Glia最新文献 - Book学术

Macrophage Targeting Protects Nerve Structure and Improves Muscle Innervation in a Mouse Model of Charcot-Marie-Tooth 2J. 巨噬细胞靶向保护小鼠Charcot-Marie-Tooth 2J模型的神经结构和改善肌肉神经支配。

IF 5.1 2区医学

Glia Pub Date : 2025-08-04 DOI: 10.1002/glia.70074

Dennis Klein, Neslim Ercan, Xidi Yuan, Ghjuvan' Ghjacumu Shackleford, Anke Claessens, M Laura Feltri, Lawrence Wrabetz, Maurizio D'Antonio, Rudolf Martini

{"title":"Macrophage Targeting Protects Nerve Structure and Improves Muscle Innervation in a Mouse Model of Charcot-Marie-Tooth 2J.","authors":"Dennis Klein, Neslim Ercan, Xidi Yuan, Ghjuvan' Ghjacumu Shackleford, Anke Claessens, M Laura Feltri, Lawrence Wrabetz, Maurizio D'Antonio, Rudolf Martini","doi":"10.1002/glia.70074","DOIUrl":"https://doi.org/10.1002/glia.70074","url":null,"abstract":"In several previous studies, we have shown that macrophage targeting with the CSF-1 receptor specific kinase (c-FMS) inhibitor PLX5622 led to a substantial alleviation of the neuropathy in distinct mouse models of demyelinating Charcot-Marie-Tooth (CMT) 1 forms. However, whether macrophages are also relevant drivers of the neuropathy in axonal CMT2 subtypes has not been studied so far. Here, we investigated the role of macrophages in hemizygous P0T124M mice, which develop a late-onset axonopathy accompanied by macrophage activation at 18 months of age and reflect typical pathological signs of a CMT2J neuropathy. As a tool to target macrophages before disease onset, hemizygous P0T124M mice were treated with PLX5622 from 12 to 18 months of age. Remarkably, treatment with PLX5622 not only ameliorated the peripheral neuropathy to an exceptionally high degree but also prevented distal axonal degeneration and denervation of neuromuscular junctions, leading to preserved motor function in CMT2J mice. These findings highlight macrophage-mediated inflammation as a treatment target in peripheral nerves not only in previously investigated demyelinating but also in axonal CMT neuropathies.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774385","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

Lcn2-Induced Oligodendrocyte Ferroptosis Contributes to White Matter Damage in Chronic Cerebral Hypoperfusion. lcn2诱导的少突胶质细胞铁下垂与慢性脑灌注不足的白质损伤有关。

IF 5.1 2区医学

Glia Pub Date : 2025-08-01 DOI: 10.1002/glia.70069

Qian Liu, Jiaxin Liu, Shiqin Li, Jinghan Xu, Peiqi He, Changling Li, Jinghuan Fang, Peiyan Ni, Jian Guo, Li He

{"title":"Lcn2-Induced Oligodendrocyte Ferroptosis Contributes to White Matter Damage in Chronic Cerebral Hypoperfusion.","authors":"Qian Liu, Jiaxin Liu, Shiqin Li, Jinghan Xu, Peiqi He, Changling Li, Jinghuan Fang, Peiyan Ni, Jian Guo, Li He","doi":"10.1002/glia.70069","DOIUrl":"https://doi.org/10.1002/glia.70069","url":null,"abstract":"Chronic cerebral hypoperfusion (CCH) is associated with cognitive impairment and white matter damage. Lipocalin-2 (Lcn2) has been reported to be associated with both white matter lesions and cognitive impairment. Our previous studies revealed an elevation of Lcn2 in astrocytes within white matter following CCH; however, its role in this process remains poorly understood. In this study, we investigated the effects of Lcn2 deficiency on CCH-induced white matter injury using Lcn2 knockout (LKO) mice. LKO mice exhibited improved cognitive performance in both spatial and recognition memory tasks, along with reduced white matter damage following CCH. Mechanistically, we demonstrated that Lcn2 promotes oligodendrocyte ferroptosis both in vivo and in vitro, contributing to white matter lesions. Furthermore, treatment with the ferroptosis inhibitor Fer-1 improved white matter integrity and rescued cognitive function in CCH mice. These findings suggest that Lcn2 exacerbates oligodendrocyte ferroptosis in CCH, playing a pivotal role in white matter injury and cognitive decline.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758809","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

Reduced Accumulation Rate and Morphological Changes of Newly Generated Myelinating Oligodendrocytes in the Corpus Callosum of Aged Mice. 老龄小鼠胼胝体新生成髓鞘少突胶质细胞积累速率降低及形态学改变。

IF 5.1 2区医学

Glia Pub Date : 2025-08-01 DOI: 10.1002/glia.70070

Sasikarn Looprasertkul, Reiji Yamazaki, Yasuyuki Osanai, Nobuhiko Ohno

{"title":"Reduced Accumulation Rate and Morphological Changes of Newly Generated Myelinating Oligodendrocytes in the Corpus Callosum of Aged Mice.","authors":"Sasikarn Looprasertkul, Reiji Yamazaki, Yasuyuki Osanai, Nobuhiko Ohno","doi":"10.1002/glia.70070","DOIUrl":"https://doi.org/10.1002/glia.70070","url":null,"abstract":"The activity of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes (OLs) throughout life drives myelination, which is crucial for rapid neuronal communication. OLs in the aging brain demonstrate a reduced capacity for myelin formation and maintenance, but the underlying differentiation of individual OLs and morphological changes of their myelin in aging remain unclear. Here, we utilized Pdgfra-CreERT2:Tau-mGFP double transgenic mice to selectively label and visualize newly generated OLs in aged (78-week-old) mice and compared them with those in young (8-week-old) mice. We revealed a significantly lower percentage of newly generated OLs that differentiated into mature OLs and a decreased rate of myelinating OLs accumulation in aged mice compared with young mice. Additionally, newly generated myelinating mature OLs in aged mice demonstrated significantly greater height compared with those in young mice. Furthermore, myelin internodes were significantly shorter and significantly fewer in aged mice compared with young mice. Our results indicate age-related impairments in the differentiation efficiency of aged OPCs and age-related morphological changes in OLs. These alterations in newly generated OLs may contribute to impaired myelination, reduced myelin turnover, and disrupted myelin maintenance in aged mice.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758810","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

Cover Image, Volume 73, Issue 9 封面图片，第73卷，第9期

IF 5.1 2区医学

Glia Pub Date : 2025-07-31 DOI: 10.1002/glia.24560

Binri Sasaki, Momo Oishi, Tomoka Aoki, Mai Hyodo, Chinami Onchi, Nanako Yamada, Hitomi Misawa, Momona Yamada, Chikako Hayashi, Kiyotoshi Sekiguchi, Keisuke Hamada, Yuji Yamada, Yamato Kikkawa, Motoyoshi Nomizu, Nobuharu Suzuki

引用次数: 0

Mutations in GFAP Alter Early Lineage Commitment of Organoids. GFAP突变改变类器官的早期谱系归属。

IF 5.1 2区医学

Glia Pub Date : 2025-07-30 DOI: 10.1002/glia.70049

Werner Dykstra, Zuzana Matusova, Rachel A Battaglia, Pavel Abaffy, Nuria Goya-Iglesias, Dolores Pérez-Sala, Henrik Ahlenius, Mikael Kubista, R Jeroen Pasterkamp, Li Li, Jianfei Chao, Yanhong Shi, Lukas Valihrach, Milos Pekny, Elly M Hol

引用次数: 0

Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke. 酸感应PAC通道促进缺血性卒中星形细胞酸中毒。

IF 5.1 2区医学

Glia Pub Date : 2025-07-28 DOI: 10.1002/glia.70073

Yifei Liu, Yun Zhang, Meng Sun, Huiqing Dong, Xinyuan Hu, Tianyi Shen, Liqin Zhou, Lei Zhang, Ting Wang, Zhaobing Gao, Yi Chang, Jing Feng

{"title":"Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke.","authors":"Yifei Liu, Yun Zhang, Meng Sun, Huiqing Dong, Xinyuan Hu, Tianyi Shen, Liqin Zhou, Lei Zhang, Ting Wang, Zhaobing Gao, Yi Chang, Jing Feng","doi":"10.1002/glia.70073","DOIUrl":"https://doi.org/10.1002/glia.70073","url":null,"abstract":"Astrocyte is critically involved in the central nervous system homeostasis and initiates tissue pathology in response to insults to the central nervous system. However, whether and how astrocytes sense micro-environmental changes, such as ischemic stroke-associated acidification, remains largely unknown. Here we show that the proton-activated chloride (PAC) channel is widely expressed in glial cells in the brain and functionally mediates acid-induced chloride influx. Moreover, conditional knockout of the PAC channel in astrocytes, but not in microglia, reduced infarct volume in a mouse model of ischemic stroke induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Rather than the classic role of chloride channels in cell volume dysregulation-related cell death, activation of the PAC channel contributes to cell apoptosis via the Akt/Bax/Caspase 3 pathway in astrocytes and promotes inflammatory mediator release from astrocytes in response to pH oscillation and oxidative stress. Collectively, our results uncover a role of the PAC channel in astrocyte acidosis, providing a potential therapeutic target for neuroprotection in ischemic stroke.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726241","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

The Influence of Schwann Cell Metabolism and Dysfunction on Axon Maintenance. 雪旺细胞代谢和功能障碍对轴突维持的影响。

IF 5.4 2区医学

Glia Pub Date : 2025-07-25 DOI: 10.1002/glia.70071

Rose Follis, Vishwanath V Prabhu, Bruce D Carter

{"title":"The Influence of Schwann Cell Metabolism and Dysfunction on Axon Maintenance.","authors":"Rose Follis, Vishwanath V Prabhu, Bruce D Carter","doi":"10.1002/glia.70071","DOIUrl":"https://doi.org/10.1002/glia.70071","url":null,"abstract":"Schwann cells are the glial cells in the peripheral nervous system responsible for the production of myelin, which is essential for rapid, saltatory conduction in nerves. However, it has become increasingly recognized that Schwann cells are also key regulators of neuron viability and function, especially for sensory neurons. Neurons and Schwann cells form a tightknit, interdependent couple with complex mechanisms of communication that are only beginning to be understood. There is growing evidence that Schwann cell metabolism profoundly influences axons through the release of a variety of metabolites. These glial cells serve as energy depots for axon function, supplying lactate and/or pyruvate during repeated firing and after injury. Lipid metabolism in Schwann cells, which is critical for myelin production, also affects axon viability, such that disruptions in the production or breakdown of lipids can lead to axon dysfunction and subsequent degeneration. Here, we discuss emerging concepts on the mechanisms by which Schwann cell metabolites influence neuron activity and survival, with particular focus on how dysfunction of lipid metabolism can lead to axon degeneration and the development of peripheral neuropathy.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705843","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

Functional Diversity of Two Novel Embryonic Microglial Subpopulations and Their Developmental Trajectories in Developing Mouse Brains. 两个新的胚胎小胶质细胞亚群的功能多样性及其在发育小鼠大脑中的发育轨迹。

IF 5.4 2区医学

Glia Pub Date : 2025-07-25 DOI: 10.1002/glia.70064

Siao Muk Cheng, Chi-Lin Ho, Shiou-Lan Chen, Yi-Te Huang, Pin-Cheng Mao, Tzu-Chia Lin, Jia-Shing Chen, H Sunny Sun, Daw-Yang Hwang, Chun-Hsien Chu

{"title":"Functional Diversity of Two Novel Embryonic Microglial Subpopulations and Their Developmental Trajectories in Developing Mouse Brains.","authors":"Siao Muk Cheng, Chi-Lin Ho, Shiou-Lan Chen, Yi-Te Huang, Pin-Cheng Mao, Tzu-Chia Lin, Jia-Shing Chen, H Sunny Sun, Daw-Yang Hwang, Chun-Hsien Chu","doi":"10.1002/glia.70064","DOIUrl":"https://doi.org/10.1002/glia.70064","url":null,"abstract":"As the primary brain-resident macrophages, embryonic microglia (EM) display functional diversity and significant heterogeneity, which are essential for normal brain development and growth. However, the heterogeneous nature of EM and their developmental trajectory remain contentious. This study isolated individual cells from the brains of embryonic day 14 (E14) mice without using a microglial cell sorting method and subsequently performed single-cell RNA sequencing (scRNA-seq) analysis. Unsupervised subclustering of the microglial population based on gene expression profiles revealed two novel EM subclusters: approximately 60% EM1 (CD68-negative and Iba-1-positive) and about 40% EM2 (CD68- and Iba-1-double-positive). Additionally, bioinformatics analyses indicated that the EM1 cluster represents relatively early and immature microglia with high proliferative capacity. In contrast, the EM2 cluster exhibits a higher expression of genes involved in the stepwise program of microglial development, synaptic phagocytosis, regulation of neuron differentiation and projection, and interaction with other brain cells. To further confirm these findings, double or triple immunofluorescence staining of Iba-1, CD68, or the presynaptic marker synaptophysin demonstrated the presence of the EM1 and EM2 clusters in E14 mouse brains, as well as increased synaptic phagocytosis in the EM2 cluster. Moreover, by monitoring their proportional changes in the brains on postnatal days 1, 14, and 90, our data disclosed the developmental trajectory of the EMs as they transition from CD68-negative to CD68-positive after the postnatal period stages. Overall, this study opens new avenues for exploring the functional diversity and developmental trajectory of EMs during embryonic brain development and growth.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717104","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-Targeted connexin43 Hemichannel Inhibition Prevents Radiation-Induced Energy Transporter Decrease in Neurons and Astrocytic proBDNF Transport to Synapses. 星形胶质细胞靶向连接蛋白43半通道抑制辐射诱导的神经元能量转运蛋白减少和星形胶质细胞proBDNF向突触的转运。

IF 5.4 2区医学

Glia Pub Date : 2025-07-24 DOI: 10.1002/glia.70063

Steffi Schumacher, Sara Neyt, Christian Vanhove, Lien De Schaepmeester, Robrecht Raedt, Katja Witschas, Luc Leybaert

{"title":"Astrocyte-Targeted connexin43 Hemichannel Inhibition Prevents Radiation-Induced Energy Transporter Decrease in Neurons and Astrocytic proBDNF Transport to Synapses.","authors":"Steffi Schumacher, Sara Neyt, Christian Vanhove, Lien De Schaepmeester, Robrecht Raedt, Katja Witschas, Luc Leybaert","doi":"10.1002/glia.70063","DOIUrl":"https://doi.org/10.1002/glia.70063","url":null,"abstract":"Radiation therapy is widely used for treating brain tumors but also comes with off-target effects, including vascular blood-brain barrier (BBB) leakage occurring as an early event 24 h postirradiation. Here we investigated brain X-irradiation (20 Gy) effects on the astrocyte-neuronal axis starting from BBB endothelium and ending at synapses. Making use of immune-characterization of brain slices isolated 24 h after irradiation of rodents, we found significantly decreased neuronal expression of GLUT3 glucose transporters and MCT2 monocarboxylate transporters in M1/S1 cortical areas, with no changes in astrocytic GLUT1 transporters. Pre-irradiation animal treatment with the Cx43 hemichannel blocker TATGap19 targeting astrocytes completely prevented these neuronal alterations. Brain uptake of 18F-deoxy-glucose was decreased in the pre- and infra-limbic cortex 24 h postirradiation, not in other cortical areas, and was prevented by TATGap19 treatment. Electro-encephalographic recordings showed decreased power in delta, theta, beta, and gamma bands, most clearly in S1 cortex 24 h postirradiation. ProBDNF, a precursor of brain-derived neurotrophic factor associated with negative neural effects, was significantly elevated 24 h postirradiation and accompanied by strong activation of its vesicular transport in astrocytes. In particular, proBDNF uptake in astrocytic endfeet at capillary endothelial cells and its VAMP3-associated release at astrocytic extensions to tripartite synapses were both strongly increased and prevented by animal pretreatment with TATGap19. The present data show that astrocytes are a major target for radiotherapeutic intervention whereby Gap19 inhibition of the Cx43 hemichannel membrane leakage pathway prevents radiation-induced alterations in brain glucose handling and activation of vesicular proBDNF transport to tripartite synapses that disturb neural functioning.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697153","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

Suppression of TRPV5 Regulates Microglia-Mediated Neuroinflammation Following Status Epilepticus. 抑制TRPV5调节癫痫持续状态后小胶质细胞介导的神经炎症。

IF 5.4 2区医学

Glia Pub Date : 2025-07-24 DOI: 10.1002/glia.70068

Soojin Park, Se Hoon Kim, Chul Hoon Kim, Kyoung Hoon Jeong, Won-Joo Kim

{"title":"Suppression of TRPV5 Regulates Microglia-Mediated Neuroinflammation Following Status Epilepticus.","authors":"Soojin Park, Se Hoon Kim, Chul Hoon Kim, Kyoung Hoon Jeong, Won-Joo Kim","doi":"10.1002/glia.70068","DOIUrl":"https://doi.org/10.1002/glia.70068","url":null,"abstract":"Neuroinflammation, predominantly associated with glial activation and the release of various inflammatory mediators, is a vital hallmark of the pathophysiology of epilepsy. Numerous studies have indicated that identifying novel factors that diminish neuroinflammatory processes may be important for developing effective therapeutic strategies to prevent neuropathological processes and epileptogenic progression. Transient receptor potential vanilloid 5 (TRPV5) is a highly selective calcium ion channel belonging to the TRPV family. TRPV5 expression has been identified in diverse regions of the brain; however, it remains unknown how TRPV5 is implicated in the pathophysiological features of neurological diseases, including epilepsy. Herein, we show that TRPV5 expression is upregulated in the hippocampus of a pilocarpine-induced status epilepticus (PCSE) model, predominantly in activated microglia. Pharmacological inhibition of TRPV5 using econazole attenuated microglial activation, as indicated by the shift of LPS-stimulated primary hippocampal microglia to a resting state. This inhibition suppressed AKT/NF-κB signaling, reduced NLRP3 inflammasome activity, and decreased proinflammatory cytokine production. Additionally, TRPV5 inhibition reduced hippocampal microglial activation and neuroinflammation following PCSE. These findings suggest that TRPV5 contributes to the regulation of microglial activation, resulting in the suppression of microglia-derived neuroinflammation during the sub-acute phase of epilepsy. In conclusion, the present study suggests that targeting TRPV5 may offer a novel therapeutic approach to managing the neuroinflammatory processes during epileptogenic progression.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705842","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