Cells

Research

Jump to: Review

20 pages, 4802 KiB

Open AccessFeature PaperArticle

Neuron–Glia Interactions in Tuberous Sclerosis Complex Affect the Synaptic Balance in 2D and Organoid Cultures

by Stephanie Dooves, Arianne J. H. van Velthoven, Linda G. Suciati and Vivi M. Heine

Cells 2021, 10(1), 134; https://doi.org/10.3390/cells10010134 - 12 Jan 2021

Cited by 14 | Viewed by 3918

Abstract

Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance [...] Read more.

Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance (E/I balance) in TSC. Astrocytes are known to be important for neuronal development, and astrocytic dysfunction can cause changes in the E/I balance. We hypothesized that astrocytes affect the synaptic balance in TSC. TSC patient-derived stem cells were differentiated into astrocytes, which showed increased proliferation compared to control astrocytes. RNA sequencing revealed changes in gene expression, which were related to epidermal growth factor (EGF) signaling and enriched for genes that coded for secreted or transmembrane proteins. Control neurons were cultured in astrocyte-conditioned medium (ACM) of TSC and control astrocytes. After culture in TSC ACM, neurons showed an altered synaptic balance, with an increase in the percentage of VGAT⁺ synapses. These findings were confirmed in organoids, presenting a spontaneous 3D organization of neurons and glial cells. To conclude, this study shows that TSC astrocytes are affected and secrete factors that alter the synaptic balance. As an altered E/I balance may underlie many of the neurological TSC symptoms, astrocytes may provide new therapeutic targets. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

19 pages, 13916 KiB

Open AccessArticle

Rab6A as a Pan-Astrocytic Marker in Mouse and Human Brain, and Comparison with Other Glial Markers (GFAP, GS, Aldh1L1, SOX9)

by Linda Melzer, Thomas M. Freiman and Amin Derouiche

Cells 2021, 10(1), 72; https://doi.org/10.3390/cells10010072 - 05 Jan 2021

Cited by 5 | Viewed by 4933

Abstract

Astrocytes contribute to many higher brain functions. A key mechanism in glia-to-neuron signalling is vesicular exocytosis; however, the identity of exocytosis organelles remains a matter of debate. Since vesicles derived from the trans-Golgi network (TGN) are not considered in this context, we studied [...] Read more.

Astrocytes contribute to many higher brain functions. A key mechanism in glia-to-neuron signalling is vesicular exocytosis; however, the identity of exocytosis organelles remains a matter of debate. Since vesicles derived from the trans-Golgi network (TGN) are not considered in this context, we studied the astrocyte TGN by immunocytochemistry applying anti-Rab6A. In mouse brain, Rab6A immunostaining is found to be unexpectedly massive, diffuse in all regions, and is detected preferentially and abundantly in the peripheral astrocyte processes, which is hardly evident without glial fibrillary acid protein (GFAP) co-staining. All cells positive for the astrocytic markers glutamine synthetase (GS), GFAP, aldehyde dehydrogenase 1 family member L1 (Aldh1L1), or SRY (sex determining region Y)-box 9 (SOX9) were Rab6A⁺. Rab6A is excluded from microglia, oligodendrocytes, and NG2 cells using cell type-specific markers. In human cortex, Rab6A labelling is very similar and associated with GFAP⁺ astrocytes. The mouse data also confirm the specific astrocytic labelling by Aldh1L1 or SOX9; the astrocyte-specific labelling by GS sometimes debated is replicated again. In mouse and human brain, individual astrocytes display high variability in Rab6A⁺ structures, suggesting dynamic regulation of the glial TGN. In summary, Rab6A expression is an additional, global descriptor of astrocyte identity. Rab6A might constitute an organelle system with a potential role of Rab6A in neuropathological and physiological processes. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

20 pages, 3806 KiB

Open AccessArticle

Human Astrocytes Model Derived from Induced Pluripotent Stem Cells

by Nicolas Leventoux, Satoru Morimoto, Kent Imaizumi, Yuta Sato, Shinichi Takahashi, Kyoko Mashima, Mitsuru Ishikawa, Iki Sonn, Takahiro Kondo, Hirotaka Watanabe and Hideyuki Okano

Cells 2020, 9(12), 2680; https://doi.org/10.3390/cells9122680 - 13 Dec 2020

Cited by 31 | Viewed by 5985

Abstract

Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has [...] Read more.

Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has mainly focused on neurons because the protocols for generating astrocytes from iPSCs have not been fully established. The growing evidence of astrocytes’ contribution to neurodegenerative diseases has underscored the lack of iPSC-derived astrocyte models. In the present study, we established a protocol to efficiently generate iPSC-derived astrocytes (iPasts), which were further characterized by RNA and protein expression profiles as well as functional assays. iPasts exhibited calcium dynamics and glutamate uptake activity comparable to human primary astrocytes. Moreover, when co-cultured with neurons, iPasts enhanced neuronal synaptic maturation. Our protocol can be used for modeling astrocyte-related disease phenotypes in vitro and further exploring the contribution of astrocytes to neurodegenerative diseases. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

17 pages, 2241 KiB

Open AccessArticle

Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons

by Jessica Giacomoni, Andreas Bruzelius, Christina-Anastasia Stamouli and Daniella Rylander Ottosson

Cells 2020, 9(11), 2451; https://doi.org/10.3390/cells9112451 - 10 Nov 2020

Cited by 9 | Viewed by 4353

Abstract

Glial progenitor cells are widely distributed in brain parenchyma and represent a suitable target for future therapeutic interventions that generate new neurons via in situ reprogramming. Previous studies have shown successful reprogramming of mouse glia into neurons whereas the conversion of human glial [...] Read more.

Glial progenitor cells are widely distributed in brain parenchyma and represent a suitable target for future therapeutic interventions that generate new neurons via in situ reprogramming. Previous studies have shown successful reprogramming of mouse glia into neurons whereas the conversion of human glial cells remains challenging due to the limited accessibility of human brain tissue. Here, we have used a recently developed stem cell-based model of human glia progenitor cells (hGPCs) for direct neural reprogramming by overexpressing a set of transcription factors involved in GABAergic interneuron fate specification. GABAergic interneurons play a key role in balancing excitatory and inhibitory neural circuitry in the brain and loss or dysfunction of these have been implicated in several neurological disorders such as epilepsy, schizophrenia, and autism. Our results demonstrate that hGPCs successfully convert into functional induced neurons with postsynaptic activity within a month. The induced neurons have properties of GABAergic neurons, express subtype-specific interneuron markers (e.g. parvalbumin) and exhibit a complex neuronal morphology with extensive dendritic trees. The possibility of inducing GABAergic interneurons from a renewable in vitro hGPC system could provide a foundation for the development of therapies for interneuron pathologies. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

23 pages, 25341 KiB

Open AccessArticle

Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake

by Florent Guillebaud, Manon Barbot, Rym Barbouche, Jean-Michel Brézun, Kevin Poirot, Flora Vasile, Bruno Lebrun, Nathalie Rouach, Michel Dallaporta, Stéphanie Gaige and Jean-Denis Troadec

Cells 2020, 9(11), 2387; https://doi.org/10.3390/cells9112387 - 31 Oct 2020

Cited by 10 | Viewed by 3305

Abstract

The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located [...] Read more.

The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located in the hypothalamus and the dorsal vagal complex (DVC), which integrate nutritional, humoral and nervous information from the periphery. The glial cells’ contribution to these processes emerged few year ago. However, its underlying mechanism remains unclear. Glial connexin 43 hemichannels (Cx43 HCs) enable direct exchange with the extracellular space and can regulate neuronal network activity. In the present study, we sought to determine the possible involvement of glial Cx43 HCs in energy balance regulation. We here show that Cx43 is strongly expressed in the hypothalamus and DVC and is associated with glial cells. Remarkably, we observed a close apposition of Cx43 with synaptic elements in both the hypothalamus and DVC. Moreover, the expression of hypothalamic Cx43 mRNA and protein is modulated in response to fasting and diet-induced obesity. Functionally, we found that Cx43 HCs are largely open in the arcuate nucleus (ARC) from acute mice hypothalamic slices under basal condition, and significantly inhibited by TAT-GAP19, a mimetic peptide that specifically blocks Cx43 HCs activity. Moreover, intracerebroventricular (i.c.v.) TAT-GAP19 injection strongly decreased food intake, without further alteration of glycaemia, energy expenditures or locomotor activity. Using the immediate early gene c-Fos expression, we found that i.c.v. TAT-GAP19 injection induced neuronal activation in hypothalamic and brainstem nuclei dedicated to food intake regulation. Altogether, these results suggest a tonic delivery of orexigenic molecules associated with glial Cx43 HCs activity and a possible modulation of this tonus during fasting and obesity. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

16 pages, 3724 KiB

Open AccessArticle

Genetic Variation in CNS Myelination and Functional Brain Connectivity in Recombinant Inbred Mice

by Andrea Goudriaan, Maarten Loos, Sabine Spijker, August B. Smit and Mark H. G. Verheijen

Cells 2020, 9(9), 2119; https://doi.org/10.3390/cells9092119 - 18 Sep 2020

Cited by 4 | Viewed by 2243

Abstract

Myelination greatly increases the speed of action potential propagation of neurons, thereby enhancing the efficacy of inter-neuronal communication and hence, potentially, optimizing the brain’s signal processing capability. The impact of genetic variation on the extent of axonal myelination and its consequences for brain [...] Read more.

Myelination greatly increases the speed of action potential propagation of neurons, thereby enhancing the efficacy of inter-neuronal communication and hence, potentially, optimizing the brain’s signal processing capability. The impact of genetic variation on the extent of axonal myelination and its consequences for brain functioning remain to be determined. Here we investigated this question using a genetic reference panel (GRP) of mouse BXD recombinant inbred (RI) strains, which partly model genetic diversity as observed in human populations, and which show substantial genetic differences in a variety of behaviors, including learning, memory and anxiety. We found coherent differences in the expression of myelin genes in brain tissue of RI strains of the BXD panel, with the largest differences in the hippocampus. The parental C57BL/6J (C57) and DBA/2J (DBA) strains were on opposite ends of the expression spectrum, with C57 showing higher myelin transcript expression compared with DBA. Our experiments showed accompanying differences between C57 and DBA in myelin protein composition, total myelin content, and white matter conduction velocity. Finally, the hippocampal myelin gene expression of the BXD strains correlated significantly with behavioral traits involving anxiety and/or activity. Taken together, our data indicate that genetic variation in myelin gene expression translates to differences observed in myelination, axonal conduction speed, and possibly in anxiety/activity related behaviors. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

10 pages, 3855 KiB

Open AccessEditor’s ChoiceCommunication

Blocking Notch-Signaling Increases Neurogenesis in the Striatum after Stroke

by Giuseppe Santopolo, Jens P. Magnusson, Olle Lindvall, Zaal Kokaia and Jonas Frisén

Cells 2020, 9(7), 1732; https://doi.org/10.3390/cells9071732 - 20 Jul 2020

Cited by 26 | Viewed by 4313

Abstract

Stroke triggers neurogenesis in the striatum in mice, with new neurons deriving in part from the nearby subventricular zone and in part from parenchymal astrocytes. The initiation of neurogenesis by astrocytes within the striatum is triggered by reduced Notch-signaling, and blocking this signaling [...] Read more.

Stroke triggers neurogenesis in the striatum in mice, with new neurons deriving in part from the nearby subventricular zone and in part from parenchymal astrocytes. The initiation of neurogenesis by astrocytes within the striatum is triggered by reduced Notch-signaling, and blocking this signaling pathway by deletion of the gene encoding the obligate Notch coactivator Rbpj is sufficient to activate neurogenesis by striatal astrocytes in the absence of an injury. Here we report that blocking Notch-signaling in stroke increases the neurogenic response to stroke 3.5-fold in mice. Deletion of Rbpj results in the recruitment of a larger number of parenchymal astrocytes to neurogenesis and over larger areas of the striatum. These data suggest inhibition of Notch-signaling as a potential translational strategy to promote neuronal regeneration after stroke. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

12 pages, 1898 KiB

Open AccessArticle

Blocking Astrocytic GABA Restores Synaptic Plasticity in Prefrontal Cortex of Rat Model of Depression

by Ipsit Srivastava, Erika Vazquez-Juarez, Lukas Henning, Marta Gómez-Galán and Maria Lindskog

Cells 2020, 9(7), 1705; https://doi.org/10.3390/cells9071705 - 16 Jul 2020

Cited by 8 | Viewed by 3669

Abstract

A decrease in synaptic plasticity and/or a change in excitation/inhibition balance have been suggested as mechanisms underlying major depression disorder. However, given the crucial role of astrocytes in balancing synaptic function, particular attention should be given to the contribution of astrocytes in these [...] Read more.

A decrease in synaptic plasticity and/or a change in excitation/inhibition balance have been suggested as mechanisms underlying major depression disorder. However, given the crucial role of astrocytes in balancing synaptic function, particular attention should be given to the contribution of astrocytes in these mechanisms, especially since previous findings show that astrocytes are affected and exhibit reactive-like features in depression. Moreover, it has been shown that reactive astrocytes increase the synthesis and release of GABA, contributing significantly to tonic GABA inhibition. In this study we found decreased plasticity and increased tonic GABA inhibition in the prelimbic area in acute slices from the medial prefrontal cortex in the Flinders Sensitive Line (FSL) rat model of depression. The tonic inhibition can be reduced by either blocking astrocytic intracellular Ca²⁺ signaling or by reducing astrocytic GABA through inhibition of the synthesizing enzyme MAO-B with Selegiline. Blocking GABA synthesis also restores the impaired synaptic plasticity in the FSL prefrontal cortex, providing a new antidepressant mechanism of Selegiline. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

18 pages, 2174 KiB

Open AccessArticle

Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models

by James A. Gregory, Emily Hoelzli, Rawan Abdelaal, Catherine Braine, Miguel Cuevas, Madeline Halpern, Natalie Barretto, Nadine Schrode, Güney Akbalik, Kristy Kang, Esther Cheng, Kathryn Bowles, Steven Lotz, Susan Goderie, Celeste M. Karch, Sally Temple, Alison Goate, Kristen J. Brennand and Hemali Phatnani

Cells 2020, 9(6), 1406; https://doi.org/10.3390/cells9061406 - 05 Jun 2020

Cited by 3 | Viewed by 5578

Abstract

Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to [...] Read more.

Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to resolve cell type-specific perturbations. Here, we report an extension of the RiboTag system, first developed to achieve cell type-restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables depletion of up to 87 percent of off-target RNA in mixed species co-cultures. Nonetheless, depletion efficiency varies across independent experimental replicates, particularly for hiPSC-derived motor neurons. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

Review

Jump to: Research

33 pages, 1186 KiB

Open AccessReview

Using iPSC Models to Understand the Role of Estrogen in Neuron–Glia Interactions in Schizophrenia and Bipolar Disorder

by Denis Reis de Assis, Attila Szabo, Jordi Requena Osete, Francesca Puppo, Kevin S. O’Connell, Ibrahim A. Akkouh, Timothy Hughes, Evgeniia Frei, Ole A. Andreassen and Srdjan Djurovic

Cells 2021, 10(2), 209; https://doi.org/10.3390/cells10020209 - 21 Jan 2021

Cited by 8 | Viewed by 5656

Abstract

Schizophrenia (SCZ) and bipolar disorder (BIP) are severe mental disorders with a considerable disease burden worldwide due to early age of onset, chronicity, and lack of efficient treatments or prevention strategies. Whilst our current knowledge is that SCZ and BIP are highly heritable [...] Read more.

Schizophrenia (SCZ) and bipolar disorder (BIP) are severe mental disorders with a considerable disease burden worldwide due to early age of onset, chronicity, and lack of efficient treatments or prevention strategies. Whilst our current knowledge is that SCZ and BIP are highly heritable and share common pathophysiological mechanisms associated with cellular signaling, neurotransmission, energy metabolism, and neuroinflammation, the development of novel therapies has been hampered by the unavailability of appropriate models to identify novel targetable pathomechanisms. Recent data suggest that neuron–glia interactions are disturbed in SCZ and BIP, and are modulated by estrogen (E2). However, most of the knowledge we have so far on the neuromodulatory effects of E2 came from studies on animal models and human cell lines, and may not accurately reflect many processes occurring exclusively in the human brain. Thus, here we highlight the advantages of using induced pluripotent stem cell (iPSC) models to revisit studies of mechanisms underlying beneficial effects of E2 in human brain cells. A better understanding of these mechanisms opens the opportunity to identify putative targets of novel therapeutic agents for SCZ and BIP. In this review, we first summarize the literature on the molecular mechanisms involved in SCZ and BIP pathology and the beneficial effects of E2 on neuron–glia interactions. Then, we briefly present the most recent developments in the iPSC field, emphasizing the potential of using patient-derived iPSCs as more relevant models to study the effects of E2 on neuron–glia interactions. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

20 pages, 2072 KiB

Open AccessReview

Neuron–Glia Interaction in the Developing and Adult Enteric Nervous System

by Verena Pawolski and Mirko H. H. Schmidt

Cells 2021, 10(1), 47; https://doi.org/10.3390/cells10010047 - 31 Dec 2020

Cited by 23 | Viewed by 7571

Abstract

The enteric nervous system (ENS) constitutes the largest part of the peripheral nervous system. In recent years, ENS development and its neurogenetic capacity in homeostasis and allostasishave gained increasing attention. Developmentally, the neural precursors of the ENS are mainly derived from vagal and [...] Read more.

The enteric nervous system (ENS) constitutes the largest part of the peripheral nervous system. In recent years, ENS development and its neurogenetic capacity in homeostasis and allostasishave gained increasing attention. Developmentally, the neural precursors of the ENS are mainly derived from vagal and sacral neural crest cell portions. Furthermore, Schwann cell precursors, as well as endodermal pancreatic progenitors, participate in ENS formation. Neural precursors enherite three subpopulations: a bipotent neuron-glia, a neuronal-fated and a glial-fated subpopulation. Typically, enteric neural precursors migrate along the entire bowel to the anal end, chemoattracted by glial cell-derived neurotrophic factor (GDNF) and endothelin 3 (EDN3) molecules. During migration, a fraction undergoes differentiation into neurons and glial cells. Differentiation is regulated by bone morphogenetic proteins (BMP), Hedgehog and Notch signalling. The fully formed adult ENS may react to injury and damage with neurogenesis and gliogenesis. Nevertheless, the origin of differentiating cells is currently under debate. Putative candidates are an embryonic-like enteric neural progenitor population, Schwann cell precursors and transdifferentiating glial cells. These cells can be isolated and propagated in culture as adult ENS progenitors and may be used for cell transplantation therapies for treating enteric aganglionosis in Chagas and Hirschsprung’s diseases. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

28 pages, 1349 KiB

Open AccessReview

Neuron-Astrocyte Interactions in Parkinson’s Disease

by Ikuko Miyazaki and Masato Asanuma

Cells 2020, 9(12), 2623; https://doi.org/10.3390/cells9122623 - 07 Dec 2020

Cited by 82 | Viewed by 10135

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Graphical abstract

33 pages, 1545 KiB

Open AccessFeature PaperReview

An Overview of Astrocyte Responses in Genetically Induced Alzheimer’s Disease Mouse Models

by Fokion Spanos and Shane A. Liddelow

Cells 2020, 9(11), 2415; https://doi.org/10.3390/cells9112415 - 04 Nov 2020

Cited by 18 | Viewed by 9751

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. Despite many years of intense research, there is currently still no effective treatment. Multiple cell types contribute to disease pathogenesis, with an increasing body of data pointing to the active participation of astrocytes. [...] Read more.

Alzheimer’s disease (AD) is the most common form of dementia. Despite many years of intense research, there is currently still no effective treatment. Multiple cell types contribute to disease pathogenesis, with an increasing body of data pointing to the active participation of astrocytes. Astrocytes play a pivotal role in the physiology and metabolic functions of neurons and other cells in the central nervous system. Because of their interactions with other cell types, astrocyte functions must be understood in their biologic context, thus many studies have used mouse models, of which there are over 190 available for AD research. However, none appear able to fully recapitulate the many functional changes in astrocytes reported in human AD brains. Our review summarizes the observations of astrocyte biology noted in mouse models of familial and sporadic AD. The limitations of AD mouse models will be discussed and current attempts to overcome these disadvantages will be described. With increasing understanding of the non-neuronal contributions to disease, the development of new methods and models will provide further insights and address important questions regarding the roles of astrocytes and other non-neuronal cells in AD pathophysiology. The next decade will prove to be full of exciting opportunities to address this devastating disease. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

21 pages, 1502 KiB

Open AccessEditor’s ChoiceReview

Neuron-Glia Interactions in Neurodevelopmental Disorders

by Yoo Sung Kim, Juwon Choi and Bo-Eun Yoon

Cells 2020, 9(10), 2176; https://doi.org/10.3390/cells9102176 - 27 Sep 2020

Cited by 65 | Viewed by 9910

Abstract

Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity. Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological function of [...] Read more.

Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity. Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological function of the central nervous system (CNS). In particular, glial cells undergo gliotransmission and regulate neuronal activity in tripartite synapses via ion channels (gap junction hemichannel, volume regulated anion channel, and bestrophin-1), receptors (for neurotransmitters and cytokines), or transporters (GLT-1, GLAST, and GATs) that are expressed on glial cell membranes. In this review, we propose that dysfunction in neuron-glia interactions may contribute to the pathogenesis of neurodevelopmental disorders. Understanding the mechanisms of neuron-glia interaction for synapse formation and maturation will contribute to the development of novel therapeutic targets of neurodevelopmental disorders. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

21 pages, 2507 KiB

Open AccessReview

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

by Naoki Abe, Tasuku Nishihara, Toshihiro Yorozuya and Junya Tanaka

Cells 2020, 9(9), 2132; https://doi.org/10.3390/cells9092132 - 21 Sep 2020

Cited by 47 | Viewed by 7203

Abstract

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. [...] Read more.

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes. Full article

(This article belongs to the Special Issue Neuron-Glia Interactions)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Neuron-Glia Interactions

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (15 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI