IF 5.1 2区医学

Glia Pub Date : 2026-06-07 DOI: 10.1002/glia.70181

Félix Camille Bellier, Lou Zonca, David Holcman, Frédéric Chauveau, Nathalie Rouach, Armelle Rancillac

{"title":"Female Mice Show Stronger Time-of-Day Modulation of Astrocytic Ca2+ Activity in the Sleep-Regulatory Ventrolateral Preoptic Nucleus","authors":"Félix Camille Bellier, Lou Zonca, David Holcman, Frédéric Chauveau, Nathalie Rouach, Armelle Rancillac","doi":"10.1002/glia.70181","DOIUrl":"10.1002/glia.70181","url":null,"abstract":"Astrocytes actively contribute to sleep regulation through intracellular calcium (Ca2+) signaling. Yet, whether astrocytic dynamics within sleep-promoting hypothalamic nuclei vary across the nycthemeral cycle in a sex-dependent manner remains unknown. The ventrolateral preoptic area (VLPO) is a key sleep-promoting nucleus whose neuronal circuitry has been extensively characterized. However, the local astrocytic Ca2+ activity remains poorly defined. Here, we investigated astrocytic Ca2+ signaling in the VLPO of male and female mice across the nycthemeral cycle. Using two-photon Ca2+ imaging in acute VLPO-containing brain slices prepared at Zeitgeber Time (ZT)-2, corresponding to the onset of the rest period, and ZT-14, corresponding to the beginning of the active period, we combined single-event analyses with graph-based network approaches to characterize astrocytic activity across scales. At the level of individual events, spontaneous astrocytic Ca2+ dynamics exhibited marked state dependence and sexual dimorphism. In males, Ca2+ events were smaller and faster at ZT-14 than at ZT-2 (shorter duration and accelerated rise and decay time). In contrast, in females, ZT-14 was characterized by increased event amplitude and frequency, consistent with upregulated Ca2+ signaling during the active phase. At the network level, functional connectivity remained stable in males. Conversely, females exhibited robust network remodeling at ZT-14, including increased astrocyte recruitment, higher node degree of correlations, and a marked rise in the number and proportion of highly connected astrocytes. Together, these findings reveal sex-specific astrocytic signaling strategies in the VLPO across the nycthemeral cycle and underscore the need to incorporate sex as a biological variable in astrocyte-based sleep research.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196385","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

Sustained Neuronal Stimulation Activates Paraventricular Thalamus Astrocytes for Chronicity of Neuropathic Pain in Mice 持续神经元刺激激活室旁丘脑星形胶质细胞对小鼠神经性疼痛的慢性影响。

IF 5.1 2区医学

Glia Pub Date : 2026-06-02 DOI: 10.1002/glia.70183

Yi Zhao, Peiwen Jian, Jin Liu, Mengchan Ou, Qingchao Fan, Yi Kang, Ke Li, Jiefei Shen, Jun Yang, Tao Zhu, Guo Chen, Cheng Zhou

{"title":"Sustained Neuronal Stimulation Activates Paraventricular Thalamus Astrocytes for Chronicity of Neuropathic Pain in Mice","authors":"Yi Zhao, Peiwen Jian, Jin Liu, Mengchan Ou, Qingchao Fan, Yi Kang, Ke Li, Jiefei Shen, Jun Yang, Tao Zhu, Guo Chen, Cheng Zhou","doi":"10.1002/glia.70183","DOIUrl":"10.1002/glia.70183","url":null,"abstract":"<div>\u0000 \u0000 Current treatments for chronic neuropathic pain are limited in efficacy, partly due to the complicated etiology of neuropathic pain chronicity. Ongoing nociceptive inputs from peripheral injuries lead to maladaptive alterations in the central nervous system during the transition from acute to chronic pain, which in turn contribute to the maintenance of chronic pain and reduce the effectiveness of peripheral analgesics. Reactive astrocytes are known to contribute to chronic neuropathic pain in the spinal cord, while how astrocytes contribute to chronic pain in supraspinal nuclei remains unclear. This study reveals that continuous painful stimulation from peripheral injury induces astrocyte reactivity and downregulation of astrocytic Kir4.1 (inward rectifying potassium channel protein 4.1) in the paraventricular thalamus (PVT). In turn, these reactive astrocytes help to maintain neuronal hyperactivity in the PVT and enhance neural projections from PVT to the medial prefrontal cortex (mPFC), which contribute to hyperalgesia in chronic neuropathic pain. Therefore, this study identifies a neuro-glial interaction that mediates chronic pain in supraspinal brain.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148147735","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

A Cross-Disease Microglial Transcriptional Program Characterizes Neurodegeneration and Highlights SPP1 as a Biomarker. 跨疾病小胶质细胞转录程序表征神经变性并突出SPP1作为生物标志物。

IF 5.5 2区医学

Glia Pub Date : 2026-06-01 DOI: 10.1002/glia.70163

Alessandro Palma, Roberta Stefanelli, Francesco Trenta, Chiara Projetti, Greta Massa, Sonia Canterini, Maria Teresa Fiorenza

{"title":"A Cross-Disease Microglial Transcriptional Program Characterizes Neurodegeneration and Highlights SPP1 as a Biomarker.","authors":"Alessandro Palma, Roberta Stefanelli, Francesco Trenta, Chiara Projetti, Greta Massa, Sonia Canterini, Maria Teresa Fiorenza","doi":"10.1002/glia.70163","DOIUrl":"10.1002/glia.70163","url":null,"abstract":"Microglial cells are key players in maintaining brain homeostasis and responding to pathological conditions. Their multifaceted roles in health and disease have garnered significant attention in the context of neurodegeneration. In recent years, single-cell transcriptomic techniques have provided unprecedented insights into microglial heterogeneity, revealing distinct subpopulations and gene expression patterns associated with neuroprotection or neurotoxicity. Here, we dissect the transcriptomic landscape of microglia by leveraging human single-nuclei RNA sequencing datasets from multiple neurodegenerative conditions, including Amyotrophic Lateral Sclerosis, frontotemporal dementia, Alzheimer's disease, aging, and Parkinson's disease. This integrative analysis identifies distinct microglial subpopulations, reflecting functional heterogeneity across diseases and reveals a shared cross-disease microglial transcriptional program associated with inflammatory and neurodegenerative processes. Using a machine learning framework, we further demonstrate that this transcriptional program enables robust discrimination between neurodegenerative and control samples. Experimental validation in primary microglia isolated from a mouse model of Niemann-Pick disease type C, also known as juvenile Alzheimer's disease, supports the conservation of key components of this program and highlights Spp1 as a biomarker of disease-associated microglia states. Overall, this study provides an improved portrait of microglia transcriptional remodeling across neurodegenerative disorders and offers a framework for identifying conserved molecular features that may inform therapeutic strategies aimed at modulating microglial activity to mitigate disease progression and foster neuroprotection.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":"e70163"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727816","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

Targeted Inhibition of MEGF10-Mediated Astrogliosis Reduces Glial Scar Formation and Promotes Neurofunction Recovery in Mice After Stroke. 靶向抑制megf10介导的星形胶质细胞增生可减少脑卒中后小鼠胶质瘢痕形成并促进神经功能恢复

IF 5.5 2区医学

Glia Pub Date : 2026-06-01 DOI: 10.1002/glia.70159

Jingjing Xu, Tongtong Xu, Lin Gan, Shiyu Deng, Qianyuan Lian, Jing Ye, Yiyan Guo, Hanlai Li, Yanqin Geng, Huaitong Yao, Enkhbat Myagmartsend, Wanlu Li, Zhijun Zhang, Guo-Yuan Yang, Won-Suk Chung, Jianfeng Li, Yaohui Tang, Jixian Wang

{"title":"Targeted Inhibition of MEGF10-Mediated Astrogliosis Reduces Glial Scar Formation and Promotes Neurofunction Recovery in Mice After Stroke.","authors":"Jingjing Xu, Tongtong Xu, Lin Gan, Shiyu Deng, Qianyuan Lian, Jing Ye, Yiyan Guo, Hanlai Li, Yanqin Geng, Huaitong Yao, Enkhbat Myagmartsend, Wanlu Li, Zhijun Zhang, Guo-Yuan Yang, Won-Suk Chung, Jianfeng Li, Yaohui Tang, Jixian Wang","doi":"10.1002/glia.70159","DOIUrl":"10.1002/glia.70159","url":null,"abstract":"The formation of glial scar at the chronic stage of neurological disease is mainly attributed to the activation and proliferation of astrocytes, termed astrogliosis. It is documented that astrogliosis-induced glial scar formation following stroke severely impairs neurological recovery. However, the mechanisms underlying astrogliosis remain poorly understood. Herein, we discovered that knockdown of MEGF10, a well-known phagocytic receptor that mediates astrocyte-dependent synapse engulfment, caused G1 phase arrest in astrocytes and downregulated cell cycle-related genes, leading to reduced astrocyte proliferation and activation. Genetic deletion of MEGF10 in astrocytes reduced astrocyte proliferation and activation, glial scar formation, and extracellular matrix deposition, subsequentially decreased brain atrophy and promoted neurofunction recovery of mice after stroke. Leveraging on these findings, we further developed a clinically applicable lipid nanoparticle (LNP) system with good biocompatibility, capable of targeted delivery of MEGF10 siRNA to astrocytes. Injecting these LNPs effectively reduced astrocyte proliferation and activation, minimized glial scar formation, and enhanced neurobehavioral recovery of mice after stroke. Our study unveils a previously unrecognized role of MEGF10 in regulating astrogliosis and provides a clinically translatable strategy for targeted modulating glial scar formation and promoting neurofunction recovery after stroke, suggesting that targeting MEGF10 may represent a new therapeutic approach for treating stroke.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":"e70159"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715371","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

Molecular Characterization and Immune Modulation of Schwann Cells in Vestibular Schwannoma 前庭神经鞘瘤中雪旺细胞的分子特征和免疫调节

IF 5.1 2区医学

Glia Pub Date : 2026-06-01 DOI: 10.1002/glia.70179

Lu Wang, Yijiang Bai, Guowei Li, Ye He, Guodong Tang, Xuewen Wu

{"title":"Molecular Characterization and Immune Modulation of Schwann Cells in Vestibular Schwannoma","authors":"Lu Wang, Yijiang Bai, Guowei Li, Ye He, Guodong Tang, Xuewen Wu","doi":"10.1002/glia.70179","DOIUrl":"https://doi.org/10.1002/glia.70179","url":null,"abstract":"<div>\u0000 \u0000 Vestibular schwannoma (VS) is a benign tumor originating from the vestibular nerve, and its complex tumor microenvironment presents significant challenges for research. This study employs single-cell transcriptome sequencing to comprehensively investigate the molecular characteristics of Schwann cells within VS and their potential immunoregulatory roles in the tumor microenvironment. We identified a novel subpopulation of Schwann cells, termed Schwann 4, which shows significantly expressed MHC class II molecules and co-enrichment of PI3K signaling, focal adhesion, and cell adhesion-related pathways, suggesting its potential involvement in tumor-immune modulation. Utilizing machine learning models, we pinpointed 179 genes significantly expressed in Schwann 4, with CTSZ emerging as a candidate gene. CTSZ expression is elevated in VS and is significantly correlated with the PI3K pathway. Comparative analysis revealed that CTSZ promotes proliferation in malignant CNS tumors, whereas its role in benign VS appears distinct. Experimental analysis revealed that CTSZ is correlated with regulatory T cells (Tregs) functionality markers via the PVR-TIGIT pathway, suggesting a potential mechanism for Schwann cell-mediated immune modulation. Functional assays further demonstrated that CTSZ knockdown impairs cell migration and focal adhesion kinase activity. Drug sensitivity analyses identified candidate agents such as YM201636 and AT7867, though their applicability to VS requires dedicated validation. This study contributes to understanding the molecular mechanisms of Schwann cells in benign nerve sheath tumors while providing preliminary evidence for future therapeutic investigation.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148128158","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

Sphingosine-1-Phosphate Receptor 1 Regulates Competition Dependent Astrocyte Morphogenesis and Tiling in Murine Cortex 鞘氨醇-1-磷酸受体1调控竞争依赖的小鼠皮层星形细胞的形态发生和平铺

IF 5.1 2区医学

Glia Pub Date : 2026-06-01 DOI: 10.1002/glia.70177

Jean Patrick M. Gonzales, Connor Tuck, Surya Chandra Rao Thumu, Soha Munir, Jaden Harris, Hunain (Zeik) Tariq, Paul Marcelli, Oscar Dominguez, Kaviya Suriyakumar Anbazagan, Sandeep K. Singh

{"title":"Sphingosine-1-Phosphate Receptor 1 Regulates Competition Dependent Astrocyte Morphogenesis and Tiling in Murine Cortex","authors":"Jean Patrick M. Gonzales, Connor Tuck, Surya Chandra Rao Thumu, Soha Munir, Jaden Harris, Hunain (Zeik) Tariq, Paul Marcelli, Oscar Dominguez, Kaviya Suriyakumar Anbazagan, Sandeep K. Singh","doi":"10.1002/glia.70177","DOIUrl":"https://doi.org/10.1002/glia.70177","url":null,"abstract":"Astrocytes are highly abundant in the mammalian brain and coordinate with neurons and other glial cells to regulate neural circuit structure, function, and blood–brain barrier integrity among many to maintain proper brain homeostasis. Astrocytes perform most of these functions owing to their highly complex morphologies and hundreds of thousands of fine processes that are important in contacting neuronal synapses and other glial cells. In fact, the morphological complexity of astrocytes is regulated by the presence and activity of neurons and helps establish astrocyte territory/tiling in a nonoverlapping pattern; however, the mechanisms of astrocyte tiling are not well characterized. Using a human astrocyte-mouse neuron coculture system, we previously showed that sphingosine-1-phosphate receptor 1 (S1PR1) regulates astrocyte morphogenesis in a neuronal contact dependent manner. In this study, we find that S1PR1 regulates astrocyte morphogenesis in vivo. Using astrocyte-specific S1PR1 knockout mouse models and adeno-associated viral labeling methods, we show that S1PR1 is crucial in establishing competition driven astrocyte tiling and morphogenesis in the developing brain. Furthermore, we show that JAK-STAT3 signaling regulates neuronal contact induced expression of S1PR1 in cocultured astrocytes. These studies therefore uncover a lipid signaling receptor as a major regulator of astrocyte morphogenesis and tiling in murine cortical layers.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 8","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148128153","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

A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants. 斑马鱼pde6c突变体从光感受器变性到再生过程中小胶质细胞状态的动态变化。

IF 5.5 2区医学

Glia Pub Date : 2026-06-01 DOI: 10.1002/glia.70158

Darshini Ravishankar, Yuki Takeuchi, Ichiro Masai

{"title":"A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants.","authors":"Darshini Ravishankar, Yuki Takeuchi, Ichiro Masai","doi":"10.1002/glia.70158","DOIUrl":"10.1002/glia.70158","url":null,"abstract":"Microglia, brain-resident immune cells, maintain brain homeostasis. However, homeostatic microglia dynamically change into disease-associated microglia in human neurodegenerative diseases. Furthermore, microglia-mediated inflammation is required to initiate neuronal regeneration in zebrafish brain. To understand how functional states of microglia are regulated in response to neuronal degeneration and regeneration, we focused on pde6c mutants, a chronic photoreceptor degeneration zebrafish model. We conducted scRNA-seq analysis on microglia in wild-type sibling and pde6c mutant retinas at the onset of photoreceptor degeneration (5 dpf) and Müller glia-mediated neuronal regeneration (4 wpf). At 5 dpf, retinal microglia consist of three clusters, which correspond to homeostatic, degeneration-response, and stress-response microglia, respectively. The degeneration-response cluster expands in pde6c mutants and expresses genes for neuroprotection and tissue repair. At 4 wpf, retinal microglia comprise four clusters, two of which are specifically produced in pde6c mutants and approach the photoreceptor layer. Furthermore, another cluster is prominently localized in the retinal stem cell niche and shows a transcriptomic profile similar to that of neurogenic-associated microglia (NAM). Comparison of transcriptomic similarity between 4 wpf and 5 dpf microglial clusters revealed that each 4 wpf microglial cluster inherits characteristics of homeostatic, degeneration-response, and stress-response state of 5 dpf microglia in different combinations. Thus, there is a unique heterogeneity of microglia in the initial stage of Müller glia-mediated regeneration. Taken together, our findings reveal a dynamic change of retinal microglia during the transition from photoreceptor degeneration to Müller glia-mediated neuronal regeneration in zebrafish.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 6","pages":"e70158"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696893","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

Specific Deletion of Interleukin-1 Beta in Microglia Improves Acute Outcome and Modulates Neurogenesis After Ischemic Stroke 小胶质细胞中白细胞介素-1 β的特异性缺失改善急性预后并调节缺血性卒中后的神经发生。

IF 5.1 2区医学

Glia Pub Date : 2026-05-28 DOI: 10.1002/glia.70164

Alba Grayston, Margarida Baptista, Kelly Wemyss, Ruby Taylor, Grace Cullen, Syeda S. Jafree, Nadim Luka, Joshua R. Cox, Joanne E. Konkel, David Brough, Stuart M. Allan, Emmanuel Pinteaux

{"title":"Specific Deletion of Interleukin-1 Beta in Microglia Improves Acute Outcome and Modulates Neurogenesis After Ischemic Stroke","authors":"Alba Grayston, Margarida Baptista, Kelly Wemyss, Ruby Taylor, Grace Cullen, Syeda S. Jafree, Nadim Luka, Joshua R. Cox, Joanne E. Konkel, David Brough, Stuart M. Allan, Emmanuel Pinteaux","doi":"10.1002/glia.70164","DOIUrl":"10.1002/glia.70164","url":null,"abstract":"Interleukin-1 (IL-1) signaling is a major driver of post-ischemic neuroinflammation, yet the cell- and isoform-specific roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, remain incompletely defined in the context of stroke. Microglia rapidly express IL-1α after cerebral ischemia, whereas IL-1β expression is delayed and restricted to a small subset of microglia and infiltrating immune cells. Here, we investigated for the first time the specific contribution of microglial-derived IL-1β to acute injury and post-stroke neurorepair after transient middle cerebral artery occlusion in male and female mice, through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Deletion of microglial IL-1β improved acute neurological outcomes, reduced neutrophil accumulation in the ischemic brain, and dampened systemic inflammatory cytokines. These effects were most evident during the acute phase and in females in mice. In contrast, long-term functional recovery was largely unaffected. However, microglial IL-1β deletion differentially regulated post-stroke neurogenesis, enhancing subventricular zone neurogenic responses and ectopic neuroblast migration while limiting hippocampal neurogenesis. Together, these findings identify microglial IL-1β as a key amplifier of early inflammatory injury after stroke, exerting region-specific effects on neurogenic niches, and highlight distinct, non-redundant roles for microglial IL-1 isoforms in ischemic brain injury and repair.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040455","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

Walnut-Derived Extracellular Vesicles Orchestrate a Pre-Regenerative Niche via c-Myc Mediated Metabolic Reprogramming 核桃衍生的细胞外囊泡通过c-Myc介导的代谢重编程协调预再生生态位。

IF 5.1 2区医学

Glia Pub Date : 2026-05-28 DOI: 10.1002/glia.70168

Junyang Gao, Genzhong Xu, Nianci Huo, Yuan Liu, Hui Zhou, Jiaqi Liu, Saichao Zhou, Siyao Liu, Ningning Yang, Nan Zhou

{"title":"Walnut-Derived Extracellular Vesicles Orchestrate a Pre-Regenerative Niche via c-Myc Mediated Metabolic Reprogramming","authors":"Junyang Gao, Genzhong Xu, Nianci Huo, Yuan Liu, Hui Zhou, Jiaqi Liu, Saichao Zhou, Siyao Liu, Ningning Yang, Nan Zhou","doi":"10.1002/glia.70168","DOIUrl":"10.1002/glia.70168","url":null,"abstract":"<div>\u0000 \u0000 Peripheral nerve injury (PNI) remains a major regenerative challenge, in part because the post-injury microenvironment can disrupt Schwann cell (SCs) homeostasis. Walnuts (Juglans regia) have long been used in ethnomedicine for perceived neurotrophic or neuroprotective benefits, a view historically linked to their resemblance to the brain. To examine whether this traditional concept can be leveraged as a nanotherapeutic approach, we isolated walnut-derived extracellular vesicles (WEVs) and evaluated their effects on peripheral nerve repair. We found that WEVs are readily internalized by SCs and can help establish a “pre-regenerative niche,” defined here as a permissive metabolic microenvironment that supports repair. Mechanistically, WEVs appear to engage a c-Myc-mediated transcriptional program that shifts SC metabolism toward aerobic glycolysis and increases lactate export, consistent with activation of a glia-to-neuron lactate shuttle. In parallel, WEVs may stabilize the glial bioenergetic hub by limiting stress-induced mitophagy. In a rat sciatic nerve compression model, these changes were associated with preserved mitochondrial ultrastructure in the acute phase, followed by enhanced remyelination, improved motor and sensory outcomes, and attenuated muscle atrophy. Collectively, our findings suggest a mechanistic basis for the reported neuroprotective value of walnuts and identify WEVs as a niche-modulating nanotherapeutic candidate that may promote regeneration by aligning glial metabolic plasticity with neuronal energy demands.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040463","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

Astrocyte Mechanobiology: Linking Biomechanical Forces to Biochemical Signaling in the Central Nervous System 星形胶质细胞力学生物学：将生物力学力与中枢神经系统的生化信号联系起来。

IF 5.1 2区医学

Glia Pub Date : 2026-05-28 DOI: 10.1002/glia.70167

Ana N. Strat, Alima Ahmed, Mariano Viapiano, Preethi S. Ganapathy

{"title":"Astrocyte Mechanobiology: Linking Biomechanical Forces to Biochemical Signaling in the Central Nervous System","authors":"Ana N. Strat, Alima Ahmed, Mariano Viapiano, Preethi S. Ganapathy","doi":"10.1002/glia.70167","DOIUrl":"10.1002/glia.70167","url":null,"abstract":"Astrocytes are the most abundant glial cells within the central nervous system. They are highly specialized mechanosensors able to detect the kinetics and magnitude of external biomechanical stimuli (i.e., matrix substrate stiffness and shear/compressive/tensile biomechanical strains). They integrate these biomechanical cues through a complex interplay of integrins, focal adhesions, junctional proteins and mechanosensitive channels. In development, this crosstalk secures astrocyte fate maturation and heterogeneity. However, in mechanically induced neural injuries, these mechanosensing elements can drive aberrant signaling. The range of astrocyte mechanoresponses in pathology include cytoskeletal remodeling that impacts cellular morphology and stiffness, disrupted calcium signaling, altered metabolism, pro-inflammatory signaling, and disruptive matrix remodeling. Ultimately, these mechanoresponses can form positive feedback loops that aggravate reactive astrogliosis, damage neural tissue, and altogether inhibit neural regeneration in these diseases. This review synthesizes the current knowledge of astrocyte mechanobiology during development and disease, and highlights the importance of continued investigation into the therapeutic potential of mitigating astrocyte mechanodysfunction in disease.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040515","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

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