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Cells Sep 2020Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development,... (Review)
Review
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.
Topics: Astrocytes; Homeostasis; Humans; Neurodevelopmental Disorders; Neurogenesis; Neuroglia; Neurons
PubMed: 32992620
DOI: 10.3390/cells9102176 -
Nature Neuroscience Feb 2016The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led... (Review)
Review
The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function.
Topics: Animals; Astrocytes; Calcium Signaling; Humans; Neuroglia; Neurotransmitter Agents
PubMed: 26814587
DOI: 10.1038/nn.4201 -
Trends in Neurosciences Mar 2020Healthy central nervous system (CNS) development and function require an intricate and balanced bidirectional communication between neurons and glia cells. In this... (Review)
Review
Healthy central nervous system (CNS) development and function require an intricate and balanced bidirectional communication between neurons and glia cells. In this review, we discuss the complementary roles of astrocytes and microglia in building the brain, including in the formation and refinement of synapses. We discuss recent evidence demonstrating how these interactions are coordinated in the transition from healthy physiology towards disease and discuss known and potential molecular mechanisms that mediate this cellular crosstalk.
Topics: Astrocytes; Humans; Microglia; Neuroglia; Neurons; Synapses
PubMed: 32044129
DOI: 10.1016/j.tins.2020.01.003 -
Nature Reviews. Neuroscience Nov 2019Astrocytes are critical for maintaining the homeostasis of the CNS. Increasing evidence suggests that a number of neurological and neuropsychiatric disorders, including... (Review)
Review
Astrocytes are critical for maintaining the homeostasis of the CNS. Increasing evidence suggests that a number of neurological and neuropsychiatric disorders, including chronic pain, may result from astrocyte 'gliopathy'. Indeed, in recent years there has been substantial progress in our understanding of how astrocytes can regulate nociceptive synaptic transmission via neuronal-glial and glial-glial cell interactions, as well as the involvement of spinal and supraspinal astrocytes in the modulation of pain signalling and the maintenance of neuropathic pain. A role of astrocytes in the pathogenesis of chronic itch is also emerging. These developments suggest that targeting the specific pathways that are responsible for astrogliopathy may represent a novel approach to develop therapies for chronic pain and chronic itch.
Topics: Animals; Astrocytes; Cell Communication; Chronic Pain; Homeostasis; Humans; Neuroglia; Pruritus; Synapses
PubMed: 31537912
DOI: 10.1038/s41583-019-0218-1 -
Nature Reviews. Neuroscience Jul 2014Müller glia are the major glial component of the retina. They are one of the last retinal cell types to be born during development, and they function to maintain... (Review)
Review
Müller glia are the major glial component of the retina. They are one of the last retinal cell types to be born during development, and they function to maintain retinal homeostasis and integrity. In mammals, Müller glia respond to retinal injury in various ways that can be either protective or detrimental to retinal function. Although these cells can be coaxed to proliferate and generate neurons under special circumstances, these responses are meagre and insufficient for repairing a damaged retina. By contrast, in teleost fish (such as zebrafish), the response of Müller glia to retinal injury involves a reprogramming event that imparts retinal stem cell characteristics and enables them to produce a proliferating population of progenitors that can regenerate all major retinal cell types and restore vision. Recent studies have revealed several important mechanisms underlying Müller glial cell reprogramming and retina regeneration in fish that may lead to new strategies for stimulating retina regeneration in mammals.
Topics: Animals; Ependymoglial Cells; Humans; Nerve Net; Nerve Regeneration; Neuroglia; Retina; Signal Transduction
PubMed: 24894585
DOI: 10.1038/nrn3723 -
Neuron Mar 2019We define the chemoconnectome (CCT) as the entire set of neurotransmitters, neuromodulators, neuropeptides, and their receptors underlying chemotransmission in an...
We define the chemoconnectome (CCT) as the entire set of neurotransmitters, neuromodulators, neuropeptides, and their receptors underlying chemotransmission in an animal. We have generated knockout lines of Drosophila CCT genes for functional investigations and knockin lines containing Gal4 and other tools for examining gene expression and manipulating neuronal activities, with a versatile platform allowing genetic intersections and logic gates. CCT reveals the coexistence of specific transmitters but mutual exclusion of the major inhibitory and excitatory transmitters in the same neurons. One neuropeptide and five receptors were detected in glia, with octopamine β2 receptor functioning in glia. A pilot screen implicated 41 genes in sleep regulation, with the dopamine receptor Dop2R functioning in neurons expressing the peptides Dilp2 and SIFa. Thus, CCT is a novel concept, chemoconnectomics a new approach, and CCT tool lines a powerful resource for systematic investigations of chemical-transmission-mediated neural signaling circuits underlying behavior and cognition.
Topics: Animals; Connectome; Drosophila melanogaster; Neuroglia; Neurons; Neurotransmitter Agents; Synaptic Transmission
PubMed: 30799021
DOI: 10.1016/j.neuron.2019.01.045 -
Nature Reviews. Gastroenterology &... Aug 2021One of the most transformative developments in neurogastroenterology is the realization that many functions normally attributed to enteric neurons involve interactions... (Review)
Review
One of the most transformative developments in neurogastroenterology is the realization that many functions normally attributed to enteric neurons involve interactions with enteric glial cells: a large population of peripheral neuroglia associated with enteric neurons throughout the gastrointestinal tract. The notion that glial cells function solely as passive support cells has been refuted by compelling evidence that demonstrates that enteric glia are important homeostatic cells of the intestine. Active signalling mechanisms between enteric glia and neurons modulate gastrointestinal reflexes and, in certain circumstances, function to drive neuroinflammatory processes that lead to long-term dysfunction. Bidirectional communication between enteric glia and immune cells contributes to gastrointestinal immune homeostasis, and crosstalk between enteric glia and cancer stem cells regulates tumorigenesis. These neuromodulatory and immunomodulatory roles place enteric glia in a unique position to regulate diverse gastrointestinal disease processes. In this Review, we discuss current concepts regarding enteric glial development, heterogeneity and functional roles in gastrointestinal pathophysiology and pathophysiology, with a focus on interactions with neurons and immune cells. We also present a working model to differentiate glial states based on normal function and disease-induced dysfunctions.
Topics: Animals; Enteric Nervous System; Gastrointestinal Diseases; Gastrointestinal Motility; Homeostasis; Humans; Neuroglia; Signal Transduction
PubMed: 33731961
DOI: 10.1038/s41575-021-00423-7 -
Neurotherapeutics : the Journal of the... Jul 2020Interactions between central glial cells and neurons in the pain circuitry are critical contributors to the pathogenesis of chronic pain. In the central nervous system... (Review)
Review
Interactions between central glial cells and neurons in the pain circuitry are critical contributors to the pathogenesis of chronic pain. In the central nervous system (CNS), two major glial cell types predominate: astrocytes and microglia. Injuries or pathological conditions which evoke pain are concurrently associated with the presence of a reactive microglia or astrocyte state, which is characterized by a variety of changes in the morphological, molecular, and functional properties of these cells. In this review, we highlight the changes that reactive microglia and astrocytes undergo following painful injuries and insults and discuss the critical and interactive role these two cell types play in the initiation and maintenance of chronic pain. Additionally, we focus on several crucial mechanisms by which microglia and astrocytes contribute to chronic pain and provide commentary on the therapeutic promise of targeting these pathways. In particular, we discuss how the inflammasome in activated microglia drives maturation and release of key pro-inflammatory cytokines, which drive pain through neuronal- and glial regulations. Moreover, we highlight several potentially-druggable hemichannels and proteases produced by reactive microglia and astrocytes in pain states and discuss how these pathways regulate distinct phases during pain pathogenesis. We also review two emerging areas in chronic pain research: 1) sexually dimorphic glial cell signaling and 2) the role of oligodendrocytes. Finally, we highlight important considerations for potential pain therapeutics targeting glial cell mediators as well as questions that remain in our conceptual understanding of glial cell activation in pain states.
Topics: Analgesics; Animals; Astrocytes; Central Nervous System; Chronic Pain; Drug Delivery Systems; Ganglia, Spinal; Humans; Microglia; Neuroglia
PubMed: 32820378
DOI: 10.1007/s13311-020-00905-7 -
Neuron Jun 2020The habenula complex is appreciated as a critical regulator of motivated and pathological behavioral states via its output to midbrain nuclei. Despite this,...
The habenula complex is appreciated as a critical regulator of motivated and pathological behavioral states via its output to midbrain nuclei. Despite this, transcriptional definition of cell populations that comprise both the medial habenular (MHb) and lateral habenular (LHb) subregions in mammals remain undefined. To resolve this, we performed single-cell transcriptional profiling and highly multiplexed in situ hybridization experiments of the mouse habenula complex in naive mice and those exposed to an acute aversive stimulus. Transcriptionally distinct neuronal cell types identified within the MHb and LHb, were spatially defined, differentially engaged by aversive stimuli, and had distinct electrophysiological properties. Cell types identified in mice also displayed a high degree of transcriptional similarity to those previously described in zebrafish, highlighting the well-conserved nature of habenular cell types across the phylum. These data identify key molecular targets within habenular cell types and provide a critical resource for future studies.
Topics: Animals; Astrocytes; Endothelial Cells; Ependymoglial Cells; Gene Expression Profiling; Gene Ontology; Habenula; Mice; Microglia; Neuroglia; Neurons; Oligodendroglia; RNA-Seq; Single-Cell Analysis; Zebrafish
PubMed: 32272058
DOI: 10.1016/j.neuron.2020.03.011 -
Advances in Experimental Medicine and... 2019Neuroglia represent a diverse population of non-neuronal cells in the nervous systems, be that peripheral, central, enteric or autonomic nervous system. Arguably, these... (Review)
Review
Neuroglia represent a diverse population of non-neuronal cells in the nervous systems, be that peripheral, central, enteric or autonomic nervous system. Arguably, these cells represent about half of the volume of the human brain. This volumetric ratio, and by extension glia to neurone ratio, not only widely differ depending on the size of the animal species brain and its positioning on the phylogenetic tree, but also vary between the regions of an individual brain. Neuroglia derived from a dual origin (ectoderm and mesodermal) and in an assorted morphology, yet their functional traits can be mainly classified into being keepers of homeostasis (water, ions, neurotransmitters, metabolites, fuels, etc.) and defenders (e.g., against microbial organisms, etc.) of the nervous system. As these capabilities go awry, neuroglia ultimately define their fundamental role in most, if not, all neuropathologies. This concept presented in this chapter serves as a general introduction into the world of neuroglia and subsequent topics covered by this book.
Topics: Animals; Homeostasis; Humans; Neuroglia; Neurons; Neurotransmitter Agents; Phylogeny
PubMed: 31583582
DOI: 10.1007/978-981-13-9913-8_1