Microglia as integrators of brain-associated molecular patterns

Trends in Immunology, Год журнала: 2024, Номер 45(5), С. 358 - 370

Опубликована: Апрель 23, 2024

Язык: Английский

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Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus

Nature Neuroscience, Год журнала: 2025, Номер 28(2), С. 268 - 279

Опубликована: Янв. 6, 2025

Язык: Английский

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Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution

Cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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The role of microglia in early neurodevelopment and the effects of maternal immune activation

Seminars in Immunopathology, Год журнала: 2024, Номер 46(1-2)

Опубликована: Июль 1, 2024

Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in offspring, particularly schizophrenia and autism spectrum disorder. Microglia, tissue-resident macrophages central nervous system, are implicated as potential mediators this risk. Early development, microglia start populating embryonic addition to their traditional role responders under homeostatic conditions, also intricately involved various early processes. The timing activation may interfere functioning neurodevelopment, potentially leading long-term consequences postnatal life. In review we will discuss involvement brain development prenatal stages life, while examining effects on Additionally, recent single cell RNA-sequencing studies focusing hypothesize how life microglial priming, through epigenetic reprogramming, be related disorders.

Язык: Английский

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Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore effects of both active and passive brain. We compare actively patients with nonimmunized neurologically healthy controls, identifying distinct microglial states associated clearance. Using high-resolution alongside single-cell RNA sequencing, delve deeper into transcriptional pathways involved removal after lecanemab treatment. uncover spatially responses that vary by region. Our analysis reveals upregulation triggering receptor expressed on myeloid cells 2 (TREM2) apolipoprotein E (APOE) microglia across approaches, which correlate positively antibody removal. Furthermore, show complement signaling contributes immunization. These findings provide new insights orchestrating shed light role immune-mediated Importantly, our work uncovers molecular targets could enhance Aβ-targeted immunotherapies, offering avenues for developing more effective therapeutic strategies combat AD.

Язык: Английский

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Microglia pack a toolbox for life

Trends in Immunology, Год журнала: 2024, Номер 45(5), С. 338 - 345

Опубликована: Апрель 13, 2024

Язык: Английский

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Spatiotemporal dynamics of the CD11c+ microglial population in the mouse brain and spinal cord from developmental to adult stages

Molecular Brain, Год журнала: 2024, Номер 17(1)

Опубликована: Май 18, 2024

Abstract CD11c-positive (CD11c + ) microglia have attracted considerable attention because of their potential implications in central nervous system (CNS) development, homeostasis, and disease. However, the spatiotemporal dynamics proportion CD11c individual CNS regions are poorly understood. Here, we investigated six (forebrain, olfactory bulb, diencephalon/midbrain, cerebellum, pons/medulla, spinal cord) from developmental to adult stages by flow cytometry immunohistochemical analyses using a reporter transgenic mouse line, Itgax-Venus . We found that total varied between during postnatal development. Specifically, was high bulb cerebellum at day P(4) P7, respectively, approximately half were The declined sharply all P14, low percentage persisted over P56. In cord, also P4 but increased again P21 thereafter. Interestingly, distribution pattern cord markedly changed gray matter white P21. Collectively, our findings reveal differences among early development normal mice. These improve understanding nature microglial heterogeneity its CNS.

Язык: Английский

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CD11c‐Expressing Microglia Are Transient, Driven by Interactions With Apoptotic Cells

Glia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 19, 2025

ABSTRACT Microglia, the parenchymal macrophage of central nervous system, serve crucial remodeling functions throughout development. Microglia are transcriptionally heterogenous, suggesting that distinct microglial states confer discrete roles. Currently, little is known about how dynamic these are, cues promote them, or they impact function. In developing retina, we previously found a significant proportion microglia express CD11c (Integrin αX, Itgax, subunit complement receptor 4) which has also been reported in other developmental and disease contexts. Here, sought to understand regulation function CD11c+ microglia. We track with prominent waves neuronal apoptosis postnatal retina. Using genetic fate mapping, provide evidence transition out state return homeostasis. show have elevated lysosomal content contribute clearance apoptotic neurons, acquisition expression partially dependent upon TAM AXL. selective ablation, not uniquely critical for phagocytic cells. Together, our data suggest transient induced by rather than specialized subset mediating elimination.

Язык: Английский

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Mechanisms and environmental factors shaping the ecosystem of brain macrophages

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 24, 2025

Brain macrophages encompass two major populations: microglia in the parenchyma and border-associated (BAMs) extra-parenchymal compartments. These cells play crucial roles maintaining brain homeostasis immune surveillance. Microglia BAMs are phenotypically epigenetically distinct exhibit highly specialized functions tailored to their environmental niches. Intriguingly, recent studies have shown that both originate from same myeloid progenitor during yolk sac hematopoiesis, but developmental fates diverge within brain. Several works partially unveiled mechanisms orchestrating development of mice humans; however, many questions remain unanswered. Defining molecular underpinnings controlling transcriptional epigenetic programs is one upcoming challenges for field. In this review, we outline current knowledge on ontogeny, phenotypic diversity, factors shaping ecosystem macrophages. We discuss insights garnered human studies, highlighting similarities differences compared mice. Lastly, address research gaps potential future directions Understanding how communicate with local environment tissue instructs trajectories functional features essential fully comprehend physiology disease.

Язык: Английский

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Activity-dependent regulation of microglia numbers by pyramidal cells during development shape cortical functions

Science Advances, Год журнала: 2025, Номер 11(8)

Опубликована: Фев. 19, 2025

Beyond their role as immune sentinels, microglia are actively involved in establishing and maintaining cortical circuits. Alteration microglial numbers has been associated with abnormal behaviors akin to those observed neurodevelopmental disorders. Consequently, the appropriate during development is crucial for ensuring normal function. Here, we uncovered a dynamic relationship between pyramidal cells that tunes through distinct phases of mouse postnatal development. Changes cell activity induce differential release activity-dependent proteins such Activin A, which, turn, adjusts accordingly. Decoupling this not only changes but long-term consequence on synaptic organizers, which ultimately affects Our findings reveal adapt critical time window development, consequently adjusting function demands developing local

Язык: Английский

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