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Glial Cells: Managers of Neuro-immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198351 Year: Pages: 224 DOI: 10.3389/978-2-88919-835-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Immune responses within the brain are still scarcely explored. Nerve tissue damage is accompanied by the activation of glial cells, primarily microglia and astroglia, and such activation is responsible for the release of cytokines and chemokines that maintain the local inflammatory response and actively recruit lymphocytes and monocytes to the damaged areas. Theoretically, these responses are designed to repair the brain damage. However, alterations, or a chronic perpetuation of these responses may underlie a number of neuro-pathologies. It is thought that each inflammatory scenario within the brain have a specific biochemical footprint characterized by the release of determined cytokines, chemokines and growing factors able to define particular immunological responses. Alongside, glial cells transform their cell body, become larger and develop higher number of branches adopting an active morphological phenotype. These changes are related with the search of interactions with other cells, such as bystander resident cells of the brain parenchyma, but also cells homing from the blood stream. In this process, microglia and astrocytes communicates with other cells by the formation of specific intercellular connections that are still poorly understood. These interactions are complex and entail the arrangement of cytoskeletal compounds, secretory and phagocytic domains. In this particular crosstalk there is a two-way communication in which glial cells and target cells come together establishing interfaces with specific information exchange. This way, glial cells orchestrate the particular response recruiting cellular subsets within the central nervous system and organizing the resolution of the brain damage. In this Frontiers Research Topic, we compile a selection of articles unfolding diverse aspects of glial-derived inflammation, focused on neurodegenerative diseases and other nervous system disorders, with special emphasis on microglia/macrophages as leading actors managing neuro-immunity.

Glial Plasticity in Depression

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199990 Year: Pages: 99 DOI: 10.3389/978-2-88919-999-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-01-19 14:05:46
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Major depression is a highly prevalent disorder that poses a significant social burden in society nowadays. The pathophysiology of this disease is still poorly understood but growing evidence suggests that impaired neuron and glial plasticity may be a key underlying mechanism for the precipitation of the disorder. One of the most surprising findings in this field was the involvement of glial cells in the pathophysiology of major depression and in the action of antidepressants, namely in mechanisms related with adult neurogenesis imbalances or dendritic arborization impairments. In particular, several works refer to alterations in the morphology and numbers of astrocytes, microglia and oligodendrocytes in the context of depression in human patients or animal models of depression. These observations were linked to functional evidences and suggested to underlie the pathophysiology of depression. Among others, these include impairments in the cross-talk between glia and neurons, changes in the level of neurotransmitter or immunoactive substances, myelination status, synapse formation, maintenance, or elimination. In addition to the implication of glia in the pathophysiology of depression, a number of studies is ascribing glia pathways to classically accepted antidepressant mechanisms. Therefore, it is noteworthy to elucidate the role of glia in the effect provided by antidepressant treatment in order to better understand secondary effects and elucidate alternative targets for treatment.

Microglia in Health and Disease: A Unique Immune Cell Population

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456017 Year: Pages: 108 DOI: 10.3389/978-2-88945-601-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:43
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Microglia are essential for the development and function of the adult brain. Their ontogeny, together with the absence of turnover from the periphery and the singular environment of the central nervous system (CNS), make microglia a unique cell population compared to other tissue-macrophages. The unique properties and functions of microglial cells, such as their role in synaptic pruning or the exceptional capacity to scan the brain parenchyma and rapidly react to its perturbations, have emerged in recent years. In the coming years, understanding how microglia acquire and maintain their unique profiles in order to fulfil distinct tasks in the healthy CNS and how these are altered in disease, will be essential to develop strategies to diagnose or treat CNS disorders with an immunological component.This Research Topic covers several aspects of microglial biology, ranging from their origin and the functional role of microglia during development and lifespan, their molecular properties compared with other brain and peripheral immune cells to microglial phenotypes and functional states in neurodegenerative diseases and brain tumours. In conclusion, the present Research Topic provides a comprehensive overview of our current understanding of several cellular and molecular mechanisms that make microglia a unique immune cell population within the healthy CNS as well as under inflammatory, neurodegenerative and tumorigenic processes.

Microglial Polarization in the Pathogenesis and Therapeutics of Neurodegenerative Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455256 Year: Pages: 327 DOI: 10.3389/978-2-88945-525-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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Microglia-mediated neuroinflammation is one of the shared prominent hallmarks among various forms of neurodegeneration. Depending on the milieu in which microglia become activated, the polarization of microglia shows to be heterogeneous with diverse functional phenotypes that range from pro-inflammatory phenotypes to immunosuppressive phenotypes. Therefore, targeting microglial polarization holds great promise for the treatment of neurodegeneration.This eBook focuses on the potential mechanisms of microglial polarization that are critically associated with a broad spectrum of neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), Traumatic brain injury (TBI), glaucomatous neurodegeneration and prion diseases. This topic also involves the therapeutic targeting of microglial polarization by nutritional and pharmacological modulators. Moreover, this topic describes advanced technologies employed for studying microglia. Age-related changes in microglia functions are also discussed.Overall, this eBook provides comprehensive understandings of microglial polarization in the course of neurodegeneration, linking with aging-related microglial alterations and technologies developed for microglial studies. Hopefully, it will also give comprehensive insights into various aspects of therapeutic treatment for neurodegeneration, through targeting microglial polarization.

Dual role of microglia in health and disease: pushing the balance towards repair

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194926 Year: Pages: 101 DOI: 10.3389/978-2-88919-492-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-11-16 15:44:59
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Microglial cells play a vital role in the innate immune response occurring in the Central Nervous System (CNS). Under physiologic conditions, microglia dynamically patrol the brain parenchyma and participate in the remodeling of active neuronal circuits. Accordingly, microglia can boost synaptic plasticity by removing apoptotic cells and by phagocytizing axon terminals and dendritic spines that form inappropriate neural connections. Upon brain and spinal cord injury or infection, microglia act as the first line of immune defense by promoting the clearance of damaged cells or infectious agents and by releasing neurotrophins and/ or proneurogenic factors that support neuronal survival and regeneration.Recently, two main pathways were suggested for microglia activation upon stimuli. Classical activation is induced by Toll-like receptor agonists and Th1 cytokines and polarizes cells to an M1 state, mainly leading to the release of TNF-alpha, IL-6 and nitric oxide and to grave neural damage. Alternative activation is mediated by Th2 cytokines and polarizes cells to an M2a state inducing the release of antiinflammatory factors. These findings have further fueled the discussion on whether microglia has a detrimental or beneficial action (M1 or M2-associated phenotypes, respectively) in the diseased or injured CNS and, more importantly, on whether we can shift the balance to a positive outcome.Although microglia and macrophages share several common features, upon M1 and M2 polarizing conditions, they are believed to develop distinct phenotypic and functional properties which translate into different patterns of activity. Moreover, microglia/macrophages seem to have developed a tightly organized system of maintenance of CNS homeostasis, since cells found in different structures have different morphology and specific function (e.g. meningeal macrophages, perivascular macrophages, choroid plexus macrophages). Nevertheless, though substantial work has been devoted to microglia function, consensus around their exact origin, their role during development, as well as the exact nature of their interaction with other cells of the CNS has not been met.This issue discusses how microglial cells sustain neuronal activity and plasticity in the healthy CNS as well as the cellular and molecular mechanisms developed by microglia in response to injury and disease. Understanding the mechanisms involved in microglia actions will enforce the development of new strategies to promote an efficient CNS repair by committing microglia towards neuronal survival and regeneration.

Never-resting microglia: physiological roles in the healthy brain and pathological implications

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193691 Year: Pages: 172 DOI: 10.3389/978-2-88919-369-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic reviewed the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic discussed the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the regulation of adult neurogenesis as well as hippocampal learning and memory; among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic also summarized the current view of microglial nomenclature, phenotypes, origin and differentiation, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state have been discussed. In conclusion, this Research Topic sought to emphasize how the current research in neuroscience is challenged by never-resting microglia.

Single Membrane Channels Formed by Connexins or Pannexins: Focus on the Nervous System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198900 Year: Pages: 241 DOI: 10.3389/978-2-88919-890-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-01-19 14:05:46
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Given that the extremely elaborated and dynamic functions performed by the nervous system require the close synchronization of brain cells, complex organisms have developed different mechanisms of intercellular communication. At this regard, paracrine signaling between neighboring cells is currently recognized as one of the most widely distributed mechanisms of synchronization in the brain parenchyma. In mammals, paracrine signaling is in part mediated by single membrane channels formed by connexins (connexons/hemichannels) or pannexins (pannexons), which are two different membrane protein families composed of about 20 and 3 members, respectively. Single membrane channels formed by these proteins serve as aqueous pores permeable to ions and small molecules, allowing the diffusional exchange between the intra- and extracellular milieu. Thus, connexin hemichannels and pannexons permit the release of significant quantities of autocrine/paracrine signaling molecules (e.g., ATP, glutamate, NAD+, adenosine and PGE2) into the extracellular milieu, as well as the uptake of small molecules. An increasing body of evidence has revealed that connexin hemichannels and pannexons play a crucial role in a plethora of brain processes including blood flow regulation, Ca2+ wave propagation, memory consolidation, glucose sensing and cell migration and adhesion. Considering the multiple cell signaling functions of these channels, their dysregulation is proposed not only as potential pathological biomarker, but it has been implicated in the pathogenesis and progression of diverse brain diseases (e.g., meningitis, Alzheimer’s disease and stroke). The aim of this Research Topic is to gather a collection of original research articles, method, protocols, short communications, opinions, perspectives, as well as review articles, providing the latest progress and insights in the field of connexin hemichannels and pannexons in the nervous system. Within this volume we plan to cover from basic research including channel structure, regulation, pharmacology and trafficking; to different biological functions in the physiology (behavior, plasticity, neurogenesis, blood flow control, neuron-glia crosstalk, cell migration and differentiation) as well as in the pathophysiology (neuroinflammation, mutation-related diseases, glial dysfunction and neurodegeneration) of the nervous system. We hope that this collection of articles will serve to understand how the signaling of connexin hemichannels and pannexons influences both normal and pathological brain function.

Keywords

astrocyte --- Microglia --- Neuron --- Brain --- glia --- connexin --- pannexin --- hemichannel --- connexon --- pannexon

Cytokines as Players of Neuronal Plasticity and Sensitivity to Environment in Healthy and Pathological Brain

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197682 Year: Pages: 158 DOI: 10.3389/978-2-88919-768-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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It is now accepted that immune molecules are not only present within the brain during pathology but they exert physiological functions in the "healthy" brain as well. Increasing evidence points to a neuro-modulatory role of cytokines and chemokines (CHEMOtactic cytoKINES) in basal transmission and plasticity processes where signaling between peri-synaptic astrocytes, microglia and neurons plays an important role. Nevertheless, the exact mechanisms as to how cytokines, and in particular chemokines, participate in the molecular and cellular processes thought to subserve memory formation, plasticity processes and responsiveness to environmental stimuli remain to be clarified. Interestingly, in in vitro preparations, molecules like TNF-a, interleukin (IL)-1ß, IL-6, CX3CL1, CXCL12, CCL2 and CCL3 are implicated in synaptic formation and scaling, in modulation of glutamatergic transmission, in plasticity and neurogenesis, in particular in the hippocampus. The hippocampus is an extremely plastic structure, one of the main neurogenic niches in the adult brain, that exhibits a marked sensibility to environmental stimuli. Indeed exposure of mice to environmental enrichment (EE) modifies learning and memory abilities increasing neurogenesis and neuronal plasticity whether exposure to severe stressful experiences diminishes neurotrophic support, impairs neurogenesis, plasticity and cognition. In the hippocampus cytokines play a key role in mediating both positive as well as negative effects of the environment affecting neuronal plasticity also in stress related pathologies, such as depression. It has been reported that mice lacking type 1 receptor for IL-1 display impaired hippocampal memory and LTP that are restored by EE; moreover negative effects on neuronal plasticity (and thus behavior) induced by stress exposure can be prevented by blocking IL-1 activity. In addition, mice lacking IL-6 have improved cognitive functions whereas the absence of microglia-driven CX3CR1 signaling increases hippocampal plasticity and spatial memory occluding the potentiating effects of EE. However, the factors mediating the effect of environmental stimuli on behavior and plasticity has been only partially identified. Interestingly, it has been suggested that chemokines can play a key role in the flexibility of hippocampal structure and may modulate neuronal signaling during behavior. The question is how cytokines may translate environmental stimuli in plasticity and behavioral changes. This research topic is proposed to explore the role of cytokines, and more in particular chemokines, in the modulation of neuronal activity as a fundamental step for the correct brain wiring, function and susceptibility to environment. We encourage the submission of original research reports, review articles, commentaries, perspectives or short communications, in the following (but not limited to) topics:- Role of cytokines and chemokines in neuronal plasticity- Immune molecules and responsiveness to environment- Role of chemokine in the flexibility of hippocampal structure

Neuroinflammation and Behaviour

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196029 Year: Pages: 181 DOI: 10.3389/978-2-88919-602-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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The brain and immune system are involved in an intricate network of bidirectional communication. This relationship is vital for optimal physiological and psychological development and functioning but can also result in unwanted outcomes. In particular, this interaction plays an important role in cognition, mood and behaviour. Neuroinflammation is known to contribute to neurological and affective disorders including impaired learning and memory, depressive, anxiety and schizoaffective symptoms, as well as pain. The development of these conditions often occurs on the backdrop of pre-existing physical illnesses which give rise to increased activation of the immune system, such as cancer, obesity, infection and autoimmune disorders. Similarly, psychological states can alter regulation of the immune system. This has been most extensively studied in the context of stress and immune function. Understanding the underlying mechanisms that lead to the onset of inflammation-induced neuropathology and stress-induced immune suppression will contribute to the development of novel and effective treatment strategies for both the disease and its neurological side effects. In this research topic we explored the relationship between the immune system and the brain throughout life. We include both original research and review papers from animal, clinical and molecular perspectives.

Minding Glial Cells in the Novel Understandings of Mental Illness

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451579 Year: Pages: 275 DOI: 10.3389/978-2-88945-157-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
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Traditionally, abnormalities of neurons and neuronal networks including synaptic abnormalities and disturbance of neurotransmitters have dominantly been believed to be the main causes of psychiatric disorders. Recent cellular neuroscience has revealed various unknown roles of glial cells such as astrocytes, oligodendrocytes and microglia. These glial cells have proved to continuously contact with neurons /synapses, and have been shown to play important roles in brain development, homeostasis and various brain functions. Beyond the classic neuronal doctrine, accumulating evidence has suggested that abnormalities and disturbances of neuron-glia crosstalk may induce psychiatric disorders, while these mechanisms have not been well understood. This Research Topic of the Frontiers in Cellular Neuroscience will focus on the most recent developments and ideas in the study of glial cells (astrocytes, oligodendrocytes and microglia) focusing on psychiatric disorders such as schizophrenia, mood disorders and autism. Not only molecular, cellular and pharmacological approaches using in vitro / in vivo experimental methods but also translational research approaches are welcome. Novel translational research approaches, for example, using novel techniques such as induced pluripotent stem (iPS) cells, may lead to novel solutions. We believe that investigations to clarify the correlation between glial cells and psychiatric disorders contribute to a novel understanding of the pathophysiology of these disorders and the development of effective treatment strategies.

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