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SARS-CoV-2 Infection Influences Wnt/β-Catenin Pathway Components in Astrocytes.

The mechanisms by which SARS-CoV-2 infection lead to neuroinflammation and cognitive impairment in COVID-19 and Long COVID are unclear. Cerebrovascular Wnt/β-catenin pathway activity is suppressed in association with neuroinflammation and cognitive impairment in a mouse model of COVID-19. In this study, we asked whether SARS-CoV-2 (NY Iota strain) infection of astrocytes would result in cell-autonomous changes in Wnt/β-catenin pathway components. We report that induced pluripotent stem cell (hiPSC)-derived human astrocytes (iAs) are susceptible to sustained infection with SARS-CoV-2 in vitro. …

Altered Ca2+ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes.

Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. Although several studies have highlighted cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy. We treated primary ce…

The restoration of REST inhibits reactivity of Down syndrome iPSC-derived astrocytes.

INTRODUCTION: Accumulating evidence indicates that the increased presence of astrocytes is fundamentally linked to the neurological dysfunctions observed in individuals with Down syndrome (DS). REST (RE1-silencing transcription factor), as a chromatin modifier, regulates 15,450 genes in humans. REST is a key regulatory element that governs astrocyte differentiation, development, and the maintenance of their physiological functions. The downregulation of REST may disrupt the homeostatic balance of astrocytes in DS. METHODS: This study aims to elucidate the role of REST in DS-astrocytes through…

Mechanism of miR-4465 targeting PTEN-mediated autophagy of astrocytes in epilepsy.

BACKGROUND: To investigate the mechanism of miR-4465 targeting PTEN-mediated autophagy of astrocytes in epilepsy. METHODS: Serum samples were collected from epileptic children and healthy children. Extract foreign bodies from serum samples and determine their quality. The exosomes were sequenced, and the abnormal expression of miRNA in patients' serum exosomes was analysed, and the expression of miR-4465 was verified by quantitative PCR. Bioinformatics predicts the size of miR-4465 and makes GO and KEGG analyses. HEK293 cells were cultured, and the relationship between miR-4465 and its target…

Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.

Astrocytes in the retina and optic nerve head play an important role in the pathogenesis of glaucoma. Astrocytes extensively express connexin 43 (Cx43), a protein that forms gap junction (GJ) channels and transmembrane unopposed hemichannels. While it is well documented that Cx43 expression is augmented in retinal injuries, the role of astrocytic Cx43 channels in glaucomatous injury is not fully understood. Here, we used a mouse model of ocular hypertension caused by intracameral microbead injections and a more severe model, optic nerve crush (ONC) injury, and assessed changes in Cx43 expressi…

Astrocytes-derived LCN2 triggers EV-A71-induced muscle soreness via accumulating lactate.

Viral muscle soreness (VMS) is a common feature during acute viral infections, including those caused by enteroviruses, and it substantially diminishes patients' quality of life. At present, we aim to establish the "brain-muscle" axis to explore the underlying mechanisms of VMS. We initially observed that diminished pain threshold occurred in enterovirus A71 (EV-A71)-infected C57BL/6J and AG6 mice. Subsequently, RNA sequencing data showed that lipocalin 2 (LCN2) was up-regulated during multiple viral infections, including EV-A71, Japanese encephalitis virus, vesicular stomatitis virus, and Wes

Functional characteristics, intercellular interactions and pathophysiological associations of astrocytes in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, and its incidence rate is increasing at an alarming rate. Astrocytes exhibit a complex array of functions that play a critical role in the pathogenesis and progression of PD. These multifaceted functions substantially influence disease development and exacerbation. Although numerous studies have investigated the role of astrocytes in PD, the interactions between astrocytes and other cellular or molecular factors during the course of neurological deterioration in PD have not been comprehensively characterized. The…

BATF2 является регулятором интерферона β, сигнализирующего в астроцитах во время нейроинфламмации.

Астроцитический интерферон (IFN) (IFN) (информация) связан с уменьшением нейроинфламмации; однако эффекторы вниз по течению, ответственные за регулирование этой защиты, неизвестны. Здесь мы идентифицируем удельный коэффициент транскрипции IFN, основной коэффициент транскрипции лейцина АТФ-подобный АТФ2, который играет ключевую роль в модулировании последствий ITFN, сигнализирующих в астроцитах. Последовательность иммунопреобразования Хроматина показала, что НИМФ2 связывает и предотвращает перевыражение регулятивных факторов IFN (IRF)1 и IRF1, таких как caspase-1. Мы также показываем, что мыши

Совпадение в аннотации оригинала
Astrocytic interferon (IFN)γ signaling is associated with reduced neuroinflammation; however, downstream effectors responsible for regulatin … scription factor (BATF)2, that plays a key role in modulating the consequences of IFNγ signaling in astrocytes. Chromatin immunoprecipitation sequencing revealed that BATF2 binds and prevents the overexpression of IFN regulatory factor (IRF)1 and IRF1 targets such as caspase-1. We also show that Batf2-/- mice exhibit exacerbated clinical disease severity in …

The janus face of astrocytes in multiple sclerosis: Balancing protection and pathology.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system (CNS), predominantly affecting young adults with a notable female predominance. While the pathogenesis of MS involves complex interactions between peripheral immune cells and CNS glia, astrocytes-the most abundant glial cells-play a dual role in disease progression. Traditionally classified into pro-inflammatory A1 and neuroprotective A2 phenotypes, recent single-cell and spatial transcriptomics reveal that human astrocytes exhibit a continuum of states be…

RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes.

The leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and their phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the LRRK2-regulated RAB GTPase in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brain through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes …

Mitochondrial iron deficiency triggers cytosolic iron overload in PKAN hiPS-derived astrocytes.

Disease models of neurodegeneration with brain iron accumulation (NBIA) offer the possibility to explore the relationship between iron dyshomeostasis and neurodegeneration. We analyzed hiPS-derived astrocytes from PANK2-associated neurodegeneration (PKAN), an NBIA disease characterized by progressive neurodegeneration and high iron accumulation in the globus pallidus. Previous data indicated that PKAN astrocytes exhibit alterations in iron metabolism, general impairment of constitutive endosomal trafficking, mitochondrial dysfunction and acquired neurotoxic features. Here, we performed a more …

SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration.

Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These SrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory.…

Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.

The regulation of energy in the brain has garnered substantial attention in recent years due to its significant implications in various diso … peration and is continuously supplied by fuel from the blood due to limited internal energy stores. Astrocytes, which interface with neurons and blood vessels, play a crucial role in coordinating the brain's metabolic activity, and their dysfunction can have detrimental effects on brain health. This review characterizes the major energy substrates (glucose, …

Dorsal hippocampal astrocytes mediate the development of heroin withdrawal-enhanced fear learning.

There is a significant co-occurrence of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms linking chronic opioid use, withdrawal, and the development of PTSD are poorly understood. Our previous research has shown that proinflammatory cytokines, expressed primarily by astrocytes in the dorsal hippocampus (DH), play a role in the development of heroin withdrawal-enhanced fear learning (HW-EFL), an animal model of PTSD-OUD comorbidity. Given the role of astrocytes in memory, fear learning, and opioid use, our exper…

A comprehensive exploration of astrocytes in migraine: a bibliometric and visual analysis.

BACKGROUND: Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology. METHO…

Modulation of SNARE-dependent exocytosis in astrocytes improves neuropathology in Huntington's disease.

Huntington's disease (HD) is a fatal, progressive neurodegenerative disorder. Prior studies revealed an increase in extracellular glutamate levels after evoking astrocytic SNARE-dependent exocytosis from cultured primary astrocytes from mutant huntingtin (mHTT)-expressing BACHD mice compared to control astrocytes, suggesting alterations in astrocytic SNARE-dependent exocytosis in HD. We used BACHD and dominant-negative (dn)SNARE mice to decrease SNARE-dependent exocytosis from astrocytes to determine whether reducing SNARE-dependent exocytosis from astrocytes could rescue neuropathological cha…

Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology.

BACKGROUND: Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer's disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate and adaptive peripheral immune effectors. We previously showed that regulatory T cells (Tregs) have a beneficial impact on disease progression in AD-like pathology, notably by modulating the microglial response associated with Aβ deposits in a mouse model of amyloid pathology. Besides microglia, reactive astrocytes also play a critical role in neuroinflammatory processes ass…

Reactive astrocytes promote proteostasis in Huntington's disease through the JAK2-STAT3 pathway.

Huntington's disease is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in Huntington's disease that involves morphological, molecular and functional changes. How reactive astrocytes contribute to Huntington's disease is still an open question, especially because their reactive state is poorly reproduced in experimental mouse models. Here, we show that the JAK2-STAT3 pathway, a central cascade controlli…

What do we know about astrocytes and the antidepressant effects of DBS?

Treatment-resistant depression (TRD) is a debilitating condition that affects millions of individuals worldwide. Deep brain stimulation (DBS) has been widely used with excellent outcomes in neurological disorders such as Parkinson's disease, tremor, and dystonia. More recently, DBS has been proposed as an adjuvant therapy for TRD. To date, the antidepressant efficacy of DBS is still controversial, and its mechanisms of action remain poorly understood. Astrocytes are the most abundant cells in the nervous system. Once believed to be a "supporting" element for neuronal function, astrocytes are n…

Astrocytes derived from neural progenitor cells are susceptible to Zika virus infection.

Zika virus (ZIKV) was first isolated in 1947. From its isolation until 2007, symptoms of ZIKV-caused disease were limited (e.g., fever, hives, and headache); however, during the epidemic in Brazil in 2014, ZIKV infection caused Guillain-Barré syndrome in adults and microcephaly in fetuses and infants of women infected during pregnancy. The neurovirulence of ZIKV has been studied using neural progenitor cells (NPCs), brain organoids, neurons, and astrocytes. NPCs and astrocytes appear to be the most susceptible cells of the Central Nervous System to ZIKV infection. In this work, we aimed to dev…