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Red Fluorescent Labeling of Myelin by Membrane-Targeted tdTomato in Transgenic Mouse Lines 膜靶向tdTomato对转基因小鼠髓磷脂的红色荧光标记。

IF 5.5 2区医学

Glia Pub Date : 2026-10-14 DOI: 10.1002/glia.70246

Anja Reinert, Ulrike Winkler, Sandra Goebbels, Lina Komarek, Wiebke Möbius, Henri Seraf Zanker, Karl Schoknecht, Grit Bornschein, Hartmut Schmidt, Robert Fledrich, Ruth M. Stassart, Petra G. Hirrlinger, Klaus-Armin Nave, Hauke B. Werner, Aiman S. Saab, Johannes Hirrlinger

{"title":"Red Fluorescent Labeling of Myelin by Membrane-Targeted tdTomato in Transgenic Mouse Lines","authors":"Anja Reinert, Ulrike Winkler, Sandra Goebbels, Lina Komarek, Wiebke Möbius, Henri Seraf Zanker, Karl Schoknecht, Grit Bornschein, Hartmut Schmidt, Robert Fledrich, Ruth M. Stassart, Petra G. Hirrlinger, Klaus-Armin Nave, Hauke B. Werner, Aiman S. Saab, Johannes Hirrlinger","doi":"10.1002/glia.70246","DOIUrl":"10.1002/glia.70246","url":null,"abstract":"Myelin is a highly complex membranous structure wrapped around axons by oligodendrocytes or Schwann cells in the central and peripheral nervous system, respectively. Fluorescent labeling is widely used to study the structure and dynamics of myelin. Combining structural with functional imaging requires labeling of myelin with red fluorescence, as many functional sensors, including Ca2+ indicators and genetically encoded metabolite sensors, fluoresce in the green spectral range. However, in vivo tools enabling red fluorescent labeling of myelinating cells and their myelin sheaths remain limited. Here, we generated a set of seven transgenic mouse lines expressing a membrane-targeted variant of the red fluorescent protein tdTomato in myelinating oligodendrocytes and Schwann cells throughout the nervous system. The mouse lines provide a variety of expression patterns ranging from wide-spread labeling of myelin to a rather sparse expression, the latter enabling visualization of individual oligodendrocytes and their associated myelin sheaths. In the peripheral nervous system, the pattern of fluorescence in sciatic nerves indicates predominant localization of tdTomato to non-compact myelin compartments including the inner and outer tongues, paranodal loops and Schmidt-Lanterman incisures. In summary, our work provides a set of novel mouse lines with myelin labeled by red fluorescence, which are compatible with diverse imaging modalities in the green spectral range enabling integrated structural and functional imaging.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178315","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

Schwann Cell-Specific ATG7-Dependent Autophagy Protects Myelin in a Mouse Model of Krabbe Disease 雪旺细胞特异性atg7依赖性自噬保护蟹黄病小鼠模型中的髓磷脂

IF 5.5 2区医学

Glia Pub Date : 2026-10-11 DOI: 10.1002/glia.70244

Narayan Dhimal, Aditya Sidharth, Jiajun Zhang, Trina Rudra, Edward Hurley, Pablo M. Paez, Fraser J. Sim, Daesung Shin, M. Laura Feltri

{"title":"Schwann Cell-Specific ATG7-Dependent Autophagy Protects Myelin in a Mouse Model of Krabbe Disease","authors":"Narayan Dhimal, Aditya Sidharth, Jiajun Zhang, Trina Rudra, Edward Hurley, Pablo M. Paez, Fraser J. Sim, Daesung Shin, M. Laura Feltri","doi":"10.1002/glia.70244","DOIUrl":"10.1002/glia.70244","url":null,"abstract":"Krabbe disease (KD) is a lysosomal storage disorder characterized by severe peripheral demyelination caused by mutations in galactosylceramidase (GALC), leading to the accumulation of galactosylceramide and psychosine. Although psychosine toxicity is central to KD pathology, additional mechanisms likely contribute to myelin dysfunction. Because Schwann cells (SCs) play a critical role in myelin maintenance, and GALC deficiency disrupts lysosomal function, we hypothesized that autophagy is altered in SCs during KD progression. Using a SC-specific Galc conditional knockout (Galc SC cKO) mouse model, we identified early changes in autophagy-related protein levels and increased autophagosome abundance during the pre-symptomatic phase, prior to detectable myelin abnormalities. To assess whether autophagy contributes to disease progression, we selectively deleted Atg7, an essential regulator of canonical autophagy, in SCs. Atg7 deletion alone did not affect myelin or behavior, but its loss in Galc SC cKO mice markedly worsened disease severity. Atg7-Galc SC cKO mice exhibited significantly thinner myelin and pronounced deficits in motor performance and nerve conduction, accompanied by altered steady-state levels of autophagy-associated proteins and functional decline. Notably, Atg7 deletion in Galc SC cKO mice did not further increase macrophage abundance, suggesting that the worsened myelin phenotype occurs without additional macrophage recruitment at this stage. Together, these findings demonstrate that autophagy-associated changes occur early in KD and ATG7-dependent pathways play a protective role during disease progression. Modulating ATG7-dependent pathways may therefore warrant further investigation as a strategy to support myelin maintenance in KD and related lysosomal disorders.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163716","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

Myelin Maintenance and Addition Regulate Synaptic Plasticity in the Adult Mouse Cortex 髓磷脂维持和添加调节成年小鼠皮层突触可塑性。

IF 5.5 2区医学

Glia Pub Date : 2026-10-11 DOI: 10.1002/glia.70239

Renee E. Pepper, Kalina Makowiecki, Kimberley A. Pitman, Raphael Ricci, Angela L. Nicoli, Phuong Tram Nguyen, Catherine A. Blizzard, Ben Emery, Carlie L. Cullen, Kaylene M. Young

{"title":"Myelin Maintenance and Addition Regulate Synaptic Plasticity in the Adult Mouse Cortex","authors":"Renee E. Pepper, Kalina Makowiecki, Kimberley A. Pitman, Raphael Ricci, Angela L. Nicoli, Phuong Tram Nguyen, Catherine A. Blizzard, Ben Emery, Carlie L. Cullen, Kaylene M. Young","doi":"10.1002/glia.70239","DOIUrl":"10.1002/glia.70239","url":null,"abstract":"Myelin has the capacity to affect synapse number or plasticity across the lifespan. We report that disrupting oligodendrocyte (OL) and myelin maintenance from P57 (Plp-CreERT2:: Myrffl/fl mice) induces myelin loss and impairs action potential conduction and gross motor performance. By studying sparsely labeled layer V pyramidal neurons in the primary motor cortex of P57 + 60 mice, we determined that apical and basal dendritic spine densities were normal; however, more were large, stable mushroom spines that generated larger amplitude miniature excitatory postsynaptic currents. When we instead prevented OL and myelin addition from P57 (Pdgfrα-CreER:: Myrffl/fl mice), action potential conduction velocity, gross motor performance, and spine densities were normal; however, basal dendritic spine morphology was changed. Without adult myelination, the basal dendrites of P57 + 60 mice retained the morphological characteristics of dendrites in P57 + 0 mice, which have a higher proportion of thin, plastic spines. These data indicate that existing myelin imposes limits on the proportion of spines that become mushroom spines, allowing neurons to remain plastic, while adult myelination is required for spine stabilization within the basal but not apical dendritic compartment. These data show that myelin regulates synaptic plasticity within the motor circuit and offer a potential mechanism by which myelination can influence motor skill learning and/or recall.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165628","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

Molecular Control of Neural Stem Cell Quiescence in the Adult Zebrafish Telencephalon: Established Mechanisms and an Integrative Hypothesis 成年斑马鱼端脑神经干细胞静止的分子调控：已建立的机制和综合假说。

IF 5.5 2区医学

Glia Pub Date : 2026-10-06 DOI: 10.1002/glia.70234

Mathilde Hoareau, Nicolas Diotel, Sepand Rastegar

{"title":"Molecular Control of Neural Stem Cell Quiescence in the Adult Zebrafish Telencephalon: Established Mechanisms and an Integrative Hypothesis","authors":"Mathilde Hoareau, Nicolas Diotel, Sepand Rastegar","doi":"10.1002/glia.70234","DOIUrl":"10.1002/glia.70234","url":null,"abstract":"The zebrafish telencephalon is an excellent model for adult neurogenesis under physiological and regenerative conditions, as many pathways regulating neural stem cell behavior are conserved with mammalian neurogenic niches. Resident radial glial cells (RGCs) serve as neural stem cells in the adult brain and are readily accessible in vivo, because forebrain eversion repositions the ventricular zone to the dorsal surface. Recent studies have revealed substantial heterogeneity among RGCs, including activation-primed cells and deeply quiescent states during homeostasis. Here, we first review the evidence that four mechanisms control quiescence in pallial RGCs: Notch3-mediated lateral inhibition, the neuronal bone morphogenetic protein (BMP)-Id1 axis, the nuclear receptor Nr2f1b, and the secreted factor Midkine-a. The evidence supporting them is unequal, and we state its level for each before asking whether they act together. Notch-mediated lateral inhibition and neuronal BMP-Id1 signaling converge on her4.1, the clearest documented interaction among them, whereas Nr2f1b establishes a deeper dormancy program that resists Notch and BMP inhibition and protects a reserve stem cell pool. Midkine-a is proposed to reinforce quiescence, pending functional validation. Finally, we propose as a hypothesis that these mechanisms act as partially redundant inputs whose relative contributions determine quiescence depth and vary along the antero-posterior axis of the pallium. Together, these findings reframe quiescence as a spectrum of actively maintained conditions rather than a passive default state. These mechanisms are conserved across vertebrates, with implications for understanding why mammalian neural stem cell pools decline with age and injury.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101475","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

Photobiomodulation Ameliorates Alexander Disease Through AMPK/mTOR-Mediated Mitophagy 光生物调节通过AMPK/ mtor介导的线粒体自噬改善亚历山大病。

IF 5.5 2区医学

Glia Pub Date : 2026-10-05 DOI: 10.1002/glia.70229

Nianzhuang Qiu, Jie Zhang, Huan Yi, Sihan Dong, Lei Han, Zhendong Feng, Shumin Gao, Jie Shi, Jia Jia Liu, Ye Wu, Xunbin Wei, Ya Bin Wei

{"title":"Photobiomodulation Ameliorates Alexander Disease Through AMPK/mTOR-Mediated Mitophagy","authors":"Nianzhuang Qiu, Jie Zhang, Huan Yi, Sihan Dong, Lei Han, Zhendong Feng, Shumin Gao, Jie Shi, Jia Jia Liu, Ye Wu, Xunbin Wei, Ya Bin Wei","doi":"10.1002/glia.70229","DOIUrl":"10.1002/glia.70229","url":null,"abstract":"<div>\u0000 \u0000 Alexander disease (AxD) is a rare neurodegenerative disorder characterized by the pathological accumulation of Rosenthal fibers (RFs) and astrocytic inflammation. Despite advances in elucidating its genetic basis, effective therapeutic strategies remain limited. Recent studies indicate that astrocytes in AxD exhibit excessive mitochondrial fragmentation, which may cause mitochondrial dysfunction and inflammatory response. Photobiomodulation (PBM) has been shown to improve mitochondrial function and exert anti-inflammatory effects, suggesting it may be a promising candidate for the treatment of AxD. Here, we report that exposure to 1070-nm infrared light exerts therapeutic efficacy in AxD. Specifically, using the astrocytes derived from AxD patients and a mouse model of AxD, we demonstrate that PBM regulates AMPK/mTOR signaling and promotes mitophagy, thereby attenuating reactive oxygen species production from fragmented mitochondria and subsequent inflammatory status. This study suggests PBM may serve as a novel, non-invasive therapeutic approach for the treatment of AxD.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101493","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

Macrophage-Derived, Rather Than Microglial, Cathepsin B Exacerbates Brain Injury After Ischemic Stroke 巨噬细胞来源的组织蛋白酶B加重缺血性脑卒中后的脑损伤，而不是小胶质细胞。

IF 5.5 2区医学

Glia Pub Date : 2026-10-01 DOI: 10.1002/glia.70228

Wei Kong, Hui Li, Zhou Wu, Yoshinori Hayashi, Hiroshi Nakanishi, Juan Zhao, Yutong Zhang, Hong Qing, Zhenzhen Quan, Junjun Ni

{"title":"Macrophage-Derived, Rather Than Microglial, Cathepsin B Exacerbates Brain Injury After Ischemic Stroke","authors":"Wei Kong, Hui Li, Zhou Wu, Yoshinori Hayashi, Hiroshi Nakanishi, Juan Zhao, Yutong Zhang, Hong Qing, Zhenzhen Quan, Junjun Ni","doi":"10.1002/glia.70228","DOIUrl":"10.1002/glia.70228","url":null,"abstract":"<div>\u0000 \u0000 Neuroimmune responses critically shape the progression and outcome of ischemic stroke, yet the cell type–specific roles of myeloid populations remain incompletely defined. Cathepsin B (CatB), a lysosomal cysteine protease, has been implicated in neuroinflammation, but its contribution from distinct myeloid subsets is unclear. Transient middle cerebral artery occlusion (tMCAO) was induced in wild-type and CatB-deficient mice. Bone marrow chimeras were generated to selectively delete CatB in peripheral myeloid cells or resident microglia. Infarct severity, mortality, myeloid phenotypes, and transcriptional programs were assessed using flow cytometry, immunofluorescence, and bulk and cell type–resolved RNA sequencing. CatB expression was markedly upregulated in ischemic brain myeloid cells, with higher levels in infiltrating macrophages than in microglia. Selective deletion of CatB in peripheral myeloid cells, but not in microglia, significantly reduced infarct size, mortality, and pro-inflammatory gene expression after tMCAO. Transcriptomic analyses showed suppression of inflammatory pathways and preservation of neuronal signaling in mice lacking macrophage-derived CatB. Cell type–resolved RNA sequencing revealed that CatB deficiency shifted infiltrating macrophages toward a pro-resolving, tissue-repair phenotype characterized by increased expression of M2-associated genes, including Chil3. Consistently, CatB-deficient macrophages displayed enhanced pro-resolving polarization in response to ischemic neuron–derived signals in vitro. CatB was also elevated in circulating Ly6C+ monocytes after stroke. These findings identify peripheral myeloid–derived CatB as a key driver of ischemic brain injury and a potential therapeutic target.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101445","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 Computational Framework for Myelin as a Regulator of Temporal Integration, Neuronal Excitability, and Synaptic Plasticity 髓磷脂作为时间整合、神经元兴奋性和突触可塑性调节因子的计算框架。

IF 5.5 2区医学

Glia Pub Date : 2026-09-30 DOI: 10.1002/glia.70231

Daniel O'Sullivan, Aref Pariz, Daniel Trotter, Noor Z. Al Dahhan, Juliet K. Knowles, Paul W. Frankland, Donald Mabbott, Jérémie Lefebvre

{"title":"A Computational Framework for Myelin as a Regulator of Temporal Integration, Neuronal Excitability, and Synaptic Plasticity","authors":"Daniel O'Sullivan, Aref Pariz, Daniel Trotter, Noor Z. Al Dahhan, Juliet K. Knowles, Paul W. Frankland, Donald Mabbott, Jérémie Lefebvre","doi":"10.1002/glia.70231","DOIUrl":"10.1002/glia.70231","url":null,"abstract":"Myelin regulates neural signaling not only by enabling fast conduction but also by dynamically tuning axonal conduction velocity (CV) and thereby shaping spike timing. While activity-dependent myelination is thought to optimize neural communication, how changes in myelin translate into altered single-cell dynamics and plasticity remains unclear. Using a computational modeling approach, we show that disruptions of axonal CV reorganize presynaptic input correlations, leading to systematic changes in postsynaptic excitability, excitation–inhibition balance, and spike-timing-dependent plasticity. By spanning CV regimes associated with healthy myelination, demyelination, and excessive myelination, our simulations illustrate how both deficient and excessive CV could induce maladaptive neuronal dynamics. The incorporation of firing-rate homeostasis into our models further suggests distinct neuronal dynamic consequences for acute versus chronic myelin disruption. Ultimately, these results suggest that axonal CV may serve as a key mechanistic link between myelin plasticity and neural computation, offering a principled framework to interpret the functional consequences of myelin dysregulation in health and disease.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079124","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

4-Methylumbelliferone Restores Age-Related Changes in Perineuronal Nets, Memory, and Neuroinflammation 甲基伞形酮恢复神经周围网络、记忆和神经炎症的年龄相关变化。

IF 5.5 2区医学

Glia Pub Date : 2026-09-30 DOI: 10.1002/glia.70233

Anda Cimpean, Jana Mizerakova, Noelia Martinez-Varea, Dana Marekova, Lucia Machova Urdzikova, James W. Fawcett, Pavla Jendelova, Jessica C. F. Kwok

{"title":"4-Methylumbelliferone Restores Age-Related Changes in Perineuronal Nets, Memory, and Neuroinflammation","authors":"Anda Cimpean, Jana Mizerakova, Noelia Martinez-Varea, Dana Marekova, Lucia Machova Urdzikova, James W. Fawcett, Pavla Jendelova, Jessica C. F. Kwok","doi":"10.1002/glia.70233","DOIUrl":"10.1002/glia.70233","url":null,"abstract":"Aging-associated cognitive decline is closely linked to dysregulated glial activity and chronic neuroinflammation, which together constrain neuronal plasticity. Astrocytes and microglia are key regulators of the brain extracellular matrix (ECM), including perineuronal nets (PNNs), whose accumulation during aging contributes to reduced synaptic flexibility. Targeting ECM–glia interactions therefore represents a promising strategy to modulate neuroinflammatory and plasticity-related processes. Here, we investigated the effects of long-term oral administration of 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan and chondroitin sulfate synthesis, on glial reactivity, ECM remodeling, and cognitive function in aged mice (20–22 months). Aging was associated with PNN remodeling alongside pronounced astrocytic and microglial activation and infiltration of peripheral immune cells. Chronic 4-MU treatment reduced PNN accumulation to levels observed in younger (10-month-old) mice, indicating effective ECM remodeling. Notably, this was accompanied by a marked attenuation of astrocyte and microglial activation and a reduction in immune cell infiltration, suggesting a broad normalization of the neuroinflammatory milieu. Functionally, these glia-associated changes were paralleled by improved recognition memory, with treated aged mice performing at or above the level of younger controls. Long-term 4-MU administration was well tolerated, with no evident adverse effects. Together, our findings identify ECM modulation as a mechanism to regulate glial reactivity and neuroimmune interactions in the aging brain. By targeting hyaluronan-dependent pathways, 4-MU links ECM remodeling to suppression of neuroinflammation and restoration of cognitive function, highlighting its therapeutic potential in age-related neurodegenerative processes.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079081","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

Interleukin-17A Links Obesity-Induced Inflammation to Behavioral Disorders and Autonomic Imbalance 白细胞介素- 17a与肥胖引起的炎症与行为障碍和自主神经失衡有关

IF 5.5 2区医学

Glia Pub Date : 2026-09-25 DOI: 10.1002/glia.70237

Jing-Ting Fu, Ya-Hsin Liu, Hui-Ting Huang, Yu-Min Kuo, Pei-Chun Chen, Po-See Chen, Shun-Fen Tzeng

{"title":"Interleukin-17A Links Obesity-Induced Inflammation to Behavioral Disorders and Autonomic Imbalance","authors":"Jing-Ting Fu, Ya-Hsin Liu, Hui-Ting Huang, Yu-Min Kuo, Pei-Chun Chen, Po-See Chen, Shun-Fen Tzeng","doi":"10.1002/glia.70237","DOIUrl":"https://doi.org/10.1002/glia.70237","url":null,"abstract":"<div>\u0000 \u0000 Obesity is increasingly recognized as a chronic inflammatory condition, often driven by prolonged high-fat diet (HFD) consumption. Beyond causing metabolic dysregulation, obesity can disrupt immune–brain communication, contributing to the development of emotional disorders. During the early stages of HFD exposure, proinflammatory cytokines such as interleukin-1β (IL-1β), Tumor necrosis factor-alpha (TNF-α), and IL-6 are markedly elevated, but their levels typically return to baseline over time. Despite this normalization, persistent neuroinflammation and gliosis are observed, suggesting that adaptive immune mediators may play a role in chronic neuropathology. In our study using male C57BL/6 mice, 12 and 16 weeks of HFD-induced obesity increased plasma IL-17A levels, a key cytokine produced by CD4+ T helper 17 (Th17) cells, and upregulated IL-17A mRNA expression in the hypothalamus. Peripheral administration of recombinant IL-17A via intraperitoneal (i.p.) injection every 2 days for 4 weeks induced depressive and anxiety-like behaviors, accompanied by enhanced microgliosis in emotion-related brain regions and infiltration of CD4+/IL-17A+ cells in the meninges. Peripheral IL-17A administration also reduced heart rate variability (HRV), accompanied by altered HRV-derived indices, suggesting disruption of autonomic nervous system (ANS) regulation. Systemic administration of plasma derived from mice with 12-week HFD-induced obesity (OB plasma) evoked depressive and anxiety-like phenotypes, as well as ANS dysfunction. Neutralizing anti-IL-17A in the OB plasma effectively blocked these emotional and physiological impairments induced by OB plasma administration. Thus, our findings identify IL-17A as a critical mediator linking metabolic dysfunction, neuroinflammation, and emotional disorders, highlighting its potential as a therapeutic target for obesity-associated depression and anxiety.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 12","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048374","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

Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging 细胞表面标记识别成人海马星形胶质细胞亚群与衰老的异质反应。

IF 5.5 2区医学

Glia Pub Date : 2026-09-24 DOI: 10.1002/glia.70236

Lucía Casares-Crespo, Marife Cano-Jaimez, Raquel Anta, Alba Ripollés-Boix, Fabián Robledo-Yagüe, Sheila Zúñiga-Trejos, Helena Mira

{"title":"Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging","authors":"Lucía Casares-Crespo, Marife Cano-Jaimez, Raquel Anta, Alba Ripollés-Boix, Fabián Robledo-Yagüe, Sheila Zúñiga-Trejos, Helena Mira","doi":"10.1002/glia.70236","DOIUrl":"10.1002/glia.70236","url":null,"abstract":"Astrocyte diversity is currently expanding both between and within specific brain regions. Here, we assessed the spatial distribution and transcriptomic profile of two hippocampal astrocyte subpopulations, defined by combinatorial expression of the cell surface astrocyte markers ACSA-1 or GLAST/SLC1A3, and ACSA-2 or ATP1B2. Fluorescence activated cell sorting and genome-wide transcriptomics by bulk RNAseq uncovered distinct transcriptional signatures of the two astrocyte subsets and highlighted heterogeneous responses during aging. The most abundant ATP1B2/GLAST double-positive astrocytes corresponded to functionally specialized glial cells with increased protein glycosylation and stable gene expression patterns. Signatures related to mitochondrial respiration and cholesterol metabolism were induced during aging in ATP1B2 single-positive astrocytes, while cell adhesion genes from the γ-protocadherin cluster were repressed in double-positive astrocytes. Heterochronic co-culture assays with primary neurons show the loss of synaptogenic function of old ATP1B2/GLAST astrocytes. Our results complement previous studies demonstrating the presence of morphological and molecular astrocyte heterogeneity within the hippocampus, and uncover differences among astrocyte subsets in their transcriptomic response to aging.","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 11","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035846","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