Transcriptional and epigenetic decoding of the microglial aging process

Nature Aging, Journal Year: 2023, Volume and Issue: 3(10), P. 1288 - 1311

Published: Sept. 11, 2023

Abstract As important immune cells, microglia undergo a series of alterations during aging that increase the susceptibility to brain dysfunctions. However, longitudinal characteristics remain poorly understood. In this study, we mapped transcriptional and epigenetic profiles from 3- 24-month-old mice. We first discovered unexpected sex differences identified age-dependent (ADEM) genes process. then compared features reactivity in female at single-cell resolution level. To dissect functions aged excluding influence other established an accelerated microglial turnover model without directly affecting cells. By model, achieved aged-like non-aged brains confirmed per se contribute cognitive decline. Collectively, our work provides comprehensive resource for decoding process microglia, shedding light on how maintain functions.

Language: Английский

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Targeting pyroptosis with nanoparticles to alleviate neuroinflammatory for preventing secondary damage following traumatic brain injury

Science Advances, Journal Year: 2024, Volume and Issue: 10(2)

Published: Jan. 10, 2024

Posttraumatic neuroinflammation is a key driver of secondary injury after traumatic brain (TBI). Pyroptosis, proinflammatory form programmed cell death, considerably activates strong and amplifies the inflammatory response by releasing contents. Therefore, treatments targeting pyroptosis may have beneficial effects on treatment damage TBI. Here, cysteine-alanine-glutamine-lysine peptide-modified β-lactoglobulin (β-LG) nanoparticle was constructed to deliver disulfiram (DSF), C-β-LG/DSF, inhibit decrease neuroinflammation, thereby preventing TBI-induced injury. In post-TBI mice model, C-β-LG/DSF selectively targets injured brain, increases DSF accumulation, extends time systemic circulation DSF. can alleviate edema response, injury, promote learning, improve memory recovery in trauma. this study likely provided potential approach for reducing spread

Language: Английский

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Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 13, 2025

Lipid droplets (LDs), serving as the convergence point of energy metabolism and multiple signaling pathways, have garnered increasing attention in recent years. Different cell types within central nervous system (CNS) can regulate to generate or degrade LDs response diverse pathological stimuli. This article provides a comprehensive review on composition CNS, their generation degradation processes, interaction mechanisms with mitochondria, distribution among different types, roles played by these cells-particularly microglia astrocytes-in various prevalent neurological disorders. Additionally, we also emphasize paradoxical role post-cerebral ischemia inflammation explore potential underlying mechanisms, aiming identify novel therapeutic targets for this disease.

Language: Английский

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Mechanisms of astrocyte aging in reactivity and disease

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 21, 2025

Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor they contribute to neuronal dysfunction disease risk as organisms age. Here, we examine the transcriptional, cell biology, functional differences in across normal aging. Astrocytes at baseline heterogenous, responsive their environments, critical regulators of microenvironments function. With increasing age, adopt different immune-related senescence-associated states, which relate organelle loss homeostasis maintenance, both autonomously non-cell autonomously. These perturbed states increasingly associated with age-related onset neurodegeneration, suggesting that astrocyte a compelling target for future manipulation prevention disease.

Language: Английский

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Microglia–Astrocyte Interaction in Neural Development and Neural Pathogenesis

Cells, Journal Year: 2023, Volume and Issue: 12(15), P. 1942 - 1942

Published: July 27, 2023

The interaction between microglia and astrocytes exhibits a relatively balanced state in order to maintain homeostasis the healthy central nervous system (CNS). Disease stimuli alter microglia-astrocyte patterns elicit cell-type-specific responses, resulting their contribution various pathological processes. Here, we review similarities differences activation modes scenarios, encompassing different stages of neural development wide range disorders. aim is provide comprehensive understanding roles regeneration guiding new strategies for restoring CNS homeostasis.

Language: Английский

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Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 39(3), P. 491 - 502

Published: Jan. 3, 2023

Abstract As prominent immune cells in the central nervous system, microglia constantly monitor environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In diseased brain, crucial mediators of neuroinflammation that regulates a broad spectrum cellular responses. this review, we summarize current knowledge on multifunctional contributions to homeostasis their involvement neurodegeneration. We further comprehensive overview therapeutic interventions targeting neurodegenerative diseases. Notably, propose microglial depletion subsequent repopulation as promising replacement therapy. Although therapy is still its infancy, it will likely be trend development treatments diseases due versatility selectivity.

Language: Английский

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Brain-on-a-chip: an emerging platform for studying the nanotechnology-biology interface for neurodegenerative disorders

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 18, 2024

Language: Английский

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Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson’s disease model triggered by α-synuclein overexpression

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 9, 2025

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss mice via rAAV-hSYN injection cause neuronal expression α-synuclein, which produced behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior injection, maintaining it 8 eliminate microglia. This chronic treatment paradigm prevented development motor deficits concomitantly preserved cell weakened α-synuclein phosphorylation. Gene profiles related extracellular matrix (ECM) remodeling were increased after microglia depletion PD mice, further validated on protein level. demonstrated that exert adverse effects during α-synuclein-overexpression-induced lesion formation, their remodels ECM aids recovery following insult.

Language: Английский

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Microglia promote remyelination independent of their role in clearing myelin debris

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113574 - 113574

Published: Dec. 1, 2023

Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss. While therapies exist to slow MS progression, no treatment currently exists for remyelination. Remyelination, linked reduced disability in MS, relies on microglia and monocyte-derived macrophages (MDMs). This study aims understand the role of during remyelination lineage tracing depleting them. Microglial reveals that both MDMs initially accumulate, but later dominate lesion. Microglia engulf equal amounts inhibitory debris, after microglial depletion, compensate engulfing more debris. depletion does, however, reduce recruitment proliferation oligodendrocyte progenitor cells (OPCs) impairs their subsequent differentiation These findings underscore essential offer insights enhancing this process understanding regulation

Language: Английский

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LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 29, 2023

Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency degradation glia have remained largely unexplored. Here we show that LC3-associated phagocytosis (LAP), an pathway assisted by certain autophagy factors, promotes glial phagosome maturation Drosophila wing nerve. A LAP-specific subset autophagy-related genes is required for axon clearance, encoding members Atg8a (LC3) conjugation Vps34 lipid kinase complex including UVRAG Rubicon. Phagosomal Rubicon Atg16 WD40 domain-dependent mediate proper breakdown internalized fragments, overexpression accelerates elimination. Finally, LAP survival following traumatic brain injury. Our results reveal a role clearance neuronal vivo, with potential implications recovery injured system.

Language: Английский

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