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Neuronal and glial structural plasticity induced by drugs of abuse

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195985 Year: Pages: 90 DOI: 10.3389/978-2-88919-598-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-03-10 08:14:32
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Drugs of abuse induce a host of alterations in brain structure and function, ranging from changes in gene expression and epigenetic processes to aberrant synaptic plasticity to volumetric changes in discrete brain regions. These alterations can be drug class-specific, and are not confined to neurons, as drugs of abuse also induce molecular and cellular alterations in various glial cell types such as astrocytes and microglia. The phenomenon of drug-induced plasticity includes changes in dendritic branching and architecture, dendritic spine density and morphology, astrocyte-neuronal interactions, dysregulation of glutamatergic and GABAergic signaling, and alterations in myelination or microglial phenotype. This drug-induced "rewiring" of the brain at numerous levels can contribute to the development, maintenance, and persistence of the addicted state, as well as associated deficits in normal cognitive functioning. The aim of this Research Topic is to collect recent and important findings related to the structural alterations produced by drug of abuse in neurons, glial, and other cell types of the central nervous system.

Keywords

plasticity --- Dendrite --- Spine --- Glutamate --- Dopamine --- GABA --- Neuron --- glia --- astrocyte --- Addiction

Ionotropic Glutamate Receptors Trafficking in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450893 Year: Pages: 141 DOI: 10.3389/978-2-88945-089-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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The knowledge about the properties and importance of ionotropic glutamate receptor trafficking is ever increasing. Importantly, the pace of the progress has been accelerated in recent years. Here, our contributors provide a) reviews on specific topics that present an up-to-date overview of the field, as well as b) original articles with the relevant new findings.

Ubiquitin and the Brain: Roles of Proteolysis in the Normal and Abnormal Nervous System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452859 Year: Pages: 241 DOI: 10.3389/978-2-88945-285-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Proteolysis by the ubiquitin-proteasome pathway (UPP) in the nervous system has been extensively studied both in the context of normal physiological function as well as abnormal pathological conditions. Although ubiquitin was used as a marker of brain pathology, the normal functions of the UPP were not studied much in the nervous system until the 1990s. The early investigations focused on synaptic plasticity which was followed by studies on the roles of protein degradation in the development of the nervous system. Research on the role of abnormal roles of the UPP follows a parallel trajectory. Since the 2000s, the field has grown to encompass many subareas of research and several model systems. Despite the progress made, many unanswered questions still remain. For example, there are many unknowns about the precise spatial and temporal control of protein degradation in the normal nervous system. With respect to the roles of proteolysis in brain pathology a major challenge is to elucidate the connection between impaired protein degradation and disease progression. In addition, in-depth studies of the roles of ubiquitin-proteasome-mediated proteolysis in neurodegenerative diseases are promising in identifying therapeutic targets. This ebook contains original research papers and insightful reviews that cover several aspects of proteolysis by the UPP and its physiological as well as pathological functions in the nervous system.

MR Spectroscopy in Neuropsychiatry

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455249 Year: Pages: 90 DOI: 10.3389/978-2-88945-524-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Psychiatry
Added to DOAB on : 2019-01-23 14:53:42
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Neuropsychiatric disorders, covering both psychotic and depressive disorders, but also autism and attention-deficit hyperactivity disorder (ADHD), are characterized by abnormal behavior and brain structure. Accumulating evidence suggests that altered neurochemistry plays a role in these disorders and may have a causal relationship with the observed behavioral and structural abnormalities. To improve the understanding of neurochemical anomalies and (patho)physiological changes in psychiatric conditions, in vivo assessment of the affected tissue, the brain, is wanted and needed. Magnetic resonance spectroscopy (MRS) is a non-invasive technique which allows in vivo assessment of the molecular composition of brain tissues and identification of metabolites involved in physiological and pathological processes, which is otherwise virtually impossible. Only in the last decade with the development of high field MR methodologies, MRS has become sensitive enough for broader use in clinical studies. The implications are many, but proper guidance and elucidation of the pros and cons for the specific methods is needed to optimally exploit the potential.This Research Topic updates the reader on the possibilities and pitfalls of MRS today and highlights methodologies and applications for the future.

Transcellular Cycles Underlying Neurotransmission

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196548 Year: Pages: 105 DOI: 10.3389/978-2-88919-654-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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Synaptic transmission demands the operation of a highly specialized metabolic machinery involving the transfer of metabolites and neurotransmitters between neurons, astrocytes and microvessels. In the last years, important advances have occurred in our understanding of the mechanisms underlying cerebral activation, neuroglial coupling and the associated neurovascular response. Briefly, exacerbated oxygen consumption in stimulated neurons is thought to trigger glycolytic lactate and glucose transfer from astrocytes which, in turn, obtain these fuels from the microvasculature. Neurotransmitter release is made possible by a combination of transcellular cycles exchanging metabolites between these three compartments, returning eventually the synapsis to its pre-firing situation in the resting periods. In spite of the enormous progresses achieved in recent years, the drivers determining the predominant direction of the fluxes, their quantitative contribution and their energy requirements, have remained until today incompletely understood, more particularly under the circumstances prevailing in vivo. In many instances, progress derived from the implementation of novel methodological approaches including advanced neuroimaging and neurospectroscopy methods. As a consequence, literature in the field became vast, diverse and spread within journals of different specialities. The e-book "Transcellular cycles underlying neurotransmission" aims to summaryze in a single volume, recent progress achieved in hypothesis, methods and interpretations on the trafficking of metabolites between neurons and glial cells, and the associated mechanisms of neurovascular coupling.

Astrocytic-neuronal-astrocytic Pathway Selection for Formation and Degradation of Glutamate/GABA

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192434 Year: Pages: 168 DOI: 10.3389/978-2-88919-243-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology --- Medicine (General) --- Internal medicine
Added to DOAB on : 2015-11-16 15:44:59
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Endocrinological research early recognized the importance of intercellular interactions and realized the importance of glutamatergic and GABAergic signaling. In turn this signalling depends on elaborate interactions between astrocytes and neurons, without which neurons would be unable to produce, reuse and metabolize transmitter glutamate and GABA. Details of these subjects are described in this Research Topic by key investigators in this field. It focuses on the intricate and extremely swift pathway producing these amino acid transmitters from glucose in brain but also discusses difficulties in determining expression of some of the necessary genes in astrocytes and related processes in pancreatic islets. However, it does not discuss how closely associated astrocytes and neurons are anatomically, enabling these interactions. This is elegantly shown in this cover image, kindly provided by Professor Andreas Reichenbach (University of Leipzig, Germany).

Imaging Synapse Structure and Function

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451753 Year: Pages: 125 DOI: 10.3389/978-2-88945-175-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
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Development of new imaging technologies in recent years has transformed neuroscience in profound ways. Following on the heels of the revolution based on the Green Fluorescent Protein, refined genetically-encoded fluorescent reporters and genetic targeting strategies now enable optical recording of synaptic transmission in defined neuronal populations at speeds approaching the enviable temporal resolution of electrophysiology. Super-resolution light microscopy permits observation of synapses and their molecular machinery at sub-diffraction resolution. At the ultrastructural level, automated forms of electron microscopy, improvements in specimen fixation methods, and recent efforts to correlate data from light and electron micrographs now make the reconstruction of functional neural circuits a reality. Finally, the use of optogenetic actuators, such as channelrhodopsins, allows precise temporal and spatial manipulation of neuronal activity and is revealing profound insights into the organization of neural circuits and their roles in behavior. This research topic highlights recent advances in both light and electron microscopy, with a specific focus on approaches that combine innovations from several different fields to obtain novel information about synapse structure and function. We are confident that this collection of articles - three original research papers, six reviews, one methods paper and one perspective article - will enable neuroscientists to achieve the next generation of experiments aimed at cracking the neural code.

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.

Targets, Tracers and Translation – Novel Radiopharmaceuticals Boost Nuclear Medicine

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ISBN: 9783039213139 / 9783039213146 Year: Pages: 214 DOI: 10.3390/books978-3-03921-314-6 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-12-09 11:49:15
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This is the fourth Special Issue in Pharmaceuticals within the last six years dealing with aspects of radiopharmaceutical sciences. It demonstrates the significant interest and increasing relevance to ameliorate nuclear medicine imaging with PET or SPECT, and also radiotherapeutical procedures.Numerous targets and mechanisms have been identified and have been under investigation over the previous years, covering many fields of medical and clinical research. This development is well illustrated by the articles in the present issue, including 13 original research papers and one review, covering a broad range of actual research topics in the field of radiopharmaceutical sciences.

Keywords

breast cancer --- 68Ga --- GRPR --- NPY(Y1)R --- peptide heterodimers --- PET/CT imaging --- sentinel lymph node --- dextran --- mannose --- 99mTc-radiopharmaceuticals --- glutamate --- metabotropic glutamate receptor subtype 5 --- [18F]PSS232 --- ketamine --- ceftriaxone --- positron emission tomography --- allosteric modulator --- MMPEP --- ABP688 --- pretargeting --- Fusarinine C --- rituximab --- click chemistry --- multimerization --- PET --- gallium-68 --- carbonic anhydrase IX --- girentuximab --- renal cell carcinomas --- 177Lu-radiopharmaceuticals --- radioimmunotherapy --- neuroinflammation --- microglia --- carbon-11 --- radiochemistry --- positron emission tomography --- hypoxia --- radiosensitizer --- benzotriazine-1,4-dioxide (BTDO), benzotriazine-1-monoxide (BTMO), tirapazamine (TPZ), SR 4317 --- radioiodination --- tropomyosin receptor kinase --- positron emission tomography --- neurodegeneration --- oncogenic fusions --- [11C]meta-hydroxyephedrine --- radiosynthesis --- separation --- apparent molar activity --- cholecystokinin-2 receptor --- minigastrin --- molecular imaging --- radiometals --- technetium-99m --- hydrazinonicotinic acid (HYNIC) --- PSMA-617 --- salivary gland uptake --- prostate cancer --- endoradiotherapy --- Chloramine T --- electrophilic radioiodination --- iodine-131 --- Iodo-Gen® --- oxidizing agent --- ?-CIT. --- tumor hypoxia --- PET --- small animal imaging --- azomycin nucleosides --- [18F]FMISO --- bombesin --- gastrin-releasing peptide --- gastrin-releasing peptide receptor --- tumor targeting --- 99mTc-radioligand --- metabolic stability --- neprilysin-inhibition --- phosphoramidon --- n/a --- n/a

Cancer Metabolomics 2018

Authors: --- ---
ISBN: 9783039213450 / 9783039213467 Year: Pages: 184 DOI: 10.3390/books978-3-03921-346-7 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2019-12-09 11:49:15
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The metabolomics approach, defined as the study of all endogenously-produced low-molecular-weight compounds, appeared as a promising strategy to define new cancer biomarkers. Information obtained from metabolomic data can help to highlight disrupted cellular pathways and, consequently, contribute to the development of new-targeted therapies and the optimization of therapeutics. Therefore, metabolomic research may be more clinically translatable than other omics approaches, since metabolites are closely related to the phenotype and the metabolome is sensitive to many factors. Metabolomics seems promising to identify key metabolic pathways characterizing features of pathological and physiological states. Thus, knowing that tumor metabolism markedly differs from the metabolism of normal cells, the use of metabolomics is ideally suited for biomarker research. Some works have already focused on the application of metabolomic approaches to different cancers, namely lung, breast and liver, using urine, exhaled breath and blood. In this Special Issue we contribute to a more complete understanding of cancer disease using metabolomics approaches.

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