Neuroglia (Basel, Switzerland)最新文献_第5页

In Search of a Breakthrough Therapy for Glioblastoma Multiforme 寻求突破性治疗多型胶质母细胞瘤

Neuroglia (Basel, Switzerland) Pub Date : 2018-09-26 DOI: 10.3390/NEUROGLIA1020020

A. Vasilev, Roba Sofi, L. Tong, A. Teschemacher, S. Kasparov

{"title":"In Search of a Breakthrough Therapy for Glioblastoma Multiforme","authors":"A. Vasilev, Roba Sofi, L. Tong, A. Teschemacher, S. Kasparov","doi":"10.3390/NEUROGLIA1020020","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1020020","url":null,"abstract":"Glioblastoma multiforme (GBM) is an extremely malignant type of brain cancer which originates from astrocytes or their precursors. Glioblastoma multiforme cells share some features with astrocytes but are characterized by highly unstable genomes with multiple driver mutations and aberrations. Effective therapies for GBM are lacking and hardly any progress has been made in the last 15 years in terms of improving the outcomes for patients. The lack of new especially targeted anti-GBM medications has prompted scientists in academia around the world to test whether any of the currently approved drugs might be used to fight this devastating disease. This approach is known as repurposing. Dozens of drugs have been reported to have anti-GBM properties in vitro but there is no solid evidence for the clinical efficacy of any of them. Perhaps the most interesting group of those repurposed are tricyclic antidepressants but the mechanism of their action on GBM cells remains obscure. In this brief review we consider various approaches to repurpose drugs for therapy of GBM and highlight their limitations. We also pay special attention to the mitochondria, which appear to be intimately involved in the process of apoptosis and could be a focus of future developments in search of a better treatment for patients suffering from GBM.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1020020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45648973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Mediation of FoxO1 in Activated Neuroglia Deficient for Nucleoside Diphosphate Kinase B during Vascular Degeneration fox01在血管变性过程中核苷二磷酸激酶B缺陷激活的神经胶质细胞中的介导作用

Neuroglia (Basel, Switzerland) Pub Date : 2018-09-07 DOI: 10.3390/neuroglia1010019

Y. Qiu, Hongpeng Huang, Anupriya Chatterjee, L. Teuma, F. Baumann, H. Hammes, T. Wieland, Yuxi Feng

{"title":"Mediation of FoxO1 in Activated Neuroglia Deficient for Nucleoside Diphosphate Kinase B during Vascular Degeneration","authors":"Y. Qiu, Hongpeng Huang, Anupriya Chatterjee, L. Teuma, F. Baumann, H. Hammes, T. Wieland, Yuxi Feng","doi":"10.3390/neuroglia1010019","DOIUrl":"https://doi.org/10.3390/neuroglia1010019","url":null,"abstract":"The pathogenesis of diabetic retinopathy is closely associated with the breakdown of the neurovascular unit including the glial cells. Deficiency of nucleoside diphosphate kinase B (NDPK-B) results in retinal vasoregression mimicking diabetic retinopathy. Increased retinal expression of Angiopoietin-2 (Ang-2) initiates vasoregression. In this study, Müller cell activation, glial Ang-2 expression, and the underlying mechanisms were investigated in streptozotocin-induced diabetic NDPK-B deficient (KO) retinas and Müller cells isolated from the NDPK-B KO retinas. Müller cells were activated and Ang-2 expression was predominantly increased in Müller cells in normoglycemic NDPK-B KO retinas, similar to diabetic wild type (WT) retinas. Diabetes induction in the NDPK-B KO mice did not further increase its activation. Additionally, cultured NDPK-B KO Müller cells were more activated and showed higher Ang-2 expression than WT cells. Müller cell activation and Ang-2 elevation were observed upon high glucose treatment in WT, but not in NDPK-B KO cells. Moreover, increased levels of the transcription factor forkhead box protein O1 (FoxO1) were detected in non-diabetic NDPK-B KO Müller cells. The siRNA-mediated knockdown of FoxO1 in NDPK-B deficient cells interfered with Ang-2 upregulation. These data suggest that FoxO1 mediates Ang-2 upregulation induced by NDPK-B deficiency in the Müller cells and thus contributes to the onset of retinal vascular degeneration.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/neuroglia1010019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48903723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Sequential Contribution of Parenchymal and Neural Stem Cell-Derived Oligodendrocyte Precursor Cells toward Remyelination. 实质细胞和神经干细胞衍生的少突胶质前体细胞对再髓鞘化的相继贡献

Neuroglia (Basel, Switzerland) Pub Date : 2018-09-01 Epub Date: 2018-06-12 DOI: 10.3390/neuroglia1010008

David R Serwanski, Andrew L Rasmussen, Christopher B Brunquell, Scott S Perkins, Akiko Nishiyama

{"title":"Sequential Contribution of Parenchymal and Neural Stem Cell-Derived Oligodendrocyte Precursor Cells toward Remyelination.","authors":"David R Serwanski, Andrew L Rasmussen, Christopher B Brunquell, Scott S Perkins, Akiko Nishiyama","doi":"10.3390/neuroglia1010008","DOIUrl":"10.3390/neuroglia1010008","url":null,"abstract":"<p><p>In the adult mammalian forebrain, oligodendrocyte precursor cells (OPCs), also known as NG2 glia are distributed ubiquitously throughout the gray and white matter. They remain proliferative and continuously generate myelinating oligodendrocytes throughout life. In response to a demyelinating insult, OPCs proliferate rapidly and differentiate into oligodendrocytes which contribute to myelin repair. In addition to OPCs, neural stem cells (NSCs) in the subventricular zone (SVZ) also contribute to remyelinating oligodendrocytes, particularly in demyelinated lesions in the vicinity of the SVZ, such as the corpus callosum. To determine the relative contribution of local OPCs and NSC-derived cells toward myelin repair, we performed genetic fate mapping of OPCs and NSCs and compared their ability to generate oligodendrocytes after acute demyelination in the corpus callosum created by local injection of α-lysophosphatidylcholine (LPC). We have found that local OPCs responded rapidly to acute demyelination, expanded in the lesion within seven days, and produced oligodendrocytes by two weeks after lesioning. By contrast, NSC-derived NG2 cells did not significantly increase in the lesion until four weeks after demyelination and generated fewer oligodendrocytes than parenchymal OPCs. These observations suggest that local OPCs could function as the primary responders to repair acutely demyelinated lesion, and that NSCs in the SVZ contribute to repopulating OPCs following their depletion due to oligodendrocyte differentiation.</p>","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"1 1","pages":"91-105"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36881560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Syncytial Isopotentiality: An Electrical Feature of Spinal Cord Astrocyte Networks 合胞体等电位：脊髓星形细胞网络的电学特征

Neuroglia (Basel, Switzerland) Pub Date : 2018-08-24 DOI: 10.3390/NEUROGLIA1010018

M. Huang, Yixing Du, Conrad M. Kiyoshi, Xiao Wu, C. Askwith, D. McTigue, Min Zhou

{"title":"Syncytial Isopotentiality: An Electrical Feature of Spinal Cord Astrocyte Networks","authors":"M. Huang, Yixing Du, Conrad M. Kiyoshi, Xiao Wu, C. Askwith, D. McTigue, Min Zhou","doi":"10.3390/NEUROGLIA1010018","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010018","url":null,"abstract":"Due to strong electrical coupling, syncytial isopotentiality emerges as a physiological mechanism that coordinates astrocytes into a highly efficient system in brain homeostasis. Although this electrophysiological phenomenon has now been observed in astrocyte networks established by different astrocyte subtypes, the spinal cord remains a brain region that is still unexplored. In ALDH1L1-eGFP transgenic mice, astrocytes can be visualized by confocal microscopy and the spinal cord astrocytes in grey matter are organized in a distinctive pattern. Namely, each astrocyte resides with more directly coupled neighbors at shorter interastrocytic distances compared to protoplasmic astrocytes in the hippocampal CA1 region. In whole-cell patch clamp recording, the spinal cord grey matter astrocytes exhibit passive K+ conductance and a highly hyperpolarized membrane potential of −80 mV. To answer whether syncytial isopotentiality is a shared feature of astrocyte networks in the spinal cord, the K+ content in a physiological recording solution was substituted by equimolar Na+ for whole-cell recording in spinal cord slices. In uncoupled single astrocytes, this substitution of endogenous K+ with Na+ is known to depolarize astrocytes to around 0 mV as predicted by Goldman–Hodgkin–Katz (GHK) equation. In contrast, the existence of syncytial isopotentiality is indicated by a disobedience of the GHK predication as the recorded astrocyte’s membrane potential remains at a quasi-physiological level that is comparable to its neighbors due to strong electrical coupling. We showed that the strength of syncytial isopotentiality in spinal cord grey matter is significantly stronger than that of astrocyte network in the hippocampal CA1 region. Thus, this study corroborates the notion that syncytial isopotentiality most likely represents a system-wide electrical feature of astrocytic networks throughout the brain.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43623804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone 炎症细胞因子促进P2X7受体对啮齿动物海马亚颗粒区神经祖细胞细胞外ATP的敏感性

Neuroglia (Basel, Switzerland) Pub Date : 2018-08-22 DOI: 10.3390/NEUROGLIA1010017

Juan Liu, M. T. Khan, Yong Tang, H. Franke, P. Illés

{"title":"Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone","authors":"Juan Liu, M. T. Khan, Yong Tang, H. Franke, P. Illés","doi":"10.3390/NEUROGLIA1010017","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010017","url":null,"abstract":"Organotypic hippocampal slice cultures were used to model the effects of neuroinflammatory conditions following an epileptic state on functional P2X7 receptors (Rs) of subgranular zone (SGZ) neural progenitor cells (NPCs). The compound, 4-aminopyridine (4-AP), is known to cause pathological firing of neurons, consequently facilitating the release of various transmitter substances including ATP. Lipopolysaccharide (LPS) and interleukin-1β (IL-1β) both potentiated the dibenzoyl-ATP (Bz-ATP)-induced current amplitudes in NPCs, although via different mechanisms. Whereas LPS acted via promoting ATP release, IL-1β acted via its own receptor to directly influence P2X7Rs. Thus, the effect of LPS was inhibited by the ecto-ATPase inhibitor, apyrase, but not by the IL-1β antagonist, interleukin-1RA (IL-1RA); by contrast, the effect of IL-1β was inhibited by IL-1RA, but not by apyrase. Eventually, incubation with 4-AP upregulated the number of nestin/glial fibrillary acidic protein/P2X7R immunoreactive cells and their appropriate staining intensity, suggesting increased synthesis of P2X7Rs at NPCs. In conclusion, inflammatory cytokines accumulating after epilepsy-like neuronal firing may facilitate the effect of endogenous ATP at P2X7Rs of NPCs, thereby probably promoting necrosis/apoptosis and subsequent cell death.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41626685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Early History of Neuroglial Research: Personalities 神经胶质研究的早期历史:人格

Neuroglia (Basel, Switzerland) Pub Date : 2018-08-16 DOI: 10.3390/NEUROGLIA1010016

A. Chvátal, A. Verkhratsky

{"title":"An Early History of Neuroglial Research: Personalities","authors":"A. Chvátal, A. Verkhratsky","doi":"10.3390/NEUROGLIA1010016","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010016","url":null,"abstract":"Neuroscience, like most other divisions of natural philosophy, emerged in the Hellenistic world following the first experimental discoveries of the nerves connecting the brain with the body. The first fundamental doctrine on brain function highlighted the role for a specific substance, pneuma, which appeared as a substrate for brain function and, being transported through the hollow nerves, operated the peripheral organs. A paradigm shift occurred in 17th century when brain function was relocated to the grey matter. Beginning from the end of the 18th century, the existence of active and passive portions of the nervous tissue were postulated. The passive part of the nervous tissue has been further conceptualised by Rudolf Virchow, who introduced the notion of neuroglia as a connective tissue of the brain and the spinal cord. During the second half of the 19th century, the cellular architecture of the brain was been extensively studied, which led to an in-depth morphological characterisation of multiple cell types, including a detailed description of the neuroglia. Here, we present the views and discoveries of the main personalities of early neuroglial research.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69757925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part I: Astrocyte 女性糖尿病db/db模型中神经血管单元的超微结构重塑-第一部分:星形胶质细胞

Neuroglia (Basel, Switzerland) Pub Date : 2018-08-07 DOI: 10.3390/NEUROGLIA1010015

M. Hayden, D. Grant, A. Aroor, V. DeMarco

{"title":"Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part I: Astrocyte","authors":"M. Hayden, D. Grant, A. Aroor, V. DeMarco","doi":"10.3390/NEUROGLIA1010015","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010015","url":null,"abstract":"Obesity, insulin resistance, and type 2 diabetes mellitus are associated with cognitive impairment, known as diabetic cognopathy. In this study, we tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions display abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db (BKS.CgDock7m +/+Leprdb/J; DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (at 20 weeks of age), left-brain hemispheres of the DBC and age-matched non-diabetic wild-type control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We found attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickening of the basement membrane, aberrant mitochondria, and pathological remodeling of protoplasmic astrocytes. Additionally, there were adherent red blood cells and NVU microbleeds (cortical layer III) in DBC mice, which were not observed in CKC animals. While this study represents only a “snapshot in time”, it does allow for cellular remodeling comparisons between DBC and CKC. In this paper, the first of a three-part series, we report the observational ultrastructural remodeling changes of the NVU and its protoplasmic astrocytes in relation to the surrounding neuropil. Having identified multiple abnormal cellular remodeling changes in the DBC as compared to CKC models, we will design future experiments to evaluate various treatment modalities in DBC mice.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48504464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

You Do Not Mess with the Glia 你不要惹Glia

Neuroglia (Basel, Switzerland) Pub Date : 2018-07-17 DOI: 10.3390/NEUROGLIA1010014

S. Herculano‐Houzel, S. D. Santos

{"title":"You Do Not Mess with the Glia","authors":"S. Herculano‐Houzel, S. D. Santos","doi":"10.3390/NEUROGLIA1010014","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010014","url":null,"abstract":"Vertebrate neurons are enormously variable in morphology and distribution. While different glial cell types do exist, they are much less diverse than neurons. Over the last decade, we have conducted quantitative studies of the absolute numbers, densities, and proportions at which non-neuronal cells occur in relation to neurons. These studies have advanced the notion that glial cells are much more constrained than neurons in how much they can vary in both development and evolution. Recent evidence from studies on gene expression profiles that characterize glial cells—in the context of progressive epigenetic changes in chromatin during morphogenesis—supports the notion of constrained variation of glial cells in development and evolution, and points to the possibility that this constraint is related to the late differentiation of the various glial cell types. Whether restricted variation is a biological given (a simple consequence of late glial cell differentiation) or a physiological constraint (because, well, you do not mess with the glia without consequences that compromise brain function to the point of rendering those changes unviable), we predict that the restricted variation in size and distribution of glial cells has important consequences for neural tissue function that is aligned with their many fundamental roles being uncovered.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44167687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

The History of the Decline and Fall of the Glial Numbers Legend 神经胶质细胞数目传奇的衰亡史

Neuroglia (Basel, Switzerland) Pub Date : 2018-07-17 DOI: 10.3390/NEUROGLIA1010013

A. Verkhratsky, A. Butt

{"title":"The History of the Decline and Fall of the Glial Numbers Legend","authors":"A. Verkhratsky, A. Butt","doi":"10.3390/NEUROGLIA1010013","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010013","url":null,"abstract":"In the field of neuroscience and, more specifically glial cell biology, one of the most fundamentally intriguing and enduring questions has been “how many neuronal cells—neurones and glia—are there in the human brain?”. From the outset, the driving force behind this question was undoubtedly the scientific quest for knowledge of why humans are more intelligent than even our nearest relatives; the ‘neuronal doctrine’ dictated we must have more neurones than other animals. The early histological studies indicated a vast space between neurones that was filled by ‘nervenkitt’, later identified as neuroglia; arguably, this was the origin of the myth that glia massively outnumber neurones in the human brain. The myth eventually became embedded in ideology when later studies seemed to confirm that glia outnumber neurones in the human cortex—the seat of humanity—and that there was an inevitable rise in the glia-to-neurone ratio (GNR) as we climbed the evolutionary tree. This could be described as the ‘glial doctrine’—that the rise of intelligence and the rise of glia go hand-in-hand. In many ways, the GNR became a mantra for working on glial cells at a time when the neuronal doctrine ruled the world. However, the work of Suzana Herculano-Houzel which she reviews in this first volume of Neuroglia has led the way in demonstrating that neurones and glia are almost equal in number in the human cortex and there is no inexorable phylogenetic rise in the GNR. In this commentary we chart the fall and decline of the mythology of the GNR.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46615079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Expression of Kir2.1 Inward Rectifying Potassium Channels in Optic Nerve Glia: Evidence for Heteromeric Association with Kir4.1 and Kir5.1 Kir2.1向内纠偏钾通道在视神经胶质中的表达:与Kir4.1和Kir5.1异聚相关的证据

Neuroglia (Basel, Switzerland) Pub Date : 2018-07-10 DOI: 10.3390/NEUROGLIA1010012

C. Braskó, A. Butt

{"title":"Expression of Kir2.1 Inward Rectifying Potassium Channels in Optic Nerve Glia: Evidence for Heteromeric Association with Kir4.1 and Kir5.1","authors":"C. Braskó, A. Butt","doi":"10.3390/NEUROGLIA1010012","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010012","url":null,"abstract":"Inward rectifying potassium (Kir) channels comprise a large family with diverse biophysical properties. A predominant feature of central nervous system (CNS) glia is their expression of Kir4.1, which as homomers are weakly rectifying channels, but form strongly rectifying channels as heteromers with Kir2.1. However, the extent of Kir2.1 expression and their association with Kir4.1 in glia throughout the CNS is unclear. We have examined this in astrocytes and oligodendrocytes of the mouse optic nerve, a typical CNS white matter tract. Western blot and immunocytochemistry demonstrates that optic nerve astrocytes and oligodendrocytes express Kir2.1 and that it co-localises with Kir4.1. Co-immunoprecipitation analysis provided further evidence that Kir2.1 associate with Kir4.1 and, moreover, Kir2.1 expression was significantly reduced in optic nerves and brains from Kir4.1 knock-out mice. In addition, optic nerve glia express Kir5.1, which may associate with Kir2.1 to form silent channels. Immunocytochemical and co-immunoprecipitation analyses indicate that Kir2.1 associate with Kir5.1 in optic nerve glia, but not in the brain. The results provide evidence that astrocytes and oligodendrocytes may express heteromeric Kir2.1/Kir4.1 and Kir2.1/Kir5.1 channels, together with homomeric Kir2.1 and Kir4.1 channels. In astrocytes, expression of multiple Kir channels is the biophysical substrate for the uptake and redistribution of K+ released during neuronal electrical activity known as ‘potassium spatial buffering’. Our findings suggest a similar potential role for the diverse Kir channels expressed by oligodendrocytes, which by way of their myelin sheaths are intimately associated with the sites of action potential propagation and axonal K+ release.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48291244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6