Glia最新文献 - Book学术

Spleen Tyrosine Kinase (SYK) is Necessary for cGAS-STING Signaling in Müller Glia and Visual Function Deficits in Diabetic Mice 脾酪氨酸激酶（SYK）是糖尿病小鼠<s:1>勒神经胶质细胞cGAS-STING信号传导和视觉功能缺陷所必需的

IF 5.1 2区医学

Glia Pub Date : 2026-04-13 DOI: 10.1002/glia.70155

Esma I. Yerlikaya, Siddharth Sunilkumar, Sandeep M. Subrahmanian, Allyson L. Toro, Clay T. Yeager, Kashif A. Shaikh, Edward W. Harhaj, Alistair J. Barber, Michael D. Dennis

{"title":"Spleen Tyrosine Kinase (SYK) is Necessary for cGAS-STING Signaling in Müller Glia and Visual Function Deficits in Diabetic Mice","authors":"Esma I. Yerlikaya, Siddharth Sunilkumar, Sandeep M. Subrahmanian, Allyson L. Toro, Clay T. Yeager, Kashif A. Shaikh, Edward W. Harhaj, Alistair J. Barber, Michael D. Dennis","doi":"10.1002/glia.70155","DOIUrl":"10.1002/glia.70155","url":null,"abstract":"It is well established that inflammation contributes to the ocular complications caused by diabetes; however, the specific molecular events that drive diabetes-induced pro-inflammatory signaling in the retina remain to be fully elucidated. This study investigated the role of Müller glial spleen tyrosine kinase (SYK) in diabetes-induced retinal complications. Hyperglycemic culture conditions increased mitochondrial membrane permeability and cytosolic mitochondrial DNA content in human MIO-M1 Müller cells and enhanced cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling, nuclear factor-κB (NF-κB) activation, and inflammatory cytokine expression. STING inhibition reduced inflammatory cytokine expression in cells exposed to hyperglycemic conditions by acting downstream of the increase in cytosolic mitochondrial DNA levels. In cells exposed to either hyperglycemic conditions or the STING agonist diABZI, SYK signaling was necessary for cGAS-STING pathway activation. Inhibition of SYK-dependent cGAS-STING signaling reduced the expression of inflammatory cytokines, including IL1β, CCL2, and CCL5, under hyperglycemic conditions. In the retina of diabetic mice, Müller glia-specific SYK deletion reduced glial activation and attenuated inflammatory cytokine expression. Müller glia-specific SYK deletion also prevented diabetes-induced retinal thinning and visual function deficits in spatial frequency threshold and contrast sensitivity. The data support an essential role for Müller glial SYK in diabetes-induced retinal inflammation and the development of functional deficits in vision.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669271","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}

引用次数: 0

Post-Mortem Delay Induces Distinct Transcriptional and Morphological Changes in Microglia With Age-Specific Patterns 死后延迟诱导具有年龄特异性模式的小胶质细胞明显的转录和形态学变化。

IF 5.1 2区医学

Glia Pub Date : 2026-04-06 DOI: 10.1002/glia.70144

Stanislav Kozlov, Eduard Schmidt, Heidi Theis, Elena De Domenico, Marc D. Beyer, Annett Halle

{"title":"Post-Mortem Delay Induces Distinct Transcriptional and Morphological Changes in Microglia With Age-Specific Patterns","authors":"Stanislav Kozlov, Eduard Schmidt, Heidi Theis, Elena De Domenico, Marc D. Beyer, Annett Halle","doi":"10.1002/glia.70144","DOIUrl":"10.1002/glia.70144","url":null,"abstract":"<div>\u0000 \u0000 Postmortem tissue is a vital resource for transcriptomic studies of human microglia, yet the influence of postmortem delay (PMD) on microglial states, particularly in aging, remains insufficiently understood. Here, we examined the impact of PMD in young and aged male mice, with a particular focus on aging-associated primed microglia. We performed bulk RNA sequencing on Dectin-1-high and -low microglia isolated after PMDs of 0, 6, or 12 h, with Dectin-1 serving as a marker of primed microglia. PMD did not obscure aging-associated signatures or reduce viability, but consistently altered gene expression profiles. Upregulated pathways included mitochondrial, heat-shock, and apoptosis regulation responses, while actin cytoskeleton regulation was downregulated. These effects differed between young and aged animals, and between primed and non-primed microglia, with attenuation in primed subsets. Reanalysis of human single-cell and single-nucleus datasets confirmed that PMD-associated signatures identified in our dataset, particularly those in aging-related Dectin-1low microglia, correlate with PMD in human datasets and display similar enrichment patterns. Morphological analysis in fixed brain tissue from the same animals revealed that postmortem delay reduced the cell shape complexity of cortical microglia in young mice, mimicking morphological changes in the aged brain. In contrast, the morphology of aged microglia remained unchanged by postmortem delay. Taken together, these findings suggest that postmortem delay introduces subtle yet consistent transcriptional and morphological changes in microglia that can confound the interpretation of aging- and disease-related phenotypes. These results highlight the importance of controlling for postmortem effects in studies using human postmortem tissue.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626638","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}

引用次数: 0

RXR Gamma Enables Oligodendrocyte Differentiation by Suppressing Sonic Hedgehog Signaling RXR γ通过抑制Sonic Hedgehog信号传导促进少突胶质细胞分化。

IF 5.1 2区医学

Glia Pub Date : 2026-04-03 DOI: 10.1002/glia.70151

Vito Antonio Baldassarro, Quentin Brassart, Valérie Fraulob, Laura Calzà, Wojciech Krezel

{"title":"RXR Gamma Enables Oligodendrocyte Differentiation by Suppressing Sonic Hedgehog Signaling","authors":"Vito Antonio Baldassarro, Quentin Brassart, Valérie Fraulob, Laura Calzà, Wojciech Krezel","doi":"10.1002/glia.70151","DOIUrl":"10.1002/glia.70151","url":null,"abstract":"Overcoming remyelination failure is one of the main targets in therapeutic strategies for multiple sclerosis. This process requires the differentiation of oligodendrocyte precursor cells (OPCs) to mature myelinating oligodendrocytes (OLs), a process known to be controlled by thyroid hormone, nuclear receptors, and sonic hedgehog (SHH). Retinoid X receptor gamma (RXRg) is one of the nuclear receptors acting as a positive regulator of remyelination, but little is known about its mechanisms of function. Using transcriptomic and pharmacological analysis of primary neural stem cell-derived OPCs, we show that RXRg is involved in the induction of the thyroid hormone-driven differentiation process and in refining it toward an oligodendrogenic cell fate. RXRg also emerged as an important negative modulator of SHH expression and signaling, as Shh and additional genes from this pathway were found to be strongly upregulated in Rxrg−/− OPCs. An inhibition of SHH signaling by cyclopamine or GANT61 entirely normalized the differentiation deficit of Rxrg−/− OPCs, but also myelination of newly generated Rxrg−/− OLs. Such data indicate a key role of SHH hyperactivity in the oligodendrogenesis block associated with the absence of RXRg. Importantly, hyperactivation of the SHH pathway by purmorphamine or SAG inhibited the oligodendrogenesis and myelination potential of wild-type OPCs, indicating that SHH hyperactivity can also be a sufficient factor to block OPC differentiation. These results point to RXRg as an important regulator of SHH pathway signaling and underline the need of an optimal, fine-tuning of SHH signaling to assure successful oligodendrogenesis.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615473","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}

引用次数: 0

Glia Are Bussin’: How Single-Cell and Spatial Transcriptomics Enlighten the Role of Neuroglia in Spinal Cord Injury and Regeneration 神经胶质细胞是活跃的：单细胞和空间转录组学如何启发神经胶质细胞在脊髓损伤和再生中的作用。

IF 5.1 2区医学

Glia Pub Date : 2026-04-03 DOI: 10.1002/glia.70139

Julio Mejia, Philip J. Horner

{"title":"Glia Are Bussin’: How Single-Cell and Spatial Transcriptomics Enlighten the Role of Neuroglia in Spinal Cord Injury and Regeneration","authors":"Julio Mejia, Philip J. Horner","doi":"10.1002/glia.70139","DOIUrl":"10.1002/glia.70139","url":null,"abstract":"The impact that single-cell and spatial genomic technologies have had on the scientific community since their advent has been widespread and profound. The field of spinal cord injury (SCI) is one such area that has experienced an increased implementation of genomic technologies within recent years. Innovative genomic tools have proven to be particularly useful for delving into the progression of SCI pathology and plasticity that is highly dynamic, temporal, and involves the close coordination and signaling of many different central nervous system resident and non-resident cells. Neuroglia, in particular, have been extensively profiled, resulting in a deeper understanding of how neuroglia phenotypes and molecular signaling interact and progress after a spinal cord injury. In this review, we summarize some of the major discoveries that have enlightened and/or shifted our current understanding of the role of neuroglia in injury potentiation and repair. Additionally, through a meta-analysis of five SCI single-cell time course atlases, we uncover insights and cautions regarding how injury model, time course, sample preparation, cellular categorization, and analytical approach impact the interpretation of any new genomic research in this field.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615539","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}

引用次数: 0

Developmental Profiling of Structural and Functional Maturation in Mouse Corpus Callosum 小鼠胼胝体结构和功能成熟的发育特征。

IF 5.1 2区医学

Glia Pub Date : 2026-04-02 DOI: 10.1002/glia.70152

Hayes Johnson, Maren Beall, Sophia Latifi, Juan Peng, Wenjing Sun

{"title":"Developmental Profiling of Structural and Functional Maturation in Mouse Corpus Callosum","authors":"Hayes Johnson, Maren Beall, Sophia Latifi, Juan Peng, Wenjing Sun","doi":"10.1002/glia.70152","DOIUrl":"10.1002/glia.70152","url":null,"abstract":"As the largest white matter tract within the central nervous system (CNS) to connect two cerebral hemispheres, the corpus callosum axon bundle consists of a mixture of myelinated and unmyelinated axons and plays a crucial role in executing sensory, motor and cognitive functions within the CNS. In this study, we comprehensively characterized progressive alterations in myelination and oligodendrocyte lineage cell densities during the postnatal myelin development and then correlated these structural dynamics to the maturation of axonal impulse conduction within the mouse corpus callosum. In addition, we found that the extracellular spaces between callosal axons were significantly reduced during the first three postnatal weeks in mice, while micron-scale diffusion of small molecule within this region remained largely unaffected and displayed isotropy. However, the glutamate transporter GLT-1 was markedly upregulated within the first 3 postnatal weeks, and its expression was found not only in astrocytes but also in oligodendrocyte lineage cells. Finally, we showed that the ectopic callosal axonal vesicle machinery were not fully matured until the later state of myelin development. In summary, our study provided a dynamic profile of the structural and functional maturation of mouse corpus callosum during postnatal myelin development.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588954","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}

引用次数: 0

Microglial Inhibition Promotes Proliferation and Differentiation of Neural Stem Cells via STAT3/SDF-1/CXCR4 Signaling Pathway in Hypoxic–Ischemic Encephalopathy 缺氧缺血性脑病中小胶质细胞抑制通过STAT3/SDF-1/CXCR4信号通路促进神经干细胞的增殖和分化

IF 5.1 2区医学

Glia Pub Date : 2026-03-26 DOI: 10.1002/glia.70149

Ao Ding, Guiqin Duan, Mingwei Zhu, Li Chen, Jie Luo, Ting Tan, Zilin Li, Wenhui Wang, Jun Wang, Yuan Chen, Ya-Ping Tang

{"title":"Microglial Inhibition Promotes Proliferation and Differentiation of Neural Stem Cells via STAT3/SDF-1/CXCR4 Signaling Pathway in Hypoxic–Ischemic Encephalopathy","authors":"Ao Ding, Guiqin Duan, Mingwei Zhu, Li Chen, Jie Luo, Ting Tan, Zilin Li, Wenhui Wang, Jun Wang, Yuan Chen, Ya-Ping Tang","doi":"10.1002/glia.70149","DOIUrl":"10.1002/glia.70149","url":null,"abstract":"Neonatal hypoxic–ischemic encephalopathy (HIE) may induce substantial neuronal damage. In particular, an overactivation of microglia following HIE represents a pathogenically important process. Previous studies have shown that microglial inhibitors can exert neuroprotective effects in HIE; however, the specific mechanisms underlying these effects have not yet been elucidated. Ligation of the left common carotid artery and exposure to 5% O2 were utilized to produce an HIE model in rats. A number of experimental approaches were then used to determine the effect of a microglial inhibition, achieved via the administration of GW2580, a Csf1r inhibitor, and investigate the mechanisms involved. Our HIE models exhibited substantial brain infarction and were significantly impaired in motor functions (p < 0.01–0.001, in all tests examined). In the infarction areas, the number of microglia, macrophages, and neural stem cells (NSCs) was all dramatically increased over that in sham-injured rats, respectively (p < 0.05–0.001). The administration of GW2580 significantly reduced the numbers of microglia and macrophages, but increased the number of NSCs when compared to those in vehicle-treated HIE models (p < 0.05–0.001). Furthermore, GW2580 significantly ameliorated both the histological and behavioral phenotypes in HIE rats and increased STAT phosphorylation (p < 0.05–0.001). Finally, the inhibition or activation of STAT3 respectively decreased or increased the neuroprotective effects of GW2580 (p < 0.05–0.001). Collectively, our findings demonstrate that the STAT3 signaling pathway plays a critical role in the neuroprotective effects of microglial inhibition and may facilitate the development of novel therapeutic strategies to treat stroke.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508305","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}

引用次数: 0

Conservation of Neuron-Astrocyte Correlated Activity in Developing Sensory Pathways 神经元-星形胶质细胞相关活动在感觉通路发育中的保护作用。

IF 5.1 2区医学

Glia Pub Date : 2026-03-26 DOI: 10.1002/glia.70141

Vered Kellner, Patrick Parker, Dongeun Heo, Xuelong Mi, Mikhail Coen, Guoqiang Yu, Gesine Saher, Loyal A. Goff, Dwight E. Bergles

{"title":"Conservation of Neuron-Astrocyte Correlated Activity in Developing Sensory Pathways","authors":"Vered Kellner, Patrick Parker, Dongeun Heo, Xuelong Mi, Mikhail Coen, Guoqiang Yu, Gesine Saher, Loyal A. Goff, Dwight E. Bergles","doi":"10.1002/glia.70141","DOIUrl":"10.1002/glia.70141","url":null,"abstract":"Neurons in developing sensory organs exhibit prolonged burst firing before the onset of sensory experience. This activity promotes neuronal survival and maturation in central sensory pathways. Within the auditory system, periodic bursts of synaptic glutamate release activate metabotropic glutamate receptors (mGluRs) on astrocytes, resulting in spatially and temporally correlated calcium transients; however, whether this phenomenon occurs in other sensory modalities is unknown. Using in vivo calcium imaging in the midbrain of awake mouse pups before eyelid opening, we show that retina wave-induced burst firing of visual afferents induces correlated waves of astrocyte activity in the superior colliculus (SC), a visual processing region. Glutamate sensor imaging revealed that each neuronal burst resulted in glutamate transients at astrocyte membranes in both developing sensory regions. Calcium transients in SC astrocytes resulted from activation of astrocytic mGluR5 and mGluR3, similar to astrocyte events in the nearby inferior colliculus (IC), which are induced by neuronal burst firing in the cochlea. Astrocyte calcium increased with each neuronal wave in the SC, but only the largest neuronal events triggered astrocyte responses in the IC. Astrocyte transcriptomic analysis suggested differential expression of mGluR3 and mGluR5 between these sensory regions, in accordance with the greater dependence on mGluR5 in IC astrocytes. Despite differences in receptor contribution and temporal features of activity, astrocytes in these different regions exhibited similar overall calcium activity. Thus, neuronal burst firing in developing sensory organs provides a conserved mechanism to synchronize neuronal and astrocyte activity in the brain at a critical stage of development.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519433","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}

引用次数: 0

Inflammatory Mediators Both Directly and Indirectly Promote Microglial Proliferation 炎症介质直接或间接促进小胶质细胞增殖。

IF 5.1 2区医学

Glia Pub Date : 2026-03-19 DOI: 10.1002/glia.70150

Brady P. Hammond, Eugene Hahn, Kelly V. Lee, Bradley J. Kerr, Jason R. Plemel

{"title":"Inflammatory Mediators Both Directly and Indirectly Promote Microglial Proliferation","authors":"Brady P. Hammond, Eugene Hahn, Kelly V. Lee, Bradley J. Kerr, Jason R. Plemel","doi":"10.1002/glia.70150","DOIUrl":"10.1002/glia.70150","url":null,"abstract":"Microglia—the predominant immune cell of the central nervous system (CNS)—possess an astounding capacity for proliferation. In development, this proliferation ensures that microglia are present at a sufficient density to perform their vital functions throughout development and into adulthood. During diseases or following CNS injuries, microglial proliferation similarly promotes an increase in microglial density to respond to damage. However, the governing mechanisms for microglial proliferation remain unknown. While many factors have been suggested to promote microglial proliferation—known as mitogens—or to increase microglial densities both in vitro and in vivo, there has been no standardized comparison of these factors. Here, we screened 22 of these factors in serum-free microglial cultures which more faithfully recapitulate in vivo microglial biology. We confirmed three cytokines—colony stimulating factor-2, interleukin-3 and tumor necrosis factor-ɑ—promote microglia proliferation. We similarly tested the remaining non-mitogenic factors for an indirect ability to regulate microglial proliferation by conditioning media from other CNS cell lineages and measuring the capacity for conditioned media to promote microglial proliferation. Of the tested factors and lineages, only interleukin-1ɑ and interleukin-1β promoted the release of a microglial mitogen from astrocytes, which we confirmed to be CSF2. Together, we demonstrate that in standardized conditions, very few factors that were previously reported to promote microglial proliferation or increase microglial densities, are directly, or indirectly, mitogenic.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484089","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}

引用次数: 0

Single-Nucleus Transcriptomics Reveals Microglial State Transitions and Astrocytic Trajectory Divergence During Glial Remodeling Induced by Intracortical Electrode Implantation 单核转录组学揭示了皮质内电极植入诱导的胶质细胞重塑过程中小胶质细胞状态转变和星形细胞轨迹分化。

IF 5.1 2区医学

Glia Pub Date : 2026-03-15 DOI: 10.1002/glia.70148

Zhi Zhao, Xiaoge Duan, Hanjun Huang, Yuxue Zhang, Meiting Wang, Jiaoqin Qin, Sen Lin, Hailan Chen

{"title":"Single-Nucleus Transcriptomics Reveals Microglial State Transitions and Astrocytic Trajectory Divergence During Glial Remodeling Induced by Intracortical Electrode Implantation","authors":"Zhi Zhao, Xiaoge Duan, Hanjun Huang, Yuxue Zhang, Meiting Wang, Jiaoqin Qin, Sen Lin, Hailan Chen","doi":"10.1002/glia.70148","DOIUrl":"10.1002/glia.70148","url":null,"abstract":"<div>\u0000 \u0000 The foreign body response to intracortical electrodes, characterized by chronic neuroinflammation and glial scar formation, remains a primary cause of long-term functional failure. However, neurons and glial cells' heterogeneity and intercellular signaling mechanisms following electrode implantation remain poorly resolved, which is responsible for direct dysfunction. Here, we applied single-nucleus RNA sequencing (snRNA-seq) to profile the peri-implant microenvironment in rat motor cortex tissue at 3, 25, and 50 days post-electrode implantation. Integrated bioinformatic analyses, including clustering, pseudotemporal trajectory reconstruction, and cell–cell communication inference, revealed a coordinated cellular response. We identified a pathologic microglial subpopulation (marked by Gpnmb, SPP1, and CD63) and a scar-associated astrocytic subtype (characterized by Mctp1 and Lrrc7) that progressively dominate the peri-implant niche. Crucially, we reveal that neurons orchestrate these processes via CX3CL1-CX3CR1 signaling, modulating microglial polarization and PTN-ALK/Ptpprz1 interaction, promoting astrogliosis and scar formation. These findings define the dynamic neuron–glia signaling landscape surrounding chronically implanted electrodes and provide mechanistic insight into how modulating cell–cell communication may improve the long-term biocompatibility of neural interfaces.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462445","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}

引用次数: 0

Correction to “RetSat Knockout Mitigates Hypoxia-Induced Microglial Activation by Enhancing Lipid Droplets Degradation” 更正“RetSat敲除通过增强脂滴降解减轻缺氧诱导的小胶质细胞激活”。

IF 5.1 2区医学

Glia Pub Date : 2026-03-08 DOI: 10.1002/glia.70146

引用次数: 0