Glia最新文献

{"title":"Astrocyte Loss Augments Body Weight Through Reduction in Adipose Sympathetic Outflows.","authors":"Dan Chen, Yale Y Yang, Yunlei Yang","doi":"10.1002/glia.24673","DOIUrl":"https://doi.org/10.1002/glia.24673","url":null,"abstract":"<p><p>Emerging evidence indicates that astrocytes modulate energy metabolism and homeostasis. However, one important but poorly understood element is the necessity of astrocytes in the control of body weight. Here, we apply viral vector-assisted brain-region selective loss of astrocytes to define physiological roles played by astrocytes in the arcuate nucleus of the hypothalamus (ARH) and to elucidate the involved mechanism. We find that astrocyte loss potently augments body weight in adult mice fed chow or high-fat diet. Mechanistically, we find that the loss of astrocytes reduces adipose tissue norepinephrine (NE) contents and chemogenetic stimulation of adipose tissue sympathetic inputs reverses the astrocyte loss-induced increase in body weight. Collectively, our findings in this study suggest a crucial physiological role of astrocytes in preventing diet-induced energy surfeit and obesity by modulating adipose tissue lipid metabolism through central sympathetic outflows to adipose tissues.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA Sequencing Uncovers Molecular Features Underlying the Disrupted Neurogenesis Following Traumatic Brain Injury.","authors":"Cong Liu, Fang-Hong Shao, Xuan-Cheng He, Hong-Zhen Du, Chang-Mei Liu, Bing Zhou, Zhao-Qian Teng","doi":"10.1002/glia.24671","DOIUrl":"https://doi.org/10.1002/glia.24671","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with limited effective treatment strategies. Endogenous neural stem cells (NSCs) give rise to neurons and glial cells throughout life. However, NSCs are more likely to differentiate into glial cells rather than neurons at the lesion site after TBI and the underlying molecular mechanism remains largely unknown. Here, we performed large-scale single-cell transcriptome sequencing of subventricular zone (SVZ) NSCs and NSCs-derived cells in the mouse brain, and provide molecular evidence for previous observations that glial differentiation of NSCs prevails after TBI. In addition, we show that the disrupted neurogenesis following TBI is caused by the reduction of a NSC subcluster (NSC-4) expressing the neuronal gene Tubb3. Finally, we demonstrate that the transcriptional factor Dlx2 is significantly downregulated in NSC-4, and Dlx2 overexpression is sufficient to drive NSCs towards neuronal lineage differentiation at the expense of astrocytic lineage differentiation under pro-inflammatory conditions.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced White Matter Damage and Lower Neuroinflammatory Potential of Microglia and Macrophages in Hri/Eif2ak1^-/- Mice After Contusive Spinal Cord Injury.","authors":"Sujata Saraswat Ohri, Scott A Myers, Benjamin Rood, Brandon L Brown, Paula M Chilton, Lukasz Slomnicki, Yu Liu, George Z Wei, Kariena R Andres, Divya Mohan, Russell M Howard, Scott R Whittemore, Michal Hetman","doi":"10.1002/glia.24669","DOIUrl":"https://doi.org/10.1002/glia.24669","url":null,"abstract":"<p><p>Cellular stressors inhibit general protein synthesis while upregulating stress response transcripts and/or proteins. Phosphorylation of the translation factor eIF2α by one of the several stress-activated kinases is a trigger for such signaling, known as the integrated stress response (ISR). The ISR regulates cell survival and function under stress. Here, germline knockout mice were used to determine contributions by three major ISR kinases, HRI/EIF2AK1, GCN2/EIF2AK4, and PKR//EIF2AK2, to pathogenesis of moderate contusive spinal cord injury (SCI) at the thoracic T9 level. One-day post-injury (dpi), reduced levels of peIF2α were found in Hri^-/- and Gcn2^-/-, but not in Pkr^-/- mice. In addition, Hri^-/- mice showed attenuated expression of the downstream ISR transcripts, Atf4 or Chop. Such differential effects of SCI-activated ISR correlated with a strong or moderate enhancement of locomotor recovery in Hri^-/- or Gcn2^-/- mice, respectively. Hri^-/- mice also showed reduced white matter loss, increased content of oligodendrocytes (OL) and attenuated neuroinflammation, including decreased lipid accumulation in microglia/macrophages. Cultured neonatal Hri^-/- OLs showed lower ISR cytotoxicity. Moreover, cell autonomous reduction in neuroinflammatory potential was observed in microglia and bone marrow-derived macrophages derived from Hri^-/- mice. These data identify HRI as a major positive regulator of SCI-associated secondary injury. In addition, targeting HRI may enable multimodal neuroprotection to enhance functional recovery after SCI.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Responses to Alzheimer's Disease Pathology: Insights From “Omics” Studies","authors":"Aquene N. Reid,&nbsp;Suman Jayadev,&nbsp;Katherine E. Prater","doi":"10.1002/glia.24666","DOIUrl":"10.1002/glia.24666","url":null,"abstract":"<div>\u0000 \u0000 <p>Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes that are expressed in a microglia-specific manner. However, while alterations in microglial morphology and gene expression are observed in human postmortem brain tissue, the mechanisms by which microglia drive and contribute to AD pathology remain ill-defined. Numerous mouse models have been developed to facilitate the disambiguation of the biological mechanisms underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, the use of multiple technologies including bulk tissue and single cell transcriptomics, epigenomics, spatial transcriptomics, proteomics, lipidomics, and metabolomics have shed light on the heterogeneity of microglial phenotypes and molecular patterns altered in AD mouse models. Each of these 'omics technologies provide unique information and biological insight. Here, we review the literature on the approaches and findings of these methods and provide a synthesis of the knowledge generated by applying these technologies to mouse models of AD.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 3","pages":"519-538"},"PeriodicalIF":5.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial Biologist's Guide to Mass Spectrometry-Based Lipidomics: A Tutorial From Sample Preparation to Data Analysis","authors":"Caitlin E. Randolph,&nbsp;Katherine A. Walker,&nbsp;Ruilin Yu,&nbsp;Connor Beveridge,&nbsp;Palak Manchanda,&nbsp;Gaurav Chopra","doi":"10.1002/glia.24665","DOIUrl":"10.1002/glia.24665","url":null,"abstract":"<p>Neurological diseases are associated with disruptions in the brain lipidome that are becoming central to disease pathogenesis. Traditionally perceived as static structural support in membranes, lipids are now known to be actively involved in cellular signaling, energy metabolism, and other cellular activities involving membrane curvature, fluidity, fusion or fission. Glia are critical in the development, health, and function of the brain, and glial regulation plays a major role in disease. The major pathways of glial dysregulation related to function are associated with downstream products of metabolism including lipids. Taking advantage of significant innovations and technical advancements in instrumentation, lipidomics has emerged as a popular omics discipline, serving as the prevailing approach to comprehensively define metabolic alterations associated with organismal development, damage or disease. A key technological platform for lipidomics studies is mass spectrometry (MS), as it affords large-scale profiling of complex biological samples. However, as MS-based techniques are often refined and advanced, the relative comfort level among biologists with this instrumentation has not followed suit. In this review, we aim to highlight the importance of the study of glial lipids and to provide a concise record of best practices and steps for MS-based lipidomics. Specifically, we outline procedures for glia lipidomics workflows ranging from sample collection and extraction to mass spectrometric analysis to data interpretation. To ensure these approaches are more accessible, this tutorial aims to familiarize glia biologists with sample handling and analysis techniques for MS-based lipidomics, and to guide non-experts toward generating high quality lipidomics data.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 3","pages":"474-494"},"PeriodicalIF":5.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Cytoskeletal Linker Protein GAS2L1 on Oligodendrocyte and Myelin Development","authors":"Yanping Zou,&nbsp;Yili Jin,&nbsp;Yuqian Yang,&nbsp;Liuning Zhang,&nbsp;Yuanyu Feng,&nbsp;Yu Long,&nbsp;ZhengTao Xu,&nbsp;Yuehua He,&nbsp;Wei Zheng,&nbsp;Shuming Wang,&nbsp;Yongxiang He,&nbsp;Jiong Li,&nbsp;Huiliang Li,&nbsp;Zhigang Luo,&nbsp;Chun Hu,&nbsp;Lin Xiao lead contact","doi":"10.1002/glia.24658","DOIUrl":"10.1002/glia.24658","url":null,"abstract":"<div>\u0000 \u0000 <p>Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS), develop from OL precursor cells (OPCs) through a complex process involving significant morphological changes that are critically dependent on the dynamic interactions between cytoskeletal networks. Growth arrest-specific 2-like protein 1 (GAS2L1) is a cytoskeletal linker protein that mediates the cross-talk between actin filaments and microtubules. However, its role in OL and myelin development remains unknown. Here, we report that GAS2L1 is expressed in both OPCs and mature OLs, and that overexpression or knockdown of <i>Gas2l1</i> in cultured OPCs in vitro impaired or enhanced their differentiation, respectively, while both inhibited their proliferation. We generated a <i>Gas2l1</i>\u0000 ^{\u0000 <i>fl/fl</i>\u0000} mouse line and found that mice with conditional knockout of <i>Gas2l1</i> in OL lineage cells (<i>Olig1-Cre</i>;<i>Gas2l1</i>\u0000 ^{\u0000 <i>fl/fl</i>\u0000}, cKO) showed an increased number of mature OLs and enhanced myelination, as well as a reduction in the branching complexity of OPCs. In addition, an alternative mouse line with postnatally induced <i>Gas2l1</i> ablation specifically in OPCs (<i>Pdfgra-CreER</i>\u0000 ^{\u0000 <i>T2</i>\u0000};<i>Gas2l1</i>\u0000 ^{\u0000 <i>fl/fl</i>\u0000}, iKO) recapitulated the acceleration of OL and myelin development as well as the inhibition of OPC process branching. Furthermore, EdU tracking in <i>Gas2l1</i> iKO mice in vivo and in their OPC cultures in vitro showed both a reduction in OPC proliferation and an increase in OL maturation. Finally, cultured OPCs from iKO mice showed an increase in filopodia extension. Taken together, our results demonstrate an effect of GAS2L1 on the regulation of OL/myelin development and may provide a novel potential therapeutic target for various diseases involving OL/myelin pathology.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 4","pages":"840-856"},"PeriodicalIF":5.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WebSEQ: A New Tool for Democratizing Omics Data Sharing","authors":"Shane A. Liddelow,&nbsp;Ye Zhang,&nbsp;Steven A. Sloan","doi":"10.1002/glia.24646","DOIUrl":"10.1002/glia.24646","url":null,"abstract":"<div>\u0000 \u0000 <p>The relative ease of generation and proliferation of omics datasets has moved considerably faster than the effective dissemination of these data to the scientific community. Despite advancements in making raw data publicly available, many researchers struggle with data analysis and integration. We propose sharing analyzed data through user-friendly platforms to enhance accessibility. Here, we present a free, online tool, for sharing basic omics data in a searchable and user-friendly format. Importantly, it requires no coding or prior computational knowledge to build—only a data spreadsheet. Overall, this tool facilitates the exploration of transcriptomic, proteomic, and metabolomics data, which is crucial for understanding glial diversity and function. This initiative underscores the importance of accessible molecular data in advancing neuroscience research.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 3","pages":"678-682"},"PeriodicalIF":5.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligodendroglia Are Primed for Antigen Presentation in Response to Chronic Stress-Induced Microglial-Derived Inflammation.","authors":"Miguel M Madeira, Zachary Hage, Alexandros G Kokkosis, Kimberly Nnah, Ryan Guzman, Laurel E Schappell, Dimitris Koliatsis, Emran Resutov, Neil A Nadkarni, Gilbert J Rahme, Stella E Tsirka","doi":"10.1002/glia.24661","DOIUrl":"10.1002/glia.24661","url":null,"abstract":"<p><p>Chronic stress is a major contributor to the development of major depressive disorder, one of the leading causes of disability worldwide. Using a model of repeated social defeat stress in mice, we and others have reported that neuroinflammation plays a dynamic role in the development of behavioral deficits consistent with social avoidance and impaired reward responses. Animals susceptible to the model also exhibit hypomyelination in the medial prefrontal cortex, indicative of changes in the differentiation pathway of cells of the oligodendroglial lineage (OLN). We computationally confirmed the presence of immune oligodendrocytes, a population of OLN cells, which express immune markers and myelination deficits. In the current study, we report that microglia are necessary to induce expression of antigen presentation markers (and other immune markers) on oligodendroglia. We further associate the appearance of these markers with changes in the OLN and confirm that microglial changes precede OLN changes. Using co-cultures of microglia and OLN, we show that under inflammatory conditions the processes of phagocytosis and expression of MHCII are linked, suggesting potential priming for antigen presentation by OLN cells. Our findings provide insights into the nature of these OLN cells with immune capabilities, their obligatory interaction with microglia, and identify them as a potential cellular contributor to the pathological manifestations of psychosocial stress.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Depletion, a New Tool in Neuroinflammatory Disorders: Comparison of Pharmacological Inhibitors of the CSF-1R","authors":"David Guenoun,&nbsp;Nathan Blaise,&nbsp;Alexandre Sellam,&nbsp;Julie Roupret-Serzec,&nbsp;Alice Jacquens,&nbsp;Juliette Van Steenwinckel,&nbsp;Pierre Gressens,&nbsp;Cindy Bokobza","doi":"10.1002/glia.24664","DOIUrl":"10.1002/glia.24664","url":null,"abstract":"<p>A growing body of evidence highlights the importance of microglia, the resident immune cells of the CNS, and their pro-inflammatory activation in the onset of many neurological diseases. Microglial proliferation, differentiation, and survival are highly dependent on the CSF-1 signaling pathway, which can be pharmacologically modulated by inhibiting its receptor, CSF-1R. Pharmacological inhibition of CSF-1R leads to an almost complete microglial depletion whereas treatment arrest allows for subsequent repopulation. Microglial depletion has shown promising results in many animal models of neurodegenerative diseases (Alzheimer's disease (AD), Parkinson's disease, or multiple sclerosis) where transitory microglial depletion reduced neuroinflammation and improved behavioral test results. In this review, we will focus on the comparison of three different pharmacological CSF-1R inhibitors (PLX3397, PLX5622, and GW2580) regarding microglial depletion. We will also highlight the promising results obtained by microglial depletion strategies in adult models of neurological disorders and argue they could also prove promising in neurodevelopmental diseases associated with microglial activation and neuroinflammation. Finally, we will discuss the lack of knowledge about the effects of these strategies on neurons, astrocytes, and oligodendrocytes in adults and during neurodevelopment.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 4","pages":"686-700"},"PeriodicalIF":5.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Sclerosis: Glial Cell Diversity in Time and Space","authors":"Susanne M. Kooistra,&nbsp;Lucas Schirmer","doi":"10.1002/glia.24655","DOIUrl":"10.1002/glia.24655","url":null,"abstract":"<p>Multiple sclerosis (MS) is the most prevalent human inflammatory disease of the central nervous system with demyelination and glial scar formation as pathological hallmarks. Glial cells are key drivers of lesion progression in MS with roles in both tissue damage and repair depending on the surrounding microenvironment and the functional state of the individual glial subtype. In this review, we describe recent developments in the context of glial cell diversity in MS summarizing key findings with respect to pathological and maladaptive functions related to disease-associated glial subtypes. A particular focus is on the spatial and temporal dynamics of glial cells including subtypes of microglia, oligodendrocytes, and astrocytes. We contextualize recent high-dimensional findings suggesting that glial cells dynamically change with respect to epigenomic, transcriptomic, and metabolic features across the inflamed rim and during the progression of MS lesions. In summary, detailed knowledge of spatially restricted glial subtype functions is critical for a better understanding of MS pathology and its pathogenesis as well as the development of novel MS therapies targeting specific glial cell types.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 3","pages":"574-590"},"PeriodicalIF":5.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884907","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}