Glia最新文献

{"title":"Pathogenic Variants in HEPACAM Alter Protein Localization and Interactome in Astrocytes of the Developing Mouse Cortex","authors":"Robert W. Lewis,&nbsp;Breana C. Dogan,&nbsp;Amy L. Stanek,&nbsp;Elliot B. Evans,&nbsp;Madelyn G. Coble,&nbsp;Hayli E. Spence-Osorio,&nbsp;Karen L. G. Farizatto,&nbsp;Angie L. Mordant,&nbsp;C. Allie Mills,&nbsp;Laura E. Herring,&nbsp;Katherine T. Baldwin","doi":"10.1002/glia.70218","DOIUrl":"https://doi.org/10.1002/glia.70218","url":null,"abstract":"<p>Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly, white matter edema, seizures, and motor and cognitive decline. Approximately 25% of MLC patients carry <i>HEPACAM</i> pathogenic variants, many of which are dominant missense variants causing remitting MLC Type 2b. <i>HEPACAM</i> encodes hepatic and glial cell adhesion molecule (hepaCAM), also known as GlialCAM, an astrocyte-enriched transmembrane protein with important roles in astrocyte territory establishment, gap junction coupling, branching organization, synaptic function, and development of the gliovascular unit. The molecular mechanisms through which pathogenic variants in <i>HEPACAM</i> alter hepaCAM protein function in vivo and facilitate MLC pathogenesis during brain development remain largely unknown. Here, we used new viral tools and proximity-based proteomics to examine how three different dominant pathogenic variants alter hepaCAM subcellular localization and protein interactome in astrocytes of the developing mouse cortex. We found dramatic changes in hepaCAM distribution throughout the astrocyte, which were common to all mutants tested. We also observed significant changes in protein interactome between wild type and mutant hepaCAM, including decreased association with previously described hepaCAM-interacting proteins Connexin 43 and CLC-2. Moreover, we identified the epilepsy-associate potassium channel KCNQ2 as a novel hepaCAM interaction partner and found reduced association between KCNQ2 and pathogenic variants. Collectively, our data provide new insights into hepaCAM protein function in astrocytes during brain development, reveal altered protein dynamics of pathogenic variants, and provide a new resource to explore the molecular underpinnings of MLC pathogenesis.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 11","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk Between Oligodendrocyte Lineage Cells and CNS-Resident and Peripheral Immune Cells Governs Demyelination and Remyelination in Multiple Sclerosis","authors":"Joohyun Park,&nbsp;So Yeong Cheon,&nbsp;Fuzheng Guo","doi":"10.1002/glia.70211","DOIUrl":"https://doi.org/10.1002/glia.70211","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by immune-mediated attacks on myelin produced by oligodendrocytes (OLs). Oligodendrocyte precursor cells (OPCs) and mature OLs are CNS cell types essential for generating myelin sheath, which supports saltatory conduction and neuronal metabolic support. Although the roles of CNS resident cells (neurons, microglia, astrocytes) and peripheral immune cells in MS pathogenesis are well established, our understanding of how oligodendrocyte lineage cells (OLCs)—comprising OPCs and mature OLs—bidirectionally interact with these cell types to influence disease progression remains incomplete. Emerging evidence emphasizes the critical role of disease-associated OLCs in neuroimmune responses and their underlying signaling mechanisms. Therefore, elucidating how pathological environments shaped by CNS and peripheral cells influence OLC function may identify critical therapeutic targets for promoting remyelination and recovery in MS. This review synthesizes current knowledge of OLC biology in health and disease, with emphasis on complex intercellular interactions that determine demyelination, remyelination, and axonal integrity in MS.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Type-Specific Extracellular Vesicles in Mouse Brain: Proteomic Signatures Highlight Astrocytic GlialCAM Network and GPCR Enrichment","authors":"Alba M. Lucart-Sanchez,&nbsp;Edward Sellés-Climent,&nbsp;Jorge Navarro-Calvo,&nbsp;Guillem Pont-Espinós,&nbsp;Jose A. Gomez-Sanchez,&nbsp;Raúl Estévez,&nbsp;Luis M. Valor,&nbsp;Rocío Pérez-González","doi":"10.1002/glia.70212","DOIUrl":"https://doi.org/10.1002/glia.70212","url":null,"abstract":"<p>Extracellular vesicles (EVs) mediate intercellular communication in the central nervous system (CNS) and are emerging as biomarkers of brain health and disease. However, the molecular composition of cell type-specific brain EVs, particularly astrocyte-derived EVs (ADEVs), remains poorly defined. We performed comparative proteomic analysis of neuronal (NDEVs), microglial (MDEVs), and ADEVs from mouse brain using magnetic immunocapture and LC–MS/MS proteomic profiling. Each EV subtype displayed distinct molecular fingerprints. NDEVs were enriched in synaptic and neurogenesis-related proteins (e.g., APP, SNAP25, GPR158, and BDNF), whereas MDEVs contained immune and phagocytic markers (e.g., TMEM119, CX3CR1, CD11b). Strikingly, the ADEV proteome closely mirrored the recently characterized GlialCAM interactome from leukodystrophy research, encompassing GlialCAM/MLC1 and associated partners involved in ion and water homeostasis (EAAT1/2, AQP4, GJA1), together with GPCRs such as GPRC5B. This overlap suggests that ADEVs encapsulate a molecular scaffold characteristic of astrocytic endfeet, potentially extending their signaling functions to the extracellular space. In conclusion, our study provides a detailed comparative proteomic characterization of brain cell type-specific EVs, revealing that ADEVs contain the GlialCAM/MLC1 network and GPCRs. These findings identify candidate molecular signatures that support the future investigation of ADEVs for biomarker development and provide a proteomic framework for exploring their relationship with astrocytic endfoot biology, blood–brain barrier (BBB)-associated pathways, and neurodegenerative disorders.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk Between Oligodendrocyte Lineage Cells and CNS-Resident and Peripheral Immune Cells Governs Demyelination and Remyelination in Multiple Sclerosis","authors":"Joohyun Park,&nbsp;So Yeong Cheon,&nbsp;Fuzheng Guo","doi":"10.1002/glia.70211","DOIUrl":"https://doi.org/10.1002/glia.70211","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by immune-mediated attacks on myelin produced by oligodendrocytes (OLs). Oligodendrocyte precursor cells (OPCs) and mature OLs are CNS cell types essential for generating myelin sheath, which supports saltatory conduction and neuronal metabolic support. Although the roles of CNS resident cells (neurons, microglia, astrocytes) and peripheral immune cells in MS pathogenesis are well established, our understanding of how oligodendrocyte lineage cells (OLCs)—comprising OPCs and mature OLs—bidirectionally interact with these cell types to influence disease progression remains incomplete. Emerging evidence emphasizes the critical role of disease-associated OLCs in neuroimmune responses and their underlying signaling mechanisms. Therefore, elucidating how pathological environments shaped by CNS and peripheral cells influence OLC function may identify critical therapeutic targets for promoting remyelination and recovery in MS. This review synthesizes current knowledge of OLC biology in health and disease, with emphasis on complex intercellular interactions that determine demyelination, remyelination, and axonal integrity in MS.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Type-Specific Extracellular Vesicles in Mouse Brain: Proteomic Signatures Highlight Astrocytic GlialCAM Network and GPCR Enrichment","authors":"Alba M. Lucart-Sanchez,&nbsp;Edward Sellés-Climent,&nbsp;Jorge Navarro-Calvo,&nbsp;Guillem Pont-Espinós,&nbsp;Jose A. Gomez-Sanchez,&nbsp;Raúl Estévez,&nbsp;Luis M. Valor,&nbsp;Rocío Pérez-González","doi":"10.1002/glia.70212","DOIUrl":"https://doi.org/10.1002/glia.70212","url":null,"abstract":"<p>Extracellular vesicles (EVs) mediate intercellular communication in the central nervous system (CNS) and are emerging as biomarkers of brain health and disease. However, the molecular composition of cell type-specific brain EVs, particularly astrocyte-derived EVs (ADEVs), remains poorly defined. We performed comparative proteomic analysis of neuronal (NDEVs), microglial (MDEVs), and ADEVs from mouse brain using magnetic immunocapture and LC–MS/MS proteomic profiling. Each EV subtype displayed distinct molecular fingerprints. NDEVs were enriched in synaptic and neurogenesis-related proteins (e.g., APP, SNAP25, GPR158, and BDNF), whereas MDEVs contained immune and phagocytic markers (e.g., TMEM119, CX3CR1, CD11b). Strikingly, the ADEV proteome closely mirrored the recently characterized GlialCAM interactome from leukodystrophy research, encompassing GlialCAM/MLC1 and associated partners involved in ion and water homeostasis (EAAT1/2, AQP4, GJA1), together with GPCRs such as GPRC5B. This overlap suggests that ADEVs encapsulate a molecular scaffold characteristic of astrocytic endfeet, potentially extending their signaling functions to the extracellular space. In conclusion, our study provides a detailed comparative proteomic characterization of brain cell type-specific EVs, revealing that ADEVs contain the GlialCAM/MLC1 network and GPCRs. These findings identify candidate molecular signatures that support the future investigation of ADEVs for biomarker development and provide a proteomic framework for exploring their relationship with astrocytic endfoot biology, blood–brain barrier (BBB)-associated pathways, and neurodegenerative disorders.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frozen in Place: Proximity Labeling Maps Glial Interactomes Across Cell States","authors":"João Baltar,&nbsp;Rebecca Abati,&nbsp;Luísa Florido,&nbsp;Matthew G. Holt","doi":"10.1002/glia.70216","DOIUrl":"https://doi.org/10.1002/glia.70216","url":null,"abstract":"<p>Glial cells, including radial glia, oligodendrocyte precursor cells (OPCs), oligodendrocytes, astrocytes, and microglia, are active and dynamic regulators of central nervous system (CNS) development, homeostasis, and disease. Through extensive interactions with neurons, other glial populations, and the vasculature, they form highly specialized communication networks that are essential for normal brain function. While transcriptomic approaches have revealed extensive glial heterogeneity and enabled the prediction of putative signaling networks, a critical challenge remains in validating and translating these findings at the level of distinct protein complexes existing both within and between the various glial cell types. This is largely due to the fact that traditional proteomic technologies lack spatial resolution and/or fail to capture protein interaction networks. Proximity labeling (PL) has emerged as a powerful strategy to overcome these limitations by enabling cell-type-specific mapping of protein networks and subcellular proteomes, with spatial and temporal precision. Emerging studies have applied PL enzymes, such as BioID, TurboID, and HRP, across diverse glial populations, starting to uncover protein networks supporting their interactions with neurons and vascular elements, allowing metabolic support, maintenance of microenvironment homeostasis and cell–cell communication (including synaptic modulation). In this review, we summarize the main PL enzymes, discuss key studies across different glial cell types, and examine the technical challenges and future perspectives of applying PL to investigate glial biology. By complementing transcriptomic data with spatially resolved proteomic insights, PL provides a unique opportunity to deepen our understanding of glial cell biology in health and disease.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frozen in Place: Proximity Labeling Maps Glial Interactomes Across Cell States","authors":"João Baltar,&nbsp;Rebecca Abati,&nbsp;Luísa Florido,&nbsp;Matthew G. Holt","doi":"10.1002/glia.70216","DOIUrl":"https://doi.org/10.1002/glia.70216","url":null,"abstract":"<p>Glial cells, including radial glia, oligodendrocyte precursor cells (OPCs), oligodendrocytes, astrocytes, and microglia, are active and dynamic regulators of central nervous system (CNS) development, homeostasis, and disease. Through extensive interactions with neurons, other glial populations, and the vasculature, they form highly specialized communication networks that are essential for normal brain function. While transcriptomic approaches have revealed extensive glial heterogeneity and enabled the prediction of putative signaling networks, a critical challenge remains in validating and translating these findings at the level of distinct protein complexes existing both within and between the various glial cell types. This is largely due to the fact that traditional proteomic technologies lack spatial resolution and/or fail to capture protein interaction networks. Proximity labeling (PL) has emerged as a powerful strategy to overcome these limitations by enabling cell-type-specific mapping of protein networks and subcellular proteomes, with spatial and temporal precision. Emerging studies have applied PL enzymes, such as BioID, TurboID, and HRP, across diverse glial populations, starting to uncover protein networks supporting their interactions with neurons and vascular elements, allowing metabolic support, maintenance of microenvironment homeostasis and cell–cell communication (including synaptic modulation). In this review, we summarize the main PL enzymes, discuss key studies across different glial cell types, and examine the technical challenges and future perspectives of applying PL to investigate glial biology. By complementing transcriptomic data with spatially resolved proteomic insights, PL provides a unique opportunity to deepen our understanding of glial cell biology in health and disease.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Astrocyte Clock Controls Circadian Perineuronal Net Remodeling, Synapse Strength and Learning Behavior","authors":"Philip C. Smith,&nbsp;Elsa I. Quillin,&nbsp;Katheryn B. Lefton,&nbsp;Celia A. McKee,&nbsp;Brendan Dang,&nbsp;Thomas Papouin,&nbsp;Erik S. Musiek","doi":"10.1002/glia.70213","DOIUrl":"10.1002/glia.70213","url":null,"abstract":"<p>The circadian clock controls a vast array of cellular and organismal functions, from the molecular scale to behavior. While each cell is regimented by a cell-autonomous clock, few studies in the brain have dissected the circuit and behavioral contributions of cell-specific clocks. Relatedly, astrocytes are now known to play key roles in regulating synaptic function, circuit activity and behavior, but whether these functions are guided by astrocyte-autonomous clocks is unknown. Here, we report that post-natal deletion of the critical circadian clock gene <i>Bmal1</i> in astrocytes, which abrogates core clock function in a cell type specific manner, induced expression of genes related to extracellular matrix (ECM) production, maintenance, and remodeling. Circadian variations have been shown in a specific ECM structure, perineuronal nets (PNNs), which are implicated in synaptic function and plasticity. In astrocyte-specific <i>Bmal1</i> knockouts, hippocampal PNN abundance was decreased, and the circadian rhythm of these structures was also abolished. In line with evidence implicating PNNs, and the ECM in general, in synaptic function and plasticity, we found that astrocyte-specific <i>Bmal1</i> KO mice had increased synaptic strength but blunted long term potentiation (LTP), as well as impaired learning and memory performance in a novel object recognition task. Taken together, these findings suggest that the astrocyte circadian clock regulates circadian rhythms in perineuronal net abundance as well as synaptic plasticity and behavioral learning and memory.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CX3CR1 Modulates Migration of Resident Microglia Towards Cortical Laser-Induced Lesions","authors":"Jens Wagner,&nbsp;Henrike Antony,&nbsp;Cornelia Hoyer,&nbsp;Kristiina Lundgrén,&nbsp;Rabah Soliymani,&nbsp;Sophie Crux,&nbsp;Lena Justus,&nbsp;Kevin Keppler,&nbsp;Julia Steffen,&nbsp;Christian Kurts,&nbsp;Daniel R. Engel,&nbsp;Jochen Herms,&nbsp;Maciej Łałowski,&nbsp;Martin Fuhrmann","doi":"10.1002/glia.70207","DOIUrl":"https://doi.org/10.1002/glia.70207","url":null,"abstract":"<p>Microglia are innate immune cells of the central nervous system (CNS). They extend their processes and migrate toward injuries in vivo. However, how the fractalkine receptor (CX3CR1) influences microglial migration remains unknown. Label-free proteomic profiling predicted changes in Ras homology family (RHO)-signaling activity that hint at dysregulated cytoskeleton signaling in <i>Cx3cr1-</i>deficient murine cortex tissue. To further investigate microglial migration, we carried out two-photon in vivo imaging at 4-h intervals for 72 h after a laser lesion in the cortex. <i>Cx3cr1</i>-deficient microglia showed enhanced migration toward the lesion. Additionally, the length and velocity of microglial fine processes extending toward the lesion were increased in <i>Cx3cr1-</i>deficient microglia. Migration remained unchanged in <i>Ccr2</i>-deficient mice, indicating that monocyte-derived macrophages/microglia did not contribute to microglia accumulation around the lesion. These results demonstrate that CX3CR1 modulates microglia migration toward laser-induced CNS injury. Manipulating microglia migration via the CX3CR1 signaling axis is therefore a potential target for the treatment of CNS injury.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CX3CR1 Modulates Migration of Resident Microglia Towards Cortical Laser-Induced Lesions","authors":"Jens Wagner,&nbsp;Henrike Antony,&nbsp;Cornelia Hoyer,&nbsp;Kristiina Lundgrén,&nbsp;Rabah Soliymani,&nbsp;Sophie Crux,&nbsp;Lena Justus,&nbsp;Kevin Keppler,&nbsp;Julia Steffen,&nbsp;Christian Kurts,&nbsp;Daniel R. Engel,&nbsp;Jochen Herms,&nbsp;Maciej Łałowski,&nbsp;Martin Fuhrmann","doi":"10.1002/glia.70207","DOIUrl":"https://doi.org/10.1002/glia.70207","url":null,"abstract":"<p>Microglia are innate immune cells of the central nervous system (CNS). They extend their processes and migrate toward injuries in vivo. However, how the fractalkine receptor (CX3CR1) influences microglial migration remains unknown. Label-free proteomic profiling predicted changes in Ras homology family (RHO)-signaling activity that hint at dysregulated cytoskeleton signaling in <i>Cx3cr1-</i>deficient murine cortex tissue. To further investigate microglial migration, we carried out two-photon in vivo imaging at 4-h intervals for 72 h after a laser lesion in the cortex. <i>Cx3cr1</i>-deficient microglia showed enhanced migration toward the lesion. Additionally, the length and velocity of microglial fine processes extending toward the lesion were increased in <i>Cx3cr1-</i>deficient microglia. Migration remained unchanged in <i>Ccr2</i>-deficient mice, indicating that monocyte-derived macrophages/microglia did not contribute to microglia accumulation around the lesion. These results demonstrate that CX3CR1 modulates microglia migration toward laser-induced CNS injury. Manipulating microglia migration via the CX3CR1 signaling axis is therefore a potential target for the treatment of CNS injury.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}