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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

The Role of Glia in Plasticity and Behavior

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196906 Year: Pages: 104 DOI: 10.3389/978-2-88919-690-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Glial cells are no longer considered passive bystanders in neuronal brain circuits. Not only are they required for housekeeping and brain metabolism, they are active participants in regulating the physiological function and plasticity of brain circuits and the online control of behavior both in invertebrate and vertebrate model systems. In invertebrates, glial cells are essential for normal function of sensory organs (C. elegans) and necessary for the circadian regulation of locomotor activity (D. melanogaster). In the mamallian brain, astrocytes are implicated in the regulation of cortical brain rhythms and sleep homeostasis. Disruption of AMPA receptor function in a subset of glial cell types in mice shows behavioral deficits. Furthermore, genetic disruption of glial cell function can directly control behavioral output. Regulation of ionic gradients by glia can underlie bistability of neurons and can modulate the fidelity of synaptic transmission. Grafting of human glial progenitor cells in mouse forebrain results in human glial chimeric mice with enhanced plasticity and improved behavioral performance, suggesting that astrocytes have evolved to cope with information processing in more complex brains. Taken together, current evidence is strongly suggestive that glial cells are essential contributors to information processing in the brain. This Research Topic compiles recent research that shows how the molecular mechanisms underlying glial cell function can be dissected, reviews their impact on plasticity and behavior across species and presents novel approaches to further probe their function.

Keywords

glia --- Astrocytes --- plasticity --- Behavior --- Gq --- DREADD --- C. elegans --- Hippocampus --- Cerebellum --- Cortex

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.

Imaging and monitoring astrocytes in health and disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193936 Year: Pages: 189 DOI: 10.3389/978-2-88919-393-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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Astrocytes are key cellular partners to neurons in the brain. They play an important role in multiple processes such as neurotransmitter recycling, trophic support, antioxidant defense, ionic homeostasis, inflammatory modulation, neurovascular and neurometabolic coupling, neurogenesis, synapse formation and synaptic plasticity. In addition to their crucial involvement in normal brain physiology, it is well known that astrocytes adopt a reactive phenotype under most acute and chronic pathological conditions such as ischemia, trauma, brain cancer, epilepsy, demyelinating and neurodegenerative diseases. However, the functional impact of astrocyte reactivity is still unclear. During the last decades, the development of innovative approaches to study astrocytes has significantly improved our understanding of their prominent role in brain function and their contribution to disease states. In particular, new genetic tools, molecular probes, and imaging techniques that achieve high spatial and temporal resolution have revealed new insight into astrocyte functions in situ. This Research Topic provides a collection of cutting-edge techniques, approaches and models to study astrocytes in health and disease. It also suggests new directions to achieve discoveries on these fascinating cells.

Progenitor diversity and neural cell specification in the central nervous system

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196838 Year: Pages: 107 DOI: 10.3389/978-2-88919-683-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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The central nervous system continuously perceives, integrates, processes and generates information. These complex functions rely on the detailed elaboration of its cellular network and on the myriads of individual, highly differentiated and specialized cell types, classically subdivided into neurons, astrocytes and oligodendrocytes. The specification of these individual populations begins early during development with less differentiated, yet already partly restricted, progenitor cells. Anatomically located in dedicated germinative niches, neural progenitors perceive the influence of diffusible molecules of various natures and concentrations. These signals result in the initial specialization of cohorts of progenitors that express unique combinations of transcription factors. It is now clearly established that both extrinsic and intrinsic signals act in concert to determine the fate potentials of these progenitor cohorts. This limitation increases over time, adult neural progenitors being more restricted than their developmental counterparts. Nevertheless, recent data have shown that the fate restriction of neural progenitors, as well as that of their progenies, can be overwritten upon selected intrinsic factor expression, not only during development but also in adulthood. This e-book is a collection of original research studies along with review articles that, together, provide insights into the vast spatiotemporal diversity of neural progenitors, and the various factors that govern their fate potential.

All 3 Types of Glial Cells Are Important for Memory Formation

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450251 Year: Pages: 150 DOI: 10.3389/978-2-88945-025-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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The vertebrate brain contains neurons and 3 classical types of glia cells, astrocytes, oligodendrocytes and microglia. Astrocytes and microglia have mainly been studied in gray matter, whereas oligodendrocytes myelinate white matter tracts. Until recently microglial effects were considered mainly during pathological conditions, but is now known that microglia plays important roles also in normal brain function. All these 3 glial cell types and their collaboration with neurons are important for learning. The concept that glia cells are important for cognitive function is not new. A glial-neuronal theory of brain function was proposed by Galambos in 1961. Hyden and Egyhazi demonstrated glial RNA changes in microdissected glia cells during learning in rats in 1963, and astrocytic and oligodendrocytic involvement of K+-mediated effects of learning has been suggested and/or demonstrated from the 1960’s and onwards as recently reviewed by Hertz and Chen (Neuroscience and Biobehavioural Reviews, 2016). In 1969 van den Berg et al. showed compartmentation of glutamate in brain and thus of production of the neurotransmitters glutamate and GABA, which are essential for learning. That glutamate is synthesized in astrocytes because they in contrast to neurons express the enzyme pyruvate carboxylase was demonstrated 10-15 years later by Yu et al. in cultured astrocytes and Shank et al. in intact brain tissue. However, the present e-book focuses on more recent developments. Most information is available about astrocytic roles in learning. The importance of astrocytes in the tripartite synapse and of microglia in the tetrapartite synapse is illustrated in the front-page figure, which emphasizes the role of gliotransmitters and of Ca2+ transport through gap junctions, coupling astrocytes into a functional syncytium. Astrocytes are important for establishments of brain rhythms, which may differ in different cognitive tasks, and although the exact reason why knock-out of the astrocytic water channel AQP4 impairs memory remains to be established, several possibilities are discussed. The importance of the two astrocyte specific processes glutamate and glutamine formation and glycogenolysis is discussed in considerable detail. Glycogenolysis is important not only for astrocytic processes involved in learning, but also for those in neurons because glycolytically derived lactate has signaling functions in the extracellular space and may be accumulated in minute quantities into very specific and small neuronal structures. Some neurotransmitters stimulating glycogenolysis are also involved in psychiatric disease. Noradrenaline, released from locus coeruleus exerts direct effects on both astrocytes and neurons and in addition promotes secretion of corticotropin-releasing hormone and adrenocorticotrophic hormone (ACTH) in brain, and of glucocorticoids from the adrenal cortex, all of which are responsible for stress effects on learning. Lead causes memory impairment by inhibition of glutamine formation due to oxidative stress and reduced effectiveness of the glutathione system. The many adverse effects of fetal alcohol exposure on behaviour and learning are caused by a multitude of effects on all three types of glia cells. Traumatic brain injury also exerts multifactorial effects, including microglia/astrocyte-induced secretion of neuroinflammatory molecules and axonal disruption and oligodendrocytic dysfunction. In normal brain oligodendrocytes respond to the depolarization caused by neuronal activity with accelerated conduction velocity and increased compound action potentials which facilitate learning.

Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function

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ISBN: 9783039216888 / 9783039216895 Year: Pages: 240 DOI: 10.3390/books978-3-03921-689-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
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Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these enzymes potential biological markers and therapeutic targets. This Special Issue covers recent advances in the molecular mechanisms and biological functions of MKPs and small-size atypical DUSPs, and their relevance in human disease.

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