IF 5.4 2区医学

Glia Pub Date : 2024-07-09 DOI: 10.1002/glia.24576

Malte S. Kaller, Alberto Lazari, Yingshi Feng, Annette van der Toorn, Sebastian Rühling, Christopher W. Thomas, Takahiro Shimizu, David Bannerman, Vladyslav Vyazovskiy, William D. Richardson, Cassandra Sampaio-Baptista, Heidi Johansen-Berg

{"title":"Ablation of oligodendrogenesis in adult mice alters brain microstructure and activity independently of behavioral deficits","authors":"Malte S. Kaller, Alberto Lazari, Yingshi Feng, Annette van der Toorn, Sebastian Rühling, Christopher W. Thomas, Takahiro Shimizu, David Bannerman, Vladyslav Vyazovskiy, William D. Richardson, Cassandra Sampaio-Baptista, Heidi Johansen-Berg","doi":"10.1002/glia.24576","DOIUrl":"10.1002/glia.24576","url":null,"abstract":"Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice leads to learning and memory deficits in a range of behavioral tasks. The current study replicated and re-evaluated evidence for a role of oligodendrogenesis in motor learning, using a complex running wheel task. Further, we found that ablating oligodendrogenesis alters brain microstructure (ex vivo MRI) and brain activity (in vivo EEG) independent of experience with the task. This suggests a role for adult oligodendrocyte formation in the maintenance of brain function and indicates that task-independent changes due to oligodendrogenesis ablation need to be considered when interpreting learning and memory deficits in this model.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1728-1745"},"PeriodicalIF":5.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24576","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562139","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

Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling 胰腺许旺细胞重编程支持癌症相关神经元重塑

IF 5.4 2区医学

Glia Pub Date : 2024-07-03 DOI: 10.1002/glia.24586

Martha M. Rangel-Sosa, Fanny Mann, Sophie Chauvet

{"title":"Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling","authors":"Martha M. Rangel-Sosa, Fanny Mann, Sophie Chauvet","doi":"10.1002/glia.24586","DOIUrl":"10.1002/glia.24586","url":null,"abstract":"The peripheral nervous system is a key regulator of cancer progression. In pancreatic ductal adenocarcinoma (PDAC), the sympathetic branch of the autonomic nervous system inhibits cancer development. This inhibition is associated with extensive sympathetic nerve sprouting in early pancreatic cancer precursor lesions. However, the underlying mechanisms behind this process remain unclear. This study aimed to investigate the roles of pancreatic Schwann cells in the structural plasticity of sympathetic neurons. We examined the changes in the number and distribution of Schwann cells in a transgenic mouse model of PDAC and in a model of metaplastic pancreatic lesions induced by chronic inflammation. Schwann cells proliferated and expanded simultaneously with new sympathetic nerve sprouts in metaplastic/neoplastic pancreatic lesions. Sparse genetic labeling showed that individual Schwann cells in these lesions had a more elongated and branched structure than those under physiological conditions. Schwann cells overexpressed neurotrophic factors, including glial cell-derived neurotrophic factor (GDNF). Sympathetic neurons upregulated the GDNF receptors and exhibited enhanced neurite growth in response to GDNF in vitro. Selective genetic deletion of Gdnf in Schwann cells completely blocked sympathetic nerve sprouting in metaplastic pancreatic lesions in vivo. This study demonstrated that pancreatic Schwann cells underwent adaptive reprogramming during early cancer development, supporting a protective antitumor neuronal response. These finding could help to develop new strategies to modulate cancer associated neural plasticity.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1840-1861"},"PeriodicalIF":5.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496516","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

Integrity of neural extracellular matrix is required for microglia-mediated synaptic remodeling 小胶质细胞介导的突触重塑需要神经细胞外基质的完整性。

IF 5.4 2区医学

Glia Pub Date : 2024-06-30 DOI: 10.1002/glia.24588

Carla Cangalaya, Weilun Sun, Stoyan Stoyanov, Ildiko Rita Dunay, Alexander Dityatev

{"title":"Integrity of neural extracellular matrix is required for microglia-mediated synaptic remodeling","authors":"Carla Cangalaya, Weilun Sun, Stoyan Stoyanov, Ildiko Rita Dunay, Alexander Dityatev","doi":"10.1002/glia.24588","DOIUrl":"10.1002/glia.24588","url":null,"abstract":"Microglia continuously remodel synapses, which are embedded in the extracellular matrix (ECM). However, the mechanisms, which govern this process remain elusive. To investigate the influence of the neural ECM in synaptic remodeling by microglia, we disrupted ECM integrity by injection of chondroitinase ABC (ChABC) into the retrosplenial cortex of healthy adult mice. Using in vivo two-photon microscopy we found that ChABC treatment increased microglial branching complexity and ECM phagocytic capacity and decreased spine elimination rate under basal conditions. Moreover, ECM attenuation largely prevented synaptic remodeling following synaptic stress induced by photodamage of single synaptic elements. These changes were associated with less stable and smaller microglial contacts at the synaptic damage sites, diminished deposition of calreticulin and complement proteins C1q and C3 at synapses and impaired expression of microglial CR3 receptor. Thus, our findings provide novel insights into the function of the neural ECM in deposition of complement proteins and synaptic remodeling by microglia.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1874-1892"},"PeriodicalIF":5.4,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464651","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

Cover Image, Volume 72, Issue 8 封面图片，第 72 卷第 8 期

IF 5.4 2区医学

Glia Pub Date : 2024-06-28 DOI: 10.1002/glia.24407

Sarah Wirth, Annika Schlößer, Antonia Beiersdorfer, Michaela Schweizer, Marcel S. Woo, Manuel A. Friese, Christian Lohr, Katarzyna M. Grochowska

引用次数: 0

Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury 神经炎症反应性星形胶质细胞的形成与围产期白质损伤的不良后果相关。

IF 5.4 2区医学

Glia Pub Date : 2024-06-26 DOI: 10.1002/glia.24575

Patricia Renz, Marel Steinfort, Valérie Haesler, Vera Tscherrig, Eric J. Huang, Manideep Chavali, Shane Liddelow, David H. Rowitch, Daniel Surbek, Andreina Schoeberlein, Amanda Brosius Lutz

{"title":"Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury","authors":"Patricia Renz, Marel Steinfort, Valérie Haesler, Vera Tscherrig, Eric J. Huang, Manideep Chavali, Shane Liddelow, David H. Rowitch, Daniel Surbek, Andreina Schoeberlein, Amanda Brosius Lutz","doi":"10.1002/glia.24575","DOIUrl":"10.1002/glia.24575","url":null,"abstract":"Perinatal white matter injury (WMI) is the leading cause of long-term neurological morbidity in infants born preterm. Neuroinflammation during a critical window of early brain development plays a key role in WMI disease pathogenesis. The mechanisms linking inflammation with the long-term myelination failure that characterizes WMI, however, remain unknown. Here, we investigate the role of astrocyte reactivity in WMI. In an experimental mouse model of WMI, we demonstrate that WMI disease outcomes are improved in mutant mice lacking secretion of inflammatory molecules TNF-α, IL-1α, and C1q known, in addition to other roles, to induce the formation of a neuroinflammatory reactive astrocyte substate. We show that astrocytes express molecular signatures of the neuroinflammatory reactive astrocyte substate in both our WMI mouse model and human tissue affected by WMI, and that this gene expression pattern is dampened in injured mutant mice. Our data provide evidence that a neuroinflammatory reactive astrocyte substate correlates with adverse WMI disease outcomes, thus highlighting the need for further investigation of these cells as potential causal players in WMI pathology.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 9","pages":"1663-1673"},"PeriodicalIF":5.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454168","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

Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord 在轴突切断术前操纵卫星神经胶质细胞可促进发育中的背根神经节中央分支重新长入脊髓

IF 5.4 2区医学

Glia Pub Date : 2024-06-22 DOI: 10.1002/glia.24581

Robin I. Brown, Heather M. Barber, Sarah Kucenas

{"title":"Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord","authors":"Robin I. Brown, Heather M. Barber, Sarah Kucenas","doi":"10.1002/glia.24581","DOIUrl":"10.1002/glia.24581","url":null,"abstract":"The central and peripheral nervous systems (CNS and PNS, respectively) exhibit remarkable diversity in the capacity to regenerate following neuronal injury with PNS injuries being much more likely to regenerate than those that occur in the CNS. Glial responses to damage greatly influence the likelihood of regeneration by either promoting or inhibiting axonal regrowth over time. However, despite our understanding of how some glial lineages participate in nerve degeneration and regeneration, less is known about the contributions of peripheral satellite glial cells (SGC) to regeneration failure following central axon branch injury of dorsal root ganglia (DRG) sensory neurons. Here, using in vivo, time-lapse imaging in larval zebrafish coupled with laser axotomy, we investigate the role of SGCs in axonal regeneration. In our studies we show that SGCs respond to injury by relocating their nuclei to the injury site during the same period that DRG neurons produce new central branch neurites. Laser ablation of SGCs prior to axon injury results in more neurite growth attempts and ultimately a higher rate of successful central axon regrowth, implicating SGCs as inhibitors of regeneration. We also demonstrate that this SGC response is mediated in part by ErbB signaling, as chemical inhibition of this receptor results in reduced SGC motility and enhanced central axon regrowth. These findings provide new insights into SGC-neuron interactions under injury conditions and how these interactions influence nervous system repair.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1766-1784"},"PeriodicalIF":5.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501226","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

Macrophage GIT1 promotes oligodendrocyte precursor cell differentiation and remyelination after spinal cord injury 巨噬细胞 GIT1 促进脊髓损伤后少突胶质前体细胞分化和髓鞘再形成

IF 5.4 2区医学

Glia Pub Date : 2024-06-20 DOI: 10.1002/glia.24577

Hao Liu, Jiang Yi, Chenxi Zhang, Yin Li, Qian Wang, Shenyu Wang, Siming Dai, Ziyang Zheng, Tao Jiang, Peng Gao, Ao Xue, Zhenfei Huang, Fanqi Kong, Yongxiang Wang, Baorong He, Xiaodong Guo, Qingqing Li, Jian Chen, Guoyong Yin, Shujie Zhao

{"title":"Macrophage GIT1 promotes oligodendrocyte precursor cell differentiation and remyelination after spinal cord injury","authors":"Hao Liu, Jiang Yi, Chenxi Zhang, Yin Li, Qian Wang, Shenyu Wang, Siming Dai, Ziyang Zheng, Tao Jiang, Peng Gao, Ao Xue, Zhenfei Huang, Fanqi Kong, Yongxiang Wang, Baorong He, Xiaodong Guo, Qingqing Li, Jian Chen, Guoyong Yin, Shujie Zhao","doi":"10.1002/glia.24577","DOIUrl":"10.1002/glia.24577","url":null,"abstract":"Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 9","pages":"1674-1692"},"PeriodicalIF":5.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425880","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

Deficient brain GABA metabolism leads to widespread impairments of astrocyte and oligodendrocyte function 大脑 GABA 代谢不足会导致星形胶质细胞和少突胶质细胞功能普遍受损。

IF 5.4 2区医学

Glia Pub Date : 2024-06-20 DOI: 10.1002/glia.24585

Jens V. Andersen, Oana C. Marian, Filippa L. Qvist, Emil W. Westi, Blanca I. Aldana, Arne Schousboe, Anthony S. Don, Niels H. Skotte, Petrine Wellendorph

{"title":"Deficient brain GABA metabolism leads to widespread impairments of astrocyte and oligodendrocyte function","authors":"Jens V. Andersen, Oana C. Marian, Filippa L. Qvist, Emil W. Westi, Blanca I. Aldana, Arne Schousboe, Anthony S. Don, Niels H. Skotte, Petrine Wellendorph","doi":"10.1002/glia.24585","DOIUrl":"10.1002/glia.24585","url":null,"abstract":"The neurometabolic disorder succinic semialdehyde dehydrogenase (SSADH) deficiency leads to great neurochemical imbalances and severe neurological manifestations. The cause of the disease is loss of function of the enzyme SSADH, leading to impaired metabolism of the principal inhibitory neurotransmitter GABA. Despite the known identity of the enzymatic deficit, the underlying pathology of SSADH deficiency remains unclear. To uncover new mechanisms of the disease, we performed an untargeted integrative analysis of cerebral protein expression, functional metabolism, and lipid composition in a genetic mouse model of SSADH deficiency (ALDH5A1 knockout mice). Our proteomic analysis revealed a clear regional vulnerability, as protein alterations primarily manifested in the hippocampus and cerebral cortex of the ALDH5A1 knockout mice. These regions displayed aberrant expression of proteins linked to amino acid homeostasis, mitochondria, glial function, and myelination. Stable isotope tracing in acutely isolated brain slices demonstrated an overall maintained oxidative metabolism of glucose, but a selective decrease in astrocyte metabolic activity in the cerebral cortex of ALDH5A1 knockout mice. In contrast, an elevated capacity of oxidative glutamine metabolism was observed in the ALDH5A1 knockout brain, which may serve as a neuronal compensation of impaired astrocyte glutamine provision. In addition to reduced expression of critical oligodendrocyte proteins, a severe depletion of myelin-enriched sphingolipids was found in the brains of ALDH5A1 knockout mice, suggesting degeneration of myelin. Altogether, our study highlights that impaired astrocyte and oligodendrocyte function is intimately linked to SSADH deficiency pathology, suggesting that selective targeting of glial cells may hold therapeutic potential in this disease.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1821-1839"},"PeriodicalIF":5.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425879","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

Nalfurafine promotes myelination in vitro and facilitates recovery from cuprizone + rapamycin-induced demyelination in mice 纳呋拉芬能促进体外髓鞘化，并有助于小鼠从铜绿素+雷帕霉素诱导的脱髓鞘中恢复过来。

IF 5.4 2区医学

Glia Pub Date : 2024-06-20 DOI: 10.1002/glia.24583

Ross van de Wetering, Rabia Bibi, Andy Biggerstaff, Sheein Hong, Bria Pengelly, Thomas E. Prisinzano, Anne C. La Flamme, Bronwyn M. Kivell

{"title":"Nalfurafine promotes myelination in vitro and facilitates recovery from cuprizone + rapamycin-induced demyelination in mice","authors":"Ross van de Wetering, Rabia Bibi, Andy Biggerstaff, Sheein Hong, Bria Pengelly, Thomas E. Prisinzano, Anne C. La Flamme, Bronwyn M. Kivell","doi":"10.1002/glia.24583","DOIUrl":"10.1002/glia.24583","url":null,"abstract":"The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.6–200 nM), clemastine (0.01–100 μM), T3 (30 ng/mL), or vehicle for 5 days. Using immunocytochemistry and confocal microscopy, we found that nalfurafine treatment increased OPC differentiation, oligodendrocyte (OL) morphological complexity, and myelination of nanofibers in vitro. Adult male mice (C57BL/6J) were given a diet containing 0.2% cuprizone and administered rapamycin (10 mg/kg) once daily for 12 weeks followed by 6 weeks of treatment with nalfurafine (0.01 or 0.1 mg/kg), clemastine (10 mg/kg), or vehicle. We quantified the number of OLs using immunofluorescence, gross myelination using black gold staining, and myelin thickness using electron microscopy. Cuprizone + rapamycin treatment produced extensive demyelination and was accompanied by a loss of mature OLs, which was partially reversed by therapeutic administration of nalfurafine. We also assessed these mice for functional behavioral changes in open-field, horizontal bar, and mouse motor skill sequence tests (complex wheel running). Cuprizone + rapamycin treatment resulted in hyperlocomotion, poorer horizontal bar scores, and less distance traveled on the running wheels. Partial recovery was observed on both the horizontal bar and complex running wheel tests over time, which was facilitated by nalfurafine treatment. Taken together, these data highlight the potential of nalfurafine as a remyelination-promoting therapeutic.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1801-1820"},"PeriodicalIF":5.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425890","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

Myelinated peripheral axons are more vulnerable to mechanical trauma in a model of enlarged axonal diameters 在轴突直径增大的模型中，有髓鞘的外周轴突更容易受到机械创伤的影响。

IF 5.4 2区医学

Glia Pub Date : 2024-06-19 DOI: 10.1002/glia.24568

Vasiliki-Ilya Gargareta, Stefan A. Berghoff, Doris Krauter, Sophie Hümmert, Katy L. H. Marshall-Phelps, Wiebke Möbius, Klaus-Armin Nave, Robert Fledrich, Hauke B. Werner, Maria A. Eichel-Vogel

{"title":"Myelinated peripheral axons are more vulnerable to mechanical trauma in a model of enlarged axonal diameters","authors":"Vasiliki-Ilya Gargareta, Stefan A. Berghoff, Doris Krauter, Sophie Hümmert, Katy L. H. Marshall-Phelps, Wiebke Möbius, Klaus-Armin Nave, Robert Fledrich, Hauke B. Werner, Maria A. Eichel-Vogel","doi":"10.1002/glia.24568","DOIUrl":"10.1002/glia.24568","url":null,"abstract":"The velocity of axonal impulse propagation is facilitated by myelination and axonal diameters. Both parameters are frequently impaired in peripheral nerve disorders, but it is not known if the diameters of myelinated axons affect the liability to injury or the efficiency of functional recovery. Mice lacking the adaxonal myelin protein chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6 (CMTM6) specifically from Schwann cells (SCs) display appropriate myelination but increased diameters of peripheral axons. Here we subjected Cmtm6-cKo mice as a model of enlarged axonal diameters to a mild sciatic nerve compression injury that causes temporarily reduced axonal diameters but otherwise comparatively moderate pathology of the axon/myelin-unit. Notably, both of these pathological features were worsened in Cmtm6-cKo compared to genotype-control mice early post-injury. The increase of axonal diameters caused by CMTM6-deficiency thus does not override their injury-dependent decrease. Accordingly, we did not detect signs of improved regeneration or functional recovery after nerve compression in Cmtm6-cKo mice; depleting CMTM6 in SCs is thus not a promising strategy toward enhanced recovery after nerve injury. Conversely, the exacerbated axonal damage in Cmtm6-cKo nerves early post-injury coincided with both enhanced immune response including foamy macrophages and SCs and transiently reduced grip strength. Our observations support the concept that larger peripheral axons are particularly susceptible toward mechanical trauma.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 9","pages":"1572-1589"},"PeriodicalIF":5.4,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24568","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416939","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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