility of a subset of nuclear-encoded mitochondrial g

In vivo neural regeneration via AAV-NeuroD1 gene delivery to astrocytes in neonatal hypoxic-ischemic brain injury.

BACKGROUND: Neonatal hypoxic-ischemic brain injury (HIBI) is a significant contributor to neonatal mortality and long-term neurodevelopmenta … oxygen and 92% nitrogen for 90 min. Three days after the injury, NeuroD1 was delivered to reactive astrocytes of the injury site using the astrocyte-tropic adeno-associated viral (AAV) vector AAVShH19. AAVShH19 was engineered with the Cre-FLEX system for long-term tracking of infected cells. RESULTS: AAVShH19-mediated ectopic NeuroD1 expression effectively …

Baicalin and baicalein from Scutellaria baicalensis Georgi alleviate aberrant neuronal suppression mediated by GABA from reactive astrocytes.

AIMS: γ-aminobutyric acid (GABA) from reactive astrocytes is critical for the dysregulation of neuronal activity in various neuroinflammatory conditions. While Scutellaria baicalensis Georgi (S. baicalensis) is known for its efficacy in addressing neurological symptoms, its potential to reduce GABA synthesis in reactive astrocytes and the associated neuronal suppression remains unclear. This study focuses on the inhibitory action of monoamine oxidase B (MAO-B), the key enzyme for astrocytic GABA synthesis. METHODS: Using a lipopolysaccharide (LPS)-induced neuroinflammation mouse model, we con…

NHH promotes Sepsis-associated Encephalopathy with the expression of AQP4 in astrocytes through the gut-brain Axis.

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact ca … udies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammon …

Bystander activation of microglia by Brucella abortus-infected astrocytes induces neuronal death via IL-6 trans-signaling.

Inflammation plays a key role in the pathogenesis of neurobrucellosis where glial cell interactions are at the root of this pathological condition. In this study, we present evidence indicating that soluble factors secreted by Brucella abortus-infected astrocytes activate microglia to induce neuronal death. Culture supernatants (SN) from B. abortus-infected astrocytes induce the release of pro-inflammatory mediators and the increase of the microglial phagocytic capacity, which are two key features in the execution of live neurons by primary phagocytosis, a recently described mechanism whereby …

Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice.

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly ass … ed with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflamm …

Herpes simplex virus infection induces necroptosis of neurons and astrocytes in human fetal organotypic brain slice cultures.

BACKGROUND: Herpes simplex virus (HSV) encephalitis (HSE) is a serious and potentially life-threatening disease, affecting both adults and n … SC supported productive HSV-1 and HSV-2 infection, involving predominantly infection of neurons and astrocytes, leading to expression of pro-inflammatory cytokines and chemokines. Both viruses induced programmed cell death-especially necroptosis-in infected brain slices at later time points after infection. The virus spread, cell tropism and role of programm …

Cortical thickness alterations are associated with astrocytes and excitatory neuron-specific transcriptome signatures in pediatric bipolar disorder.

Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morpho … ome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptiona …

Modeling Cellular Crosstalk of Neuroinflammation Axis by Tri-cultures of iPSC-Derived Human Microglia, Astrocytes, and Neurons.

Neuroinflammation is a common early pathological feature in many neurodegenerative disorders, including Alzheimer's disease (AD), which has been heavily implicated as a causative factor in disease pathology. However, the role neuroinflammation and inflammatory cells, including microglia and astrocytes, play in AD development and progression has not been fully defined. To try to better understand and study this neuroinflammatory role in AD pathogenesis, researchers use a variety of model systems, particularly in vivo animal models. Despite their usefulness, these models do come with a variety o…