Microglia states and nomenclature: A field at its crossroads

Paolicelli, Rosa Chiara; Sierra, Amanda; Stevens, Beth; Tremblay, Marie‐Ève; Aguzzi, Adriano; Ajami, Bahareh; Amit, Ido; Audinat, Etienne; Bechmann, Ingo; Bennett, Mariko L.; Bennett, F. Chris; Bessis, Alain; Biber, Knut; Bilbo, Staci D.; Blurton‐Jones, Mathew; Boddeke, Erik; Brites, Dora; Brône, Bert; Brown, Guy C.; Butovsky, Oleg; Carson, Monica J.; Castellano, Bernardo; Colonna, Marco; Cowley, Sally A.; Cunningham, Colm; Davalos, Dimitrios; Jager, Philip L. De; Strooper, Bart De; Dénes, Ádám; Eggen, Bart J. L.; Eyo, Ukpong B.; Galea, Elena; Garel, Sonia; Ginhoux, Florent; Glass, Christopher K.; Gökçe, Özgün; Gómez-Nicola, Diego; González, Berta; Gordon, Siamon; Graeber, Manuel B.; Greenhalgh, Andrew D.; Gressèns, Pierre; Greter, Melanie; Gutmann, David H.; Haass, Christian; Heneka, Michael T.; Heppner, Frank L.; Hong, Soyon; Hume, David; Jung, Steffen; Kettenmann, Helmut; Kipnis, Jonathan; Koyama, Ryuta; Lemke, Greg; Lynch, Marina A.; Majewska, Ania K.; Malcangio, Marzia; Malm, Tarja; Mancuso, Renzo; Masuda, Takahiro; Matteoli, Michela; McColl, Barry W.; Miron, Véronique E.; Molofsky, Anna V.; Monje, Michelle; Mracskó, Éva; Nadjar, Agnès; Neher, Jonas J.; Neniskyte, Urte; Neumann, Harald; Нода, Мами; Peng, Bo; Peri, Francesca; Perry, V. Hugh; Popovich, Phillip G.; Pridans, Clare; Priller, Josef; Prinz, Marco; Ragozzino, Davide; Ransohoff, Richard M.; Salter, Michael W.; Schaefer, Anne; Schafer, Dorothy P.; Schwartz, Michal; Simons, Mikael; Smith, Cody J.; Streit, Wolfgang J.; Tay, Tuan Leng; Tsai, Li‐Huei; Verkhratsky, Alexei; Bernhardi, Rommy von; Wake, Hiroaki; Wittamer, Valérie; Wolf, Susanne; Wu, Long Jun; Wyss‐Coray, Tony

doi:10.1016/j.neuron.2022.10.020

Cited by 533 publications

(269 citation statements)

References 211 publications

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“…As shown in Figure 1 , mammalian microglia originate from primitive yolk sac progenitor cells [ 22 ]. During early embryonic development, microglia start invading the neuroepithelium at E8.5 in mice [ 23 ]. Microglia demonstrate an ameboid morphology during fetal brain development, which is important for their mobility and the phagocytosis of debris resulting from apoptosis and synaptic pruning.…”

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

“…In summary, mammalian microglia are yolk-sac-derived, long-lived cells within the CNS parenchyma that persist into adulthood and self-renew at a steady state. The identification of microglia is currently based on highly enriched genes expressed in microglia, also called “microglial markers”, which include transcription factors Pu.1; cytoplasmic markers such as ionized calcium-binding adapter molecule 1 (IBA1); and surface markers such as the purinergic receptor P2YR12, transmembrane protein 119 (TMEM119), and CSF1R [ 23 ].…”

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

“…In fact, microglia are cell populations with functional heterogeneity, and an age- and region-dependent gene expression signature. Their morphology, ultrastructure, and molecular profile are dynamic and plastic, resulting in the coexistence of many different cell states closely associated with their diverse functions [ 23 ]. Key modifying factors that lead to microglial heterogeneous states include age, sex, circadian time, local CNS signals, and peripheral cues, such as changes in the microbiota [ 32 ].…”

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

“…In addition, microglia play essential roles in regulating brain development and maintaining CNS homeostasis by participating in synapse remodeling, neurogenesis, neuronal function, angiogenesis, and myelination [ 33 , 34 ]. Surveillance, phagocytosis, and the capacity to release soluble factors are core properties through which microglia fulfil their important biological functions [ 23 ]. Microglial mobility (capability of moving around) and motility (capability of extending/retracting processes), determined by their microenvironment, are essential for their normal functions in both developing CNS and adult brain [ 28 ].…”

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

“…Microglia are keen responders and critical players in numerous disease conditions, responding to various challenges by changing their molecular profile, morphology, ultrastructure, as well as motility and function [ 23 ]. While microglia play a beneficial role in maintaining CNS homeostasis and regulating neuronal activity, synaptic plasticity, and cognitive function, they can also be detrimental in disease conditions or stages.…”

Section: Microglial Mechanisms Of Ad Pathogenesis and Memory Impairmentmentioning

confidence: 99%

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New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer’s Disease

Deng

et al. 2022

Biomolecules

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Alzheimer’s disease (AD) is the most common progressive and irreversible neurodegeneration characterized by the impairment of memory and cognition. Despite years of studies, no effective treatment and prevention strategies are available yet. Identifying new AD therapeutic targets is crucial for better elucidating the pathogenesis and establishing a valid treatment of AD. Growing evidence suggests that microglia play a critical role in AD. Microglia are resident macrophages in the central nervous system (CNS), and their core properties supporting main biological functions include surveillance, phagocytosis, and the release of soluble factors. Activated microglia not only directly mediate the central immune response, but also participate in the pathological changes of AD, including amyloid-beta (Aβ) aggregation, tau protein phosphorylation, synaptic dissection, neuron loss, memory function decline, etc. Based on these recent findings, we provide a new framework to summarize the role of microglia in AD memory impairment. This evidence suggests that microglia have the potential to become new targets for AD therapy.

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Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

Section: Origin and Physiological Function Of Microgliamentioning

confidence: 99%

Section: Microglial Mechanisms Of Ad Pathogenesis and Memory Impairmentmentioning

confidence: 99%

See 3 more Smart Citations

New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer’s Disease

Deng

et al. 2022

Biomolecules

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An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury

Walsh

Wychowaniec

Costello

et al. 2023

Adv Healthcare Materials

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Spinal cord injury (SCI) is a devastating condition with no curative therapy currently available. Immunomodulation can be applied as a therapeutic strategy to drive alternative immune cell activation and promote a proregenerative injury microenvironment. Locally injected hydrogels carrying immunotherapeutic cargo directly to injured tissue offer an encouraging treatment approach from an immunopharmacological perspective. Gelatin methacrylate (GelMA) hydrogels are promising in this regard, however, detailed analysis on the immunogenicity of GelMA in the specific context of the SCI microenvironment is lacking. Here, the immunogenicity of GelMA hydrogels formulated with a translationally relevant photoinitiator is analyzed in vitro and ex vivo. 3% (w/v) GelMA, synthesized from gelatin type‐A, is first identified as the optimal hydrogel formulation based on mechanical properties and cytocompatibility. Additionally, 3% GelMA‐A does not alter the expression profile of key polarization markers in BV2 microglia or RAW264.7 macrophages after 48 h. Finally, it is shown for the first time that 3% GelMA‐A can support the ex vivo culture of primary murine organotypic spinal cord slices for 14 days with no direct effect on glial fibrillary acidic protein (GFAP+) astrocyte or ionized calcium‐binding adaptor molecule 1 (Iba‐1+) microglia reactivity. This provides evidence that GelMA hydrogels can act as an immunotherapeutic hydrogel‐based platform for preclinical SCI.

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The Landscape of Biomimetic Nanovesicles in Brain Diseases

You,

Liang,

et al. 2023

Advanced Materials

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Brain diseases, such as brain tumors, neurodegenerative diseases, cerebrovascular diseases and brain injuries, are caused by various pathophysiological changes such as excessive or impaired angiogenesis, neuroinflammation, immune activation or suppression, neurodegenerative disorders, and neurovirulent protein deposition, which poses a serious health threat. Brain disorders are often difficult to treat due to the presence of the blood‐brain barrier (BBB), which hinders the delivery of drugs to the brain. Biomimetic nanovesicles (BNVs), including endogenous extracellular vesicles (EVs) derived from various cells and artificial nanovesicles (ANVs), possess the ability to penetrate the BBB and thus can be utilized for drug delivery to the brain. BNVs, especially endogenous EVs, are widely distributed in body fluids and usually carry various disease‐related signal molecules such as proteins, RNA and DNA, and may therefore also be analyzed to understand the etiology and pathogenesis of brain diseases. This review will cover the exhaustive classification and characterization of BNVs and pathophysiological roles involved in various brain diseases, and emphatically focus on nanotechnology‐integrated BNVs for brain disease theranostics, including various diagnosis strategies and precise therapeutic regulations (e.g., immunity regulation, disordered protein clearance, anti‐neuroinflammation, neuro‐regeneration, angiogenesis and the gut‐brain axis regulation). We also discuss and outline the remaining challenges and future perspectives regarding the nanotechnology‐integrated BNVs for the diagnosis and treatment of brain diseases.This article is protected by copyright. All rights reserved

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Microglia states and nomenclature: A field at its crossroads

Cited by 533 publications

References 211 publications

New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer’s Disease

New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer’s Disease

An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury

The Landscape of Biomimetic Nanovesicles in Brain Diseases

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