Emerging roles of astrocytes as immune effectors in the central nervous system

Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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The role of astrocyte metabolic reprogramming in ischemic stroke (Review)

International Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: 55(3)

Published: Jan. 21, 2025

Ischemic stroke, a leading cause of disability and mortality worldwide, is characterized by the sudden loss blood flow in specific area brain. Intravenous thrombolysis with recombinant tissue plasminogen activator only approved pharmacological treatment for acute ischemic stroke; however, aforementioned has significant clinical limitations, thus there an urgent need development novel mechanisms therapeutic strategies stroke. Astrocytes, abundant versatile cells central nervous system, offer crucial support to neurons nutritionally, structurally physically. They also contribute blood‑brain barrier formation regulate neuronal extracellular ion concentrations. Accumulated evidence revealed involvement astrocytes regulation host neurotransmitter metabolism, immune response repair, different metabolic characteristics can process suggesting that targeted astrocyte reprogramming may prognosis In present review, current understanding multifaceted along its regulatory factors pathways, as well promote polarization balance, which hold promise immunometabolism‑targeted therapies were summarized.

Language: Английский

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Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(46)

Published: Nov. 5, 2024

The role of nonneuronal cells in the resolution cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial single-cell transcriptomic profiling male mouse brain during first week injury. Cortical gene expression was severely disrupted, defined by inflammation cell death lesion core, glial scar formation orchestrated multiple types on periphery. identified as a zone with intense cell–cell communication, prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each three major populations, an inflammatory-responsive state, resembling reactive states observed neurodegenerative contexts, observed. recovered spectrum ischemia-induced oligodendrocyte supports emerging hypothesis oligodendrocytes actively respond modulate neuroinflammatory stimulus. findings are further supported analysis other datasets from different models ischemic Collectively, present landmark dataset accompanied interactive visualization provides comprehensive view spatiotemporal organization postischemic brain.

Language: Английский

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Astrocyte heterogeneity in ischemic stroke: Molecular mechanisms and therapeutic targets

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106885 - 106885

Published: March 1, 2025

Language: Английский

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Transcriptional and neuroprotective effects of hexokinase-2 inhibitors administered after stroke

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

ABSTRACT The inflammatory response induced by stroke can exacerbate injury to peri-infarct tissue. Microglia and other immune cells that mediate this require increased glycolytic flux during pro-inflammatory activation. These cells, unlike neurons most cell types, utilize hexokinase-2 (HK2) rather than hexokinase-1 for glycolysis, such HK2 inhibitors may selectively target them suppress post-ischemic inflammation. Here we compared the effects of non-selective hexokinase inhibitor 2-deoxyglucose HK2-selective lonidamine 3-bromopyruvate on secondary after stroke. A spatial transcriptomic assessment was performed in parallel compare microglial gene expression microglia - neuron interactions screen off-target effects. Each suppressed upregulation attenuated stress functional pathways neighboring neurons, but had minimal effect neuronal uninjured cortex. were more effective suppressing morphological changes, oxidative stress, neurite loss. administered produced long-term improvements outcome. Selective thus provide a clinically applicable means activation thereby improve outcomes without endangering energy metabolism.

Language: Английский

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The Janus Face of Astrocytes in Multiple Sclerosis: Balancing Protection and Pathology

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111356 - 111356

Published: April 1, 2025

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system (CNS), predominantly affecting young adults with notable female predominance. While pathogenesis of MS involves complex interactions between peripheral immune cells CNS glia, astrocytes-the most abundant glial cells-play dual role disease progression. Traditionally classified into pro-inflammatory A1 neuroprotective A2 phenotypes, recent single-cell spatial transcriptomics reveal that human astrocytes exhibit continuum states beyond this binary paradigm. In MS, reactive contribute to neurotoxicity disrupting blood-brain barrier (BBB), promoting glutamate excitotoxicity, presenting antigens autoreactive T cells. Conversely, they also support repair through neurotrophic factor release (e.g., BDNF, CNTF) remyelination. Emerging therapies like dimethyl fumarate (DMF) fingolimod modulate astrocyte reactivity, targeting oxidative stress sphingosine-1-phosphate receptors mitigate neuroinflammation. However, challenges persist translating murine A1/A2 concepts as display heterogeneous, context-dependent responses influenced regional microenvironments stages. Advanced techniques, including multi-omics, highlight astrocyte-microglia crosstalk metabolic reprogramming key drivers pathology. This review synthesizes current evidence on heterogeneity, their Janus-faced roles therapeutic potential astrocyte-targeted strategies, advocating for precision approaches account human-specific biology. Future research must priorities human-centric biomarkers dynamic modelling bridge gap experimental findings clinical applications.

Language: Английский

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The laminar position, morphology, and gene expression profiles of cortical astrocytes are influenced by time of birth from ventricular/subventricular progenitors

Glia, Journal Year: 2024, Volume and Issue: 72(9), P. 1693 - 1706

Published: June 9, 2024

Astrocytes that reside in superficial (SL) and deep cortical layers have distinct molecular profiles morphologies, which may underlie specific functions. Here, we demonstrate the production of SL layer (DL) astrocyte populations from neural progenitor cells mouse is temporally regulated. Lineage tracking following utero postnatal electroporation with PiggyBac (PB) EGFP birth dating EdU FlashTag, showed apical progenitors produce astrocytes during late embryogenesis (E16.5) are biased to SL, while postnatally labeled (P0) DL. In contrast, born predominantly neurogenic window (E14.5) a random distribution Of interest, E13.5 dated at lower bias, FT labeling no bias. Finally, examination morphologies "biased" E16.5- P0-labeled demonstrated E16.5-labeled exhibit different layers, do not. Differences based on time also observed E16.5 versus astrocytes. Altogether, these results suggest morphological, molecular, positional diversity related their ventricular/subventricular zone progenitors.

Language: Английский

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Deciphering brain cellular and behavioral mechanisms: Insights from single‐cell and spatial RNA sequencing

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(4)

Published: July 1, 2024

The brain is a complex computing system composed of multitude interacting neurons. computational outputs this determine the behavior and perception every individual. Each cell expresses thousands genes that dictate cell's function physiological properties. Therefore, deciphering molecular expression each great significance for understanding its characteristics role in function. Additionally, positional information can provide crucial insights into their involvement local circuits. In review, we briefly overview principles single-cell RNA sequencing spatial transcriptomics, potential issues challenges data processing, applications research. We further outline several promising directions neuroscience could be integrated with sequencing, including neurodevelopment, identification novel microstructures, cognition behavior, neuronal positioning, molecules cells related to advanced functions, sleep-wake cycles/circadian rhythms, modeling believe deep integration these contribute significantly roles individual or types specific thereby making important contributions addressing critical questions those fields. This article categorized under: Evolution Genomics > Computational Analyses Disease Development Disease.

Language: Английский

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Digital Microfluidics for Sample Preparation in Low‐Input Proteomics

Small Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract Low‐input proteomics, also referred to as micro‐ or nanoproteomics, has become increasingly popular it allows one elucidate molecular processes in rare biological materials. A major prerequisite for the analytics of minute protein amounts, e.g., derived from low cell numbers, down single cells, is availability efficient sample preparation methods. Digital microfluidics (DMF), a technology allowing handling and manipulation liquid volumes, recently been shown be powerful versatile tool address challenges low‐input proteomics. Here, an overview provided on recent advances proteomics using DMF. In particular, capability DMF isolate proteomes cells small model organisms, perform all necessary chemical steps, such denaturation proteolytic digestion on‐chip, are highlighted. Additionally, prerequisites making these steps compatible with follow‐up analytical methods chromatography‐mass spectrometry will discussed.

Language: Английский

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Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges, and future perspectives on transcriptomic profiling

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Single-cell RNA sequencing (scRNA-seq) is a high-throughput transcriptomic approach with the power to identify rare cells, discover new cellular subclusters, and describe novel genes. scRNA-seq can simultaneously reveal dynamic shifts in phenotypes heterogeneities subtypes. Since publication of first protocol on 2009, this evolving technology has continued improve, through use cell-specific barcodes, adoption droplet-based systems, development advanced computational methods. Despite induction stress response during tissue dissociation process, remains popular technology, commercially available methods have been applied brain. Recent advances spatial transcriptomics now allow researcher capture positional context transcriptional activity, strengthening our knowledge organization cell-cell interactions spatially intact tissues. A combination data proteomic, metabolomic, or chromatin accessibility promising direction for future research. Herein, we provide an overview workflow, analyses methods, pros cons technology. We also summarize latest achievements stroke acute traumatic brain injury, applications transcriptomics.

Language: Английский

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