Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 657 - 673

Published: Sept. 20, 2021

Language: Английский

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Microglia as hackers of the matrix: sculpting synapses and the extracellular space

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(11), P. 2472 - 2488

Published: Aug. 19, 2021

Abstract Microglia shape the synaptic environment in health and disease, but synapses do not exist a vacuum. Instead, pre- postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise four elements of contemporary tetrapartite synapse model. While research this area is still just beginning, accumulating evidence points toward novel role for microglia regulating ECM during normal brain homeostasis, such processes may, turn, become dysfunctional disease. As it relates to synapses, reported modify perisynaptic matrix, diffuse that surrounds dendritic axonal terminals, as well perineuronal nets (PNNs), specialized reticular formations compact enwrap neuronal subsets stabilize proximal synapses. The interconnected relationship between they embedded suggests alterations one structure necessarily affect dynamics other, may need sculpt within. Here, we provide an overview microglial regulation PNNs, propose candidate mechanisms these structures be modified, present implications modifications homeostasis

Language: Английский

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Oligodendrocyte precursor cells ingest axons in the mouse neocortex

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(48)

Published: Nov. 23, 2022

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by engulfment and degradation axonal branches synapses surrounding glial cells, including microglia astrocytes. However, small size phagocytic organelles complex, highly ramified morphology glia have made it difficult to define contribution these other cell types this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation reconstruct complete 3D morphologies distinct mouse visual cortex, providing unprecedented resolution composition. Unexpectedly, discovered that fine processes oligodendrocyte precursor cells (OPCs), a population abundant, dynamic progenitors, frequently surrounded axons. Numerous phagosomes phagolysosomes (PLs) containing fragments axons vesicular structures were present inside processes, suggesting OPCs engage axon pruning. Single-nucleus RNA sequencing from cortex revealed express key genes at stage, well neuronal transcripts, consistent active engulfment. Although are thought be responsible for majority synaptic pruning refinement, PLs ten times more abundant than markedly less newly generated oligodendrocytes, contribute substantially during cortical development.

Language: Английский

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Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: June 15, 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregation in the brain. Recent studies have revealed critical role of microglia AD pathogenesis. This review provides comprehensive summary current understanding microglial involvement AD, focusing on genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact synaptic plasticity neuronal regulation. Furthermore, recent developments drug discovery targeting are reviewed, highlighting potential avenues for therapeutic intervention. emphasizes essential insights into treatments.

Language: Английский

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The Role of Trogocytosis in the Modulation of Immune Cell Functions

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1255 - 1255

Published: May 19, 2021

Trogocytosis is an active process, in which one cell extracts the fragment from another cell, leading to transfer of surface molecules, together with membrane fragments. Recent reports have revealed that trogocytosis can modulate various biological responses, including adaptive and innate immune responses homeostatic responses. evolutionally conserved protozoan parasites eukaryotic cells. In some cases, results death, utilized as a mechanism for antibody-dependent cytotoxicity (ADCC). other trogocytosis-mediated intercellular protein leads both acquisition novel functions recipient cells loss cellular donor typically mediated by receptor–ligand interactions, TCR–MHC interactions Fcγ receptor-antibody-bound molecule interactions. Additionally, mediates MHC molecules non-immune cells, confers antigen-presenting activity on non-professional this review, we summarize recent advances our understanding role modulation.

Language: Английский

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Phagocytic astrocytes: Emerging from the shadows of microglia

Glia, Journal Year: 2022, Volume and Issue: 70(6), P. 1009 - 1026

Published: Feb. 10, 2022

Abstract Elimination of dead or live cells take place in both a healthy and diseased central nervous system (CNS). Dying are quickly cleared by phagocytosis for the maintenance CNS recovery after injury. Live parts thereof, such as synapses myelin, appropriately eliminated to maintain refine neural networks during development adulthood. Microglia, specific population resident macrophages CNS, classically considered primary phagocytes; however, astrocytes have also been highlighted phagocytes last decade. Phagocytic targets receptors reported be mostly common between microglia, which raises question how astrocytic differs from microglial phagocytosis, these two phagocytic systems cooperate. In this review, we address consequences particularly focusing on elusive points.

Language: Английский

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Oligodendrocyte precursor cells sculpt the visual system by regulating axonal remodeling

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(3), P. 280 - 284

Published: March 1, 2022

Abstract Many oligodendrocyte precursor cells (OPCs) do not differentiate to form myelin, suggesting additional roles of this cell population. The zebrafish optic tectum contains OPCs in regions devoid myelin. Elimination these impaired precise control retinal ganglion axon arbor size during formation and maturation retinotectal connectivity degraded functional processing visual stimuli. Therefore, fine-tune neural circuits independently their canonical role make

Language: Английский

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Microglia‐dependent remodeling of neuronal circuits

Journal of Neurochemistry, Journal Year: 2022, Volume and Issue: 163(2), P. 74 - 93

Published: Aug. 11, 2022

Microglia are tissue-resident macrophages responsible for the surveillance, neuronal support, and immune defense of brain parenchyma. Recently, role played by microglia in formation function circuits has garnered substantial attention. During development, have been shown to engulf precursors participate pruning mechanisms while, mature brain, they influence synaptic signaling, provide trophic support shape plasticity. studies unveiled different microglial characteristics associated with specific regions. This emerging view suggests that maturation distinct may be potentially molecular identity adopts across brain. Here, we review summarize known these cells thalamus, hippocampus, cortex, cerebellum. We focus on vivo highlight important remodeling relation neurodevelopmental neuropsychiatric disorders.

Language: Английский

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Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 6, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are risk factors attributed to AD. Though omics studies have helped identify pathways associated with AD, an integrated systems analysis available data could help understand mechanisms, potential biomarkers, therapeutic targets. Analysis transcriptomic sets from GEO database, proteomic metabolomic literature was performed deregulated commonality identified overlapping among sets. The included those neurotransmitter synapses, oxidative stress, inflammation, vitamins, complement, coagulation pathways. Cell type showed microglia, endothelial, myeloid, lymphoid cells affected. Microglia inflammation pruning synapses implications for memory cognition. protein-cofactor network B2, B6, pantothenate shows metabolic modulated these vitamins which overlap multi-omics analysis. Overall, molecular signature Treatment anti-oxidants, genetically susceptible individuals pre-symptomatic stage might better management disease.

Language: Английский

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Microglia-mediated synaptic pruning as a key deficit in neurodevelopmental disorders: Hype or hope?

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 79, P. 102674 - 102674

Published: Jan. 17, 2023

There is a consensus in the field that microglia play prominent role neurodevelopmental processes like synaptic pruning and neuronal network maturation. Thus, current momentum of associating deficits with disorders (NDDs) emerged. This concept challenged by rodent studies clinical data. Intriguingly, reduced numbers or altered microglial functions do not necessarily lead to overt NDD phenotypes, neuropsychiatric symptoms seem develop primarily adulthood. Hence, it remains open for discussion whether are truly indispensable healthy neurodevelopment. Here, we critically discuss highlight area- age dependency. We propose an updated model microglia-mediated context NDDs potential targeting treatment these disorders.

Language: Английский

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