Pub Date : 2018-08-16DOI: 10.3390/NEUROGLIA1010016
A. Chvátal, A. Verkhratsky
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.
{"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}
Pub Date : 2018-08-07DOI: 10.3390/NEUROGLIA1010015
M. Hayden, D. Grant, A. Aroor, V. DeMarco
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.
{"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}
Pub Date : 2018-07-17DOI: 10.3390/NEUROGLIA1010014
S. Herculano‐Houzel, S. D. Santos
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.
{"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}
Pub Date : 2018-07-17DOI: 10.3390/NEUROGLIA1010013
A. Verkhratsky, A. Butt
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.
{"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}
Pub Date : 2018-07-10DOI: 10.3390/NEUROGLIA1010012
C. Braskó, A. Butt
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.
{"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}
Pub Date : 2018-07-04DOI: 10.3390/NEUROGLIA1010010
I. Ferrer
Astrocytes are involved in many diseases of the central nervous system, not only as reactive cells to neuronal damage but also as primary actors in the pathological process. Astrogliopathy is a term used to designate the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Astrocytopathy is utilized to name non-reactive astrogliosis covering hypertrophy, atrophy and astroglial degeneration with loss of function in astrocytes and pathological remodeling, as well as senescent changes. Astrogliopathy and astrocytopathy are hallmarks of tauopathies—neurodegenerative diseases with abnormal hyper-phosphorylated tau aggregates in neurons and glial cells. The involvement of astrocytes covers different disease-specific types such as tufted astrocytes, astrocytic plaques, thorn-shaped astrocytes, granular/fuzzy astrocytes, ramified astrocytes and astrocytes with globular inclusions, as well as others which are unnamed but not uncommon in familial frontotemporal degeneration linked to mutations in the tau gene. Knowledge of molecular differences among tau-containing astrocytes is only beginning, and their distinct functional implications remain rather poorly understood. However, tau-containing astrocytes in certain conditions have deleterious effects on neuronal function and nervous system integrity. Moreover, recent studies have shown that tau-containing astrocytes obtained from human brain tauopathies have a capacity for abnormal tau seeding and spreading in wild type mice. Inclusive conceptions include a complex scenario involving neurons, glial cells and local environmental factors that potentiate each other and promote disease progression in tauopathies.
{"title":"Astrogliopathy in Tauopathies","authors":"I. Ferrer","doi":"10.3390/NEUROGLIA1010010","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010010","url":null,"abstract":"Astrocytes are involved in many diseases of the central nervous system, not only as reactive cells to neuronal damage but also as primary actors in the pathological process. Astrogliopathy is a term used to designate the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Astrocytopathy is utilized to name non-reactive astrogliosis covering hypertrophy, atrophy and astroglial degeneration with loss of function in astrocytes and pathological remodeling, as well as senescent changes. Astrogliopathy and astrocytopathy are hallmarks of tauopathies—neurodegenerative diseases with abnormal hyper-phosphorylated tau aggregates in neurons and glial cells. The involvement of astrocytes covers different disease-specific types such as tufted astrocytes, astrocytic plaques, thorn-shaped astrocytes, granular/fuzzy astrocytes, ramified astrocytes and astrocytes with globular inclusions, as well as others which are unnamed but not uncommon in familial frontotemporal degeneration linked to mutations in the tau gene. Knowledge of molecular differences among tau-containing astrocytes is only beginning, and their distinct functional implications remain rather poorly understood. However, tau-containing astrocytes in certain conditions have deleterious effects on neuronal function and nervous system integrity. Moreover, recent studies have shown that tau-containing astrocytes obtained from human brain tauopathies have a capacity for abnormal tau seeding and spreading in wild type mice. Inclusive conceptions include a complex scenario involving neurons, glial cells and local environmental factors that potentiate each other and promote disease progression in tauopathies.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45065565","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}
Pub Date : 2018-07-04DOI: 10.3390/NEUROGLIA1010011
Roberta Parolisi, E. Boda
Neuron-glia antigen 2-expressing glial cells (NG2 glia) serve as oligodendrocyte progenitors during development and adulthood. However, recent studies have shown that these cells represent not only a transitional stage along the oligodendroglial lineage, but also constitute a specific cell type endowed with typical properties and functions. Namely, NG2 glia (or subsets of NG2 glia) establish physical and functional interactions with neurons and other central nervous system (CNS) cell types, that allow them to constantly monitor the surrounding neuropil. In addition to operating as sensors, NG2 glia have features that are expected for active modulators of neuronal activity, including the expression and release of a battery of neuromodulatory and neuroprotective factors. Consistently, cell ablation strategies targeting NG2 glia demonstrate that, beyond their role in myelination, these cells contribute to CNS homeostasis and development. In this review, we summarize and discuss the advancements achieved over recent years toward the understanding of such functions, and propose novel approaches for further investigations aimed at elucidating the multifaceted roles of NG2 glia.
{"title":"NG2 Glia: Novel Roles beyond Re-/Myelination","authors":"Roberta Parolisi, E. Boda","doi":"10.3390/NEUROGLIA1010011","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010011","url":null,"abstract":"Neuron-glia antigen 2-expressing glial cells (NG2 glia) serve as oligodendrocyte progenitors during development and adulthood. However, recent studies have shown that these cells represent not only a transitional stage along the oligodendroglial lineage, but also constitute a specific cell type endowed with typical properties and functions. Namely, NG2 glia (or subsets of NG2 glia) establish physical and functional interactions with neurons and other central nervous system (CNS) cell types, that allow them to constantly monitor the surrounding neuropil. In addition to operating as sensors, NG2 glia have features that are expected for active modulators of neuronal activity, including the expression and release of a battery of neuromodulatory and neuroprotective factors. Consistently, cell ablation strategies targeting NG2 glia demonstrate that, beyond their role in myelination, these cells contribute to CNS homeostasis and development. In this review, we summarize and discuss the advancements achieved over recent years toward the understanding of such functions, and propose novel approaches for further investigations aimed at elucidating the multifaceted roles of NG2 glia.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42191698","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}
Pub Date : 2018-07-03DOI: 10.3390/NEUROGLIA1010009
Behrouz Moshrefi-Ravasdjani, Daniel Ziemens, N. Pape, Marcel Färfers, C. Rose
Recent work has established that glutamatergic synaptic activity induces transient sodium elevations in grey matter astrocytes by stimulating glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST). Glial sodium transients have diverse functional consequences but are largely unexplored in white matter. Here, we employed ratiometric imaging to analyse sodium signalling in macroglial cells of mouse corpus callosum. Electrical stimulation resulted in robust sodium transients in astrocytes, oligodendrocytes and NG2 glia, which were blocked by tetrodotoxin, demonstrating their dependence on axonal action potentials (APs). Action potential-induced sodium increases were strongly reduced by combined inhibition of ionotropic glutamate receptors and glutamate transporters, indicating that they are related to release of glutamate. While AMPA receptors were involved in sodium influx into all cell types, oligodendrocytes and NG2 glia showed an additional contribution of NMDA receptors. The transporter subtypes GLT-1 and GLAST were detected at the protein level and contributed to glutamate-induced glial sodium signals, indicating that both are functionally relevant for glutamate clearance in corpus callosum. In summary, our results demonstrate that white matter macroglial cells experience sodium influx through ionotropic glutamate receptors and glutamate uptake upon AP generation. Activity-induced glial sodium signalling may thus contribute to the communication between active axons and macroglial cells.
{"title":"Action Potential Firing Induces Sodium Transients in Macroglial Cells of the Mouse Corpus Callosum","authors":"Behrouz Moshrefi-Ravasdjani, Daniel Ziemens, N. Pape, Marcel Färfers, C. Rose","doi":"10.3390/NEUROGLIA1010009","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010009","url":null,"abstract":"Recent work has established that glutamatergic synaptic activity induces transient sodium elevations in grey matter astrocytes by stimulating glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST). Glial sodium transients have diverse functional consequences but are largely unexplored in white matter. Here, we employed ratiometric imaging to analyse sodium signalling in macroglial cells of mouse corpus callosum. Electrical stimulation resulted in robust sodium transients in astrocytes, oligodendrocytes and NG2 glia, which were blocked by tetrodotoxin, demonstrating their dependence on axonal action potentials (APs). Action potential-induced sodium increases were strongly reduced by combined inhibition of ionotropic glutamate receptors and glutamate transporters, indicating that they are related to release of glutamate. While AMPA receptors were involved in sodium influx into all cell types, oligodendrocytes and NG2 glia showed an additional contribution of NMDA receptors. The transporter subtypes GLT-1 and GLAST were detected at the protein level and contributed to glutamate-induced glial sodium signals, indicating that both are functionally relevant for glutamate clearance in corpus callosum. In summary, our results demonstrate that white matter macroglial cells experience sodium influx through ionotropic glutamate receptors and glutamate uptake upon AP generation. Activity-induced glial sodium signalling may thus contribute to the communication between active axons and macroglial cells.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43099283","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}
Pub Date : 2018-06-11DOI: 10.3390/NEUROGLIA1010007
Nicole Pukos, R. Yoseph, Dana M. McTigue
Oligodendrocytes are specialized glial cells that myelinate central nervous system (CNS) axons. Historically, it was believed that the primary role of myelin was to compactly ensheath axons, providing the insulation necessary for rapid signal conduction. However, mounting evidence demonstrates the dynamic importance of myelin and oligodendrocytes, including providing metabolic support to neurons and regulating axon protein distribution. As such, the development and maintenance of oligodendrocytes and myelin are integral to preserving CNS homeostasis and supporting proper functioning of widespread neural networks. Environmental signals are critical for proper oligodendrocyte lineage cell progression and their capacity to form functional compact myelin; these signals are markedly disturbed by injury to the CNS, which may compromise endogenous myelin repair capabilities. This review outlines some key environmental factors that drive myelin formation during development and compares that to the primary factors that define a CNS injury milieu. We aim to identify developmental factors disrupted after CNS trauma as well as pathogenic factors that negatively impact oligodendrocyte lineage cells, as these are potential therapeutic targets to promote myelin repair after injury or disease.
{"title":"To Be or Not to Be: Environmental Factors that Drive Myelin Formation during Development and after CNS Trauma","authors":"Nicole Pukos, R. Yoseph, Dana M. McTigue","doi":"10.3390/NEUROGLIA1010007","DOIUrl":"https://doi.org/10.3390/NEUROGLIA1010007","url":null,"abstract":"Oligodendrocytes are specialized glial cells that myelinate central nervous system (CNS) axons. Historically, it was believed that the primary role of myelin was to compactly ensheath axons, providing the insulation necessary for rapid signal conduction. However, mounting evidence demonstrates the dynamic importance of myelin and oligodendrocytes, including providing metabolic support to neurons and regulating axon protein distribution. As such, the development and maintenance of oligodendrocytes and myelin are integral to preserving CNS homeostasis and supporting proper functioning of widespread neural networks. Environmental signals are critical for proper oligodendrocyte lineage cell progression and their capacity to form functional compact myelin; these signals are markedly disturbed by injury to the CNS, which may compromise endogenous myelin repair capabilities. This review outlines some key environmental factors that drive myelin formation during development and compares that to the primary factors that define a CNS injury milieu. We aim to identify developmental factors disrupted after CNS trauma as well as pathogenic factors that negatively impact oligodendrocyte lineage cells, as these are potential therapeutic targets to promote myelin repair after injury or disease.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1010007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48360538","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}
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