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IF 5.1 2区医学

Glia Pub Date : 2026-04-17

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IF 5.1 2区医学

Glia Pub Date : 2026-04-17

引用次数: 0

IF 5.1 2区医学

Glia Pub Date : 2026-04-13

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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}

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IF 5.1 2区医学

Glia Pub Date : 2026-04-13

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}

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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