Glia最新文献

{"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}

{"title":"GPR30 Functions as a Shared Inhibitory Signal for Both Pericyte-Mediated Angiogenesis and Oligodendrocyte Myelination","authors":"Si-Wen Hui,&nbsp;Xing Gao,&nbsp;Bin Yu,&nbsp;Qi-Jing Lei,&nbsp;Zhi-Yu Liu,&nbsp;Shuang-Ling Wu,&nbsp;Yong-Jie Cheng,&nbsp;Tao Chen,&nbsp;Lan Xiao,&nbsp;Tao Li,&nbsp;Feng Mei,&nbsp;Hong Ren,&nbsp;Fei Wang","doi":"10.1002/glia.70206","DOIUrl":"10.1002/glia.70206","url":null,"abstract":"<div>\u0000 \u0000 <p>Myelinogenesis is insufficient in numerous myelin-related diseases in the CNS, leading to functional impairments. Myelinogenesis couples with angiogenesis to ensure adequate need of oxygen and nutrients for oligodendrocyte (OL) differentiation. However, approaches to synchronize myelino-vascular coupling remain unavailable. We hypothesize the identification of shared signaling pathways in vascular cells and oligodendroglia may yield novel strategies to promote myelin repair through strengthening the blood vessel-myelination coupling. Here, single-cell sequencing and in situ hybridization revealed high expression of G-protein-coupled receptor 30 (<i>Gpr30</i>) in both vascular cells and oligodendroglia, with selective enrichment in pericytes and oligodendrocyte precursor cells (OPCs). Cell-specific deletion of GPR30 in pericytes driven by PDGFRβ^CreERT2 resulted in enhanced angiogenesis and myelination in developing brains. GPR30 deletion in OPCs or antagonizing GPR30 by G15 resulted in increased MBP-positive cell density and enhanced nanofiber wrapping capacity in vitro, thereby demonstrating an inhibiting role of GPR30 on OPC differentiation. To elucidate the coordinative role of GPR30 in both cell types, we employed NG2^CreERT to induce a conditional knockout of GPR30 in both NG2-positive pericytes and OPCs. The conditional deletion of GPR30 enhanced myelination and increased vascular density in developing brains. Further, GPR30 cKO or G15 treatment enhanced myelin repair and functional recovery in the chronic neonatal hypoxia and lysolecithin-induced demyelination model, suggesting that antagonizing GPR30 is a promising strategy to synchronize angiogenesis with myelination to promote myelinogenesis. These findings establish GPR30 antagonism as a promising approach to enhance myelin repair through synchronizing pericyte-mediated angiogenesis and OPC differentiation.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710641","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":"Enhancing Oligodendrogenesis Rescues Chronic Stress-Induced Behavioral Disorders Involving Neuronal and Synaptic Reorganization","authors":"Yu-Peng Dai,&nbsp;Can-Ling Xu,&nbsp;Hao Luo,&nbsp;Zhi-Yu Liu,&nbsp;Guo-Xiao Meng,&nbsp;Jia-Lin Li,&nbsp;An-Cheng Yu,&nbsp;Xin Chen,&nbsp;Xing Gao,&nbsp;Xi Zhang,&nbsp;Jia-Li Wang,&nbsp;Tao Chen,&nbsp;Lan Xiao,&nbsp;Fei Wang,&nbsp;Feng Mei,&nbsp;Qi-Jing Lei,&nbsp;Tao Li","doi":"10.1002/glia.70217","DOIUrl":"10.1002/glia.70217","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic stress induces psychiatric disorders, including depression and anxiety, yet effective therapies remain limited. Myelin in adult brains undergoes dynamic remodeling through oligodendrocyte precursor cells (OPCs) differentiation into oligodendrocytes (OLs) and the degeneration of pre-existing myelin. However, how chronic stress alters myelin dynamics and whether this represents a therapeutic target remains unclear. Here, adult mice subjected to 4-h daily restraint for 2 weeks exhibited significant anxiety, depression, and social deficits. Histological examinations revealed reduced OPC and OL density, decreased c-Fos-positive neurons, and loss of synaptic proteins in the brains exposed to chronic stress. To understand the dynamic changes of myelin, cell-lineage labeling and tracing demonstrated that chronic stress exposure remarkably inhibited oligodendrogenesis in the medial prefrontal cortex (mPFC), motor cortex, hippocampus, and amygdala, as revealed by the NG2^CreERT; Tau-mGFP line, but did not significantly change pre-existing myelin as revealed by a newly generated line for mature OLs and myelin. To explore the role of myelinogenesis changes, adult myelin formation was inhibited by Olig2 conditional knockout in OPCs, resulting in decreased neuronal synaptic proteins and activity, accompanied by anxiety and depressive-like behaviors. Conversely, enhancing myelinogenesis through conditional deletion of the M1R in OPCs of stressed mice resulted in higher number of c-Fos-positive neurons, elevated synaptic protein expression, and a partial reversal of the behavioral deficits. Importantly, treating the stressed animal with the pro-myelination drug clemastine phenocopied the effects of M1R deletion on histological and behavioral disorders. Together, our findings demonstrate that enhancing oligodendrogenesis represents a promising strategy to rescue CRS-caused behavioral disorders.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704723","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":"In Transected Nerves, Distal Repair Schwann Cells at the Injury Site Direct and Accelerate Axonal Regrowth","authors":"Daniel E. Lysko,&nbsp;Annika R. Johnson,&nbsp;William S. Talbot","doi":"10.1002/glia.70214","DOIUrl":"10.1002/glia.70214","url":null,"abstract":"<p>In vertebrate peripheral nerves, damaged axons can regrow after injury, but the outcomes of regeneration are variable and often incomplete. Schwann cells in injured nerves are important for repair, but their actions at different positions and stages of nerve repair are not well understood. We have investigated the roles of Schwann cells in a larval zebrafish nerve injury model, in which nerves are visible in living animals during development, the initial injury response, and regrowth of transected axons. After mechanical injury, distal Schwann cells adopted a repair phenotype characterized by changes in gene expression, elongation, and ability to guide axons across the injury site. In contrast, proximal Schwann cells associated with axons that regrew along aberrant paths at the injury site. In <i>erbb2</i> mutants with greatly decreased Schwann cells, developmental axon growth was normal, but axonal regrowth after transection was greatly slowed and often misdirected. By examining animals with nerves partially populated by Schwann cells, we found that axons could regrow through regions devoid of Schwann cells, provided that at least one distal Schwann cell was at the injury site. Timelapse imaging revealed that distal Schwann cells contacted axons, which then regrew along the correct path. In <i>irf8</i> mutants with greatly decreased macrophages, debris from transected axons was cleared on schedule, and axonal regrowth was normal. Our studies demonstrate that Schwann cells immediately distal to the injury site have a unique and essential role in axonal regrowth.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688154","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":"Gq Signaling in Microglia Triggers Interferon Responses and Improves Outcome After Ischemic Stroke","authors":"Lynn Bitar,&nbsp;Marie-Luise Brehme,&nbsp;Charlotte Oldenburg,&nbsp;Sara Isla Cainzos,&nbsp;Michael G. Kaul,&nbsp;Tobias Mummert,&nbsp;Malte Borggrewe,&nbsp;Thomas G. Oertner,&nbsp;Tim Magnus","doi":"10.1002/glia.70209","DOIUrl":"10.1002/glia.70209","url":null,"abstract":"<p>Post-stroke recovery remains limited despite advances in acute reperfusion therapies, underscoring the need to better understand underlying mechanisms that shape repair. Microglia, the resident immune cells of the central nervous system, orchestrate responses to ischemic injury and critically influence neurovascular remodeling, axonal reorganization, and functional recovery. Emerging evidence indicates that inflammatory preconditioning can reprogram microglial responses to subsequent insults, yet the exact intracellular signaling pathways mediating this adaptive state remain incompletely defined. Here, we used a chemogenetic approach to selectively activate Gq signaling in microglia employing a microglia-specific DREADD mouse model. This strategy mimics Gq-coupled receptor activation in microglia in the absence of peripheral immune engagement. Pre-ischemic Gq activation significantly reduced infarct sizes at 24 h after experimental stroke in female mice and at 7 days in both sexes. Morphological analyses revealed that Gq-conditioned microglia exhibited increased structural complexity, adopting a highly ramified, spatially compact phenotype and higher CD68 expression, indicating increased phagocytic activity. Transcriptional profiling demonstrated that Gq activation primes autophagy-related defense pathways in microglia, resulting in upregulation of interferon-stimulated genes 7 days after stroke in both sexes. Together, our findings identify Gq signaling as a key modulatory pathway capable of reprogramming microglial phenotype and enhancing stroke recovery. These results highlight the plasticity of microglial signaling networks and support targeted modulation of microglial Gq pathways.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688149","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":"Müller Glia–Vasculature Interactions in the Developing Retina","authors":"Samira Monshietehadi,&nbsp;Angel J. Garcia,&nbsp;Benjamin E. Smith,&nbsp;Matthew Tarchick,&nbsp;Kiara Abhayaratne,&nbsp;Aileen Conley,&nbsp;Marla B. Feller","doi":"10.1002/glia.70204","DOIUrl":"https://doi.org/10.1002/glia.70204","url":null,"abstract":"<p>Coordinated signaling among neurons, glia, and the vasculature is essential for nervous system development. In the developing retina, spontaneous cholinergic retinal waves are the primary source of neural activity during the early maturation of the vasculature. Here, we test the hypothesis that retinal waves influence angiogenesis and the maturation of the glial–vascular interface. We first found that retinal vasculature grew normally in mice lacking β2-containing nicotinic acetylcholine receptor–mediated retinal waves, demonstrating that early spontaneous activity is not required for angiogenesis. We next examined how Müller glia establish and signal at the developing glial–vascular interface. Sparse labeling and immunohistochemistry revealed that Müller glial lateral processes closely associate with endothelial tip cells during intermediate and deep layer angiogenesis and establish Aquaporin-4–enriched endfeet at vascular contact sites from the earliest stages of vascular growth. These associations were stable across development and persisted even when diving-vessel trajectories were disrupted in Piezo2 conditional knockouts. To determine whether glial signaling at the vascular interface is coupled to retinal waves, we combined two-photon calcium imaging with simultaneous retinal ganglion cell voltage-clamp recordings. Müller glial endfeet exhibited robust, compartmentalized calcium transients that were largely uncorrelated with retinal waves. Although blocking GABA-A receptors with gabazine increased wave-correlated activity in all glial compartments, the majority of endfoot calcium signaling remained wave-independent. Together, these findings support a model in which both angiogenesis and establishment of the Müller glial–vascular interface proceed through wave-independent developmental programs.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667442","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":"Müller Glia–Vasculature Interactions in the Developing Retina","authors":"Samira Monshietehadi,&nbsp;Angel J. Garcia,&nbsp;Benjamin E. Smith,&nbsp;Matthew Tarchick,&nbsp;Kiara Abhayaratne,&nbsp;Aileen Conley,&nbsp;Marla B. Feller","doi":"10.1002/glia.70204","DOIUrl":"https://doi.org/10.1002/glia.70204","url":null,"abstract":"<p>Coordinated signaling among neurons, glia, and the vasculature is essential for nervous system development. In the developing retina, spontaneous cholinergic retinal waves are the primary source of neural activity during the early maturation of the vasculature. Here, we test the hypothesis that retinal waves influence angiogenesis and the maturation of the glial–vascular interface. We first found that retinal vasculature grew normally in mice lacking β2-containing nicotinic acetylcholine receptor–mediated retinal waves, demonstrating that early spontaneous activity is not required for angiogenesis. We next examined how Müller glia establish and signal at the developing glial–vascular interface. Sparse labeling and immunohistochemistry revealed that Müller glial lateral processes closely associate with endothelial tip cells during intermediate and deep layer angiogenesis and establish Aquaporin-4–enriched endfeet at vascular contact sites from the earliest stages of vascular growth. These associations were stable across development and persisted even when diving-vessel trajectories were disrupted in Piezo2 conditional knockouts. To determine whether glial signaling at the vascular interface is coupled to retinal waves, we combined two-photon calcium imaging with simultaneous retinal ganglion cell voltage-clamp recordings. Müller glial endfeet exhibited robust, compartmentalized calcium transients that were largely uncorrelated with retinal waves. Although blocking GABA-A receptors with gabazine increased wave-correlated activity in all glial compartments, the majority of endfoot calcium signaling remained wave-independent. Together, these findings support a model in which both angiogenesis and establishment of the Müller glial–vascular interface proceed through wave-independent developmental programs.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667440","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":"Predicting Relevant Microglia-Associated Cell–Cell Communication Pathways in Alzheimer's Disease: A Role for SPP1","authors":"Janssen M. Kotah,&nbsp;Marina Trombetta Lima,&nbsp;Esmée C. Dragt,&nbsp;Asimenia Voulgaroglou,&nbsp;Nieske Brouwer,&nbsp;Inge R. Holtman,&nbsp;Susanne M. Kooistra,&nbsp;Bart J. L. Eggen","doi":"10.1002/glia.70210","DOIUrl":"https://doi.org/10.1002/glia.70210","url":null,"abstract":"<p>Microglia play a key role in the pathophysiology of Alzheimer's Disease (AD) and their increased heterogeneity likely affects disease progression. We previously identified distinct microglial signatures that were enriched in AD donors and associated with amyloid and tau, respectively. Here we generated a snRNAseq dataset from postmortem control and AD cases and analyzed alterations in cell–cell communication pathways that might be relevant to AD pathophysiology. One signaling pathway perturbed in AD cases involved <i>SPP1</i>, and while this pathway was also present in control samples, microglia–microglia SPP1 signaling was restricted to AD donors. Further analyses within microglia–microglia signaling predict AD-specific induction of <i>GAS6-AXL</i> signaling (from inflammatory and ribosomal microglia), and <i>SPP1-ITGAV/ITGB5</i> signaling (from disease-associated and inflammatory microglia, among others). Together, these findings might in part explain the increased microglia phagocytic profile described in AD. RNAscope confirmed enrichment of <i>SPP1</i> expressing microglia near amyloid plaques in AD brain tissue samples. These data indicate altered cellular communications between microglia in the AD brain.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667439","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":"Predicting Relevant Microglia-Associated Cell–Cell Communication Pathways in Alzheimer's Disease: A Role for SPP1","authors":"Janssen M. Kotah,&nbsp;Marina Trombetta Lima,&nbsp;Esmée C. Dragt,&nbsp;Asimenia Voulgaroglou,&nbsp;Nieske Brouwer,&nbsp;Inge R. Holtman,&nbsp;Susanne M. Kooistra,&nbsp;Bart J. L. Eggen","doi":"10.1002/glia.70210","DOIUrl":"https://doi.org/10.1002/glia.70210","url":null,"abstract":"<p>Microglia play a key role in the pathophysiology of Alzheimer's Disease (AD) and their increased heterogeneity likely affects disease progression. We previously identified distinct microglial signatures that were enriched in AD donors and associated with amyloid and tau, respectively. Here we generated a snRNAseq dataset from postmortem control and AD cases and analyzed alterations in cell–cell communication pathways that might be relevant to AD pathophysiology. One signaling pathway perturbed in AD cases involved <i>SPP1</i>, and while this pathway was also present in control samples, microglia–microglia SPP1 signaling was restricted to AD donors. Further analyses within microglia–microglia signaling predict AD-specific induction of <i>GAS6-AXL</i> signaling (from inflammatory and ribosomal microglia), and <i>SPP1-ITGAV/ITGB5</i> signaling (from disease-associated and inflammatory microglia, among others). Together, these findings might in part explain the increased microglia phagocytic profile described in AD. RNAscope confirmed enrichment of <i>SPP1</i> expressing microglia near amyloid plaques in AD brain tissue samples. These data indicate altered cellular communications between microglia in the AD brain.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 10","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667386","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}