Brain Mitochondria Distribution And Function

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Brain Mitochondria

Author : Silvia Lores-Arnaiz
Publisher :
ISBN 13 : 9781536166507
Total Pages : 0 pages
Book Rating : 4.1/5 (665 download)

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Book Synopsis Brain Mitochondria by : Silvia Lores-Arnaiz

Download or read book Brain Mitochondria written by Silvia Lores-Arnaiz and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Brain mitochondria: Distribution and Function" offers an overview of significant findings regarding physiological, toxicological and pathological aspects of brain mitochondria properties and their relevant role in cellular bioenergetics. Essential physiological processes such as cell respiration and ATP synthesis, the maintenance of calcium homeostasis, reactive oxygen species generation and apoptotic cell signaling performed by mitochondria are described in the different chapters of this volume. In particular, the importance of specific calcium signaling at synaptic level and its relationship with mitochondrial bioenergetics are extensively described. Being that high energy demands are required at synaptic level for neurotransmission, mitochondrial distribution becomes relevant for essential neuronal processes. Differential bioenergetic characteristics of neuronal, astrocytic and glial mitochondria are discussed. Interestingly, new insights on the interaction between neurotensinergic and nitrergic systems are detailed, based on experimental evidences of the effect of neurotensin receptors blockade on nitric oxide production and mitochondrial function. The chapters describing metal neurotoxicity provide a comprehensive view of the effects of different metals on brain mitochondrial function and their consequences for human health. The impact of iron and copper overload on brain oxidative redox balance and mitochondrial function is fully detailed, focusing on the role of metal-induced neuronal damage on the incidence and progression of neurodegenerative diseases. In addition, a complete revision of the mechanisms underlying heavy metal-mediated damage to brain mitochondria is presented. Neurotoxic effects of arsenic, thallium, lead, cadmium and mercury have been associated with cell bioenergetics impairment, exacerbated production of oxygen free radicals, and induction of intrinsic pathway of apoptosis. Mitochondrial function can also be impaired by treatment with different drugs acting at CNS level. The understanding of the effects of pharmacological agents, abuse drugs, herbicides and insecticides at mitochondrial level can contribute to elucidate the molecular mechanisms involved in neurodegeneration. In this context, the neuroprotective effect of different compounds targeting mitochondrial integrity and function is discussed. Furthermore, mitochondrial alterations, oxygen radicals generation and nitric oxide production are characterized in relation to CNS pathology and hypoxia conditions. Mitochondrial complex I inactivation, oxidative stress and impairment of mitochondrial nitric oxide synthesis are characteristic features of the mitochondrial dysfunction observed in Parkinson's disease and other CNS pathologies. In addition, exposure to hypoxic conditions can affect nitric oxide generation and mitochondrial physiology, with different responses depending on the brain area. As a whole, the understanding of the alterations in mitochondrial distribution and function in the brain associated with neurotoxicity and neurodegeneration may contribute to the knowledge of the role of mitochondria in maintaining the balance between health and disease.

Mitochondrial Dysfunction

Author : Lawrence H. Lash
Publisher : Elsevier
ISBN 13 : 1483218619
Total Pages : 527 pages
Book Rating : 4.4/5 (832 download)

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Book Synopsis Mitochondrial Dysfunction by : Lawrence H. Lash

Download or read book Mitochondrial Dysfunction written by Lawrence H. Lash and published by Elsevier. This book was released on 2013-10-22 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.

Discovering the Brain

Author : National Academy of Sciences
Publisher : National Academies Press
ISBN 13 : 0309045290
Total Pages : 195 pages
Book Rating : 4.3/5 (9 download)

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Book Synopsis Discovering the Brain by : National Academy of Sciences

Download or read book Discovering the Brain written by National Academy of Sciences and published by National Academies Press. This book was released on 1992-01-01 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain ... There is no other part of the human anatomy that is so intriguing. How does it develop and function and why does it sometimes, tragically, degenerate? The answers are complex. In Discovering the Brain, science writer Sandra Ackerman cuts through the complexity to bring this vital topic to the public. The 1990s were declared the "Decade of the Brain" by former President Bush, and the neuroscience community responded with a host of new investigations and conferences. Discovering the Brain is based on the Institute of Medicine conference, Decade of the Brain: Frontiers in Neuroscience and Brain Research. Discovering the Brain is a "field guide" to the brainâ€"an easy-to-read discussion of the brain's physical structure and where functions such as language and music appreciation lie. Ackerman examines: How electrical and chemical signals are conveyed in the brain. The mechanisms by which we see, hear, think, and pay attentionâ€"and how a "gut feeling" actually originates in the brain. Learning and memory retention, including parallels to computer memory and what they might tell us about our own mental capacity. Development of the brain throughout the life span, with a look at the aging brain. Ackerman provides an enlightening chapter on the connection between the brain's physical condition and various mental disorders and notes what progress can realistically be made toward the prevention and treatment of stroke and other ailments. Finally, she explores the potential for major advances during the "Decade of the Brain," with a look at medical imaging techniquesâ€"what various technologies can and cannot tell usâ€"and how the public and private sectors can contribute to continued advances in neuroscience. This highly readable volume will provide the public and policymakersâ€"and many scientists as wellâ€"with a helpful guide to understanding the many discoveries that are sure to be announced throughout the "Decade of the Brain."

Neuroprotection

Author : Matilde Otero-Losada
Publisher : BoD – Books on Demand
ISBN 13 : 1838804390
Total Pages : 350 pages
Book Rating : 4.8/5 (388 download)

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Book Synopsis Neuroprotection by : Matilde Otero-Losada

Download or read book Neuroprotection written by Matilde Otero-Losada and published by BoD – Books on Demand. This book was released on 2020-11-26 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurological disease affects nearly 25%–30% of the world’s population, exerting enormous financial strain on the healthcare system. Estimated current costs are around $800 annual billion, and this number is expected to increase exponentially as the global population ages. As such, new and alternative neuroprotective strategies are urgently needed. This book examines some of the most promising approaches in neuroprotection as well as discusses current goals and prospects. Organized into three sections, chapters cover such topics as the use of cannabinoids, medicinal plants, and essential oils in Alzheimer’s and Parkinson’s; protein misfolding and the neuroprotective potential of vitamin E in cerebral ischemia; and potential new neurological treatments and their mechanisms of action.

Synaptic Function

Author : Neurosciences Institute (New York, N.Y.)
Publisher : Wiley-Interscience
ISBN 13 :
Total Pages : 808 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Synaptic Function by : Neurosciences Institute (New York, N.Y.)

Download or read book Synaptic Function written by Neurosciences Institute (New York, N.Y.) and published by Wiley-Interscience. This book was released on 1987 with total page 808 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book consists of five sections. The first section details methods for analyzing both presynaptic and postsynaptic function and emphasizes the molecular aspects of synapses. It describes ongoing studies of neurotransmitter release, voltage- sensitive ion channels, and electronic transmission at gap junctions. The second section focuses on the growing menagerie of neurotransmitters: their catagorization into chemical families, their relation to ion channels, their modulation by second messenger systems and their role in pharmacologic action. The third section considers the important relationship of transmitter diversity and synaptic types to the behavior of actual cellular networks. All of the studies described in these sections point to the necessity of considering interactions between anatomy, chemistry, physiology and pharmacology if synaptic function is to be understood at any one of these levels of analysis.

Techniques to Investigate Mitochondrial Function in Neurons

Author : Stefan Strack
Publisher :
ISBN 13 : 9781493968909
Total Pages : 344 pages
Book Rating : 4.9/5 (689 download)

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Book Synopsis Techniques to Investigate Mitochondrial Function in Neurons by : Stefan Strack

Download or read book Techniques to Investigate Mitochondrial Function in Neurons written by Stefan Strack and published by . This book was released on 2017 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: "This volume describes a broad spectrum of experimental approaches for investigating structure, function, and transport of neuronal mitochondria in health and disease. Most of these approaches were only recently developed and range from electron tomography-based 3D reconstruction of mitochondrial cristae to patch clamp recording from mitochondria in intact neurons. The chapters in this book cover topics such as mitochondrial proteomics, fluorescence lifetime imaging, respirometry and mitophagy, as well as optical approaches based on the use of genetically engineered fluorescent sensors for monitoring synaptic ATP and axonal ROS generation, mitochondrial Ca2+ cycling and pH changes, and mitochondrial dynamics and axonal trafficking in live neurons. Each chapter also discusses difficulties, tips, tricks, and precautions to take. Neuromethods series style chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and comprehensive, Techniques to Investigate Mitochondrial Function in Neurons is a valuable and useful resource for a broad range of investigators interested in the function of neuronal mitochondria in health and disease states."--Publisher's description.

Brain Mitochondrial Hexokinase: a Proposed Relation Between Soluble-particulate Distribution and in Vivo Activity

Author : John E. Wilson
Publisher :
ISBN 13 :
Total Pages : 27 pages
Book Rating : 4.:/5 (227 download)

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Book Synopsis Brain Mitochondrial Hexokinase: a Proposed Relation Between Soluble-particulate Distribution and in Vivo Activity by : John E. Wilson

Download or read book Brain Mitochondrial Hexokinase: a Proposed Relation Between Soluble-particulate Distribution and in Vivo Activity written by John E. Wilson and published by . This book was released on 1968 with total page 27 pages. Available in PDF, EPUB and Kindle. Book excerpt: The paper presents observations on a number of factors influencing the binding of hexokinase by rat brain mitochondria, and describes further studies on the nature of the latent form of the enzyme. The results suggest that various metabolic intermediates, whose concentrations are known to vary with the cerebral glycolytic rate, may regulate the in vivo hexokinase activity through their effect on the soluble-particulate distribution of the enzyme, the particulate enzyme being considered the more active form. (Author).

Manipulating the Mouse Embryo

Author : Andras Nagy
Publisher : Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press
ISBN 13 :
Total Pages : 784 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Manipulating the Mouse Embryo by : Andras Nagy

Download or read book Manipulating the Mouse Embryo written by Andras Nagy and published by Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press. This book was released on 2003 with total page 784 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides background information and detailed protocols for developing a mouse colony and using the animals in transgenic and gene-targeting experiments. The protocols list the animals, equipment, and reagents required and step-by-step procedures. Topics include in vitro culture of preimplantation embryos, surgical procedures, the production of chimeras, and the analysis of genome alterations. The third edition adds protocols for cloning mice, modifying embryonic stem cells, intracytoplasmic sperm injection, and cryopreservation of embryos.

Bioenergetics of the Cell: Quantitative Aspects

Author : Valdur A. Saks
Publisher : Springer Science & Business Media
ISBN 13 : 1461556538
Total Pages : 444 pages
Book Rating : 4.4/5 (615 download)

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Book Synopsis Bioenergetics of the Cell: Quantitative Aspects by : Valdur A. Saks

Download or read book Bioenergetics of the Cell: Quantitative Aspects written by Valdur A. Saks and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume continues the discussion of the problems of in vivo and in vitro. The recently solved X-ray structure of the mitochondrial creatine kinase and its molecular biology cellular bioenergetics - the tradition we started in 1994 by publication of the focused issue of Molecular and Cellular are analyzed with respect to its molecular physiology and Biochemistry, volume 133/134 and a book 'Cellular Bio functional coupling to the adenine nucleotide translocase, as energetics: role of coupled creatine kinases' edited by V. Saks well as its participation, together with the adenylate kinase and R. Ventura-Clapier and published by Kluwer Publishers, system, in intracellular energy transfer. The results of the Dordrecht -Boston. In the present volume, use of quantitative studies of creatine kinase deficient transgenic mice are methods of studies of organized metabolic systems, such as summarized and analyzed by using mathematical models of mathematical modeling and Metabolic Control Analysis, for the compartmentalized energy transfer, thus combining two investigation of the problems of bioenergetics of the cell is powerful new methods of the research. All these results, described together with presentation of new experimental together with the physiological and NMR data on the cardiac results. The following central problems of the cellular bio metabolic and mitochondrial responses to work-load changes energetics are the focus of the discussions: the mechanisms concord to the concept of metabolic networks of energy of regulation of oxidative phosphorylation in the cells in vivo transfer and feedback regulation.

Magnesium in the Central Nervous System

Author : Robert Vink
Publisher : University of Adelaide Press
ISBN 13 : 0987073052
Total Pages : 354 pages
Book Rating : 4.9/5 (87 download)

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Book Synopsis Magnesium in the Central Nervous System by : Robert Vink

Download or read book Magnesium in the Central Nervous System written by Robert Vink and published by University of Adelaide Press. This book was released on 2011 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

The Role of Mitochondrial Dynamics on Neurodegenerative Processes of Multiple Sclerosis in Respose to Inflammation and Endoplasmic Reticulum Stress

Download The Role of Mitochondrial Dynamics on Neurodegenerative Processes of Multiple Sclerosis in Respose to Inflammation and Endoplasmic Reticulum Stress PDF Online Free

Author : Xiaodan Deng
Publisher :
ISBN 13 :
Total Pages : 119 pages
Book Rating : 4.:/5 (9 download)

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Book Synopsis The Role of Mitochondrial Dynamics on Neurodegenerative Processes of Multiple Sclerosis in Respose to Inflammation and Endoplasmic Reticulum Stress by : Xiaodan Deng

Download or read book The Role of Mitochondrial Dynamics on Neurodegenerative Processes of Multiple Sclerosis in Respose to Inflammation and Endoplasmic Reticulum Stress written by Xiaodan Deng and published by . This book was released on 2014 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biopsies and post-mortem tissue of patients with multiple sclerosis (MS) as well as inflammatory demyelinating animal models show that endoplasmic reticulum (ER) stress is a hallmark of the progression of these pathologies. Moreover, MS biopsies and animal models of neuroinflammatory diseases have detected axonal damage associated with mitochondria fragmentation and impaired distribution as an early event in absence of demyelination. It is thought that a combination of these phenomena makes cells more susceptible to inflammatory--mediated neurodegeneration and subsequent progression of the disease. Recent studies have demonstrated that Rab32, a small GTPase in the Ras protein family, plays a role in regulating mitochondrial mobility and ER stress induced apoptosis. Liang et al. showed that Rab32 expression sharply increases in response to acute brain inflammation, but subsequently drops. Based on the finding that activation of Rab32 induces ER stress related apoptosis and facilitates mitochondrial fragmentation via activation of dynamin-related protein 1 (Drp1), we hypothesize that Rab32 could play a role in altering the axonal mitochondrial distribution and inducing neurodegeneration in MS. In this study, we probed and measured the levels of Rab32 protein and functional related proteins Rab38 and Rab7L1, ER stress and apoptosis related proteins in acute as well as chronic lesions and normal-appearing white matter (NAWM) of inflamed MS brain tissues by Western blot and immunohistochemistry. Indeed, we found that high levels of Rab32 coincide with ER stress-associated apoptosis in acute lesions and its activation leads to shorter neurites with fragmented mitochondria in human neurons. Moreover, abnormal expression and activity of Rab32 accelerates apoptosis of human neurons, suggesting a role for Rab32 in neurodegenerative progression of MS.

Mitochondrial Function

Author : William S. Allison
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (639 download)

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Book Synopsis Mitochondrial Function by : William S. Allison

Download or read book Mitochondrial Function written by William S. Allison and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Mitochondrial Dynamics and Neurodegeneration

Author : Bingwei Lu
Publisher : Springer
ISBN 13 : 9789400799479
Total Pages : 0 pages
Book Rating : 4.7/5 (994 download)

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Book Synopsis Mitochondrial Dynamics and Neurodegeneration by : Bingwei Lu

Download or read book Mitochondrial Dynamics and Neurodegeneration written by Bingwei Lu and published by Springer. This book was released on 2014-10-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are essential organelles in eukaryotic cells that control such diverse processes as energy metabolism, calcium buffering, and cell death. Recent studies have revealed that changes in mitochondrial morphology by fission and fusion, a process known as mitochondrial dynamics, is particularly important for neuronal function and survival. Defects in this process are commonly found in neurodegenerative diseases, offering a new paradigm for investigating mechanisms of neurodegeneration. To provide researchers working on neurodegenerative diseases and mitochondria with updated information on this rapidly progressing field, we have invited experts in the field to critically review recent progresses and identify future research directions. The topics include genetics of mitochondrial dynamics, mitochondrial dynamics and bioenergetics, autophagy, apoptosis, and axonal transport, and its role in neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Brain Aging

Author : David R. Riddle
Publisher : CRC Press
ISBN 13 : 9781420005523
Total Pages : 408 pages
Book Rating : 4.0/5 (55 download)

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Book Synopsis Brain Aging by : David R. Riddle

Download or read book Brain Aging written by David R. Riddle and published by CRC Press. This book was released on 2007-04-19 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recognition that aging is not the accumulation of disease, but rather comprises fundamental biological processes that are amenable to experimental study, is the basis for the recent growth of experimental biogerontology. As increasingly sophisticated studies provide greater understanding of what occurs in the aging brain and how these changes occur

Mitochondrial Disorders in Neurology

Author : Anthony Henry Vernon Schapira
Publisher : Butterworth-Heinemann
ISBN 13 :
Total Pages : 272 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Mitochondrial Disorders in Neurology by : Anthony Henry Vernon Schapira

Download or read book Mitochondrial Disorders in Neurology written by Anthony Henry Vernon Schapira and published by Butterworth-Heinemann. This book was released on 1994 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondrial Disorders in Neurology provides an overview of mitochondrial diseases. This book discusses the effects of mitochondrial dysfunction based on the relevant biochemistry and molecular genetics. The abnormal muscle and mitochondrial morphology in a variety of clinical presentations from isolated ophthalmoplegia to severe encephalopathy are also elaborated. This text likewise deliberates Leber's hereditary optic neuropathy, neurodegenerative disorders, and respiratory chain defects. Other topics covered include mitochondrial DNA and the genetics of mitochondrial disease; cytochrome ox ...

Extracellular and Intracellular Signaling

Author : James D. Adams
Publisher : Royal Society of Chemistry
ISBN 13 : 1849731608
Total Pages : 319 pages
Book Rating : 4.8/5 (497 download)

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Book Synopsis Extracellular and Intracellular Signaling by : James D. Adams

Download or read book Extracellular and Intracellular Signaling written by James D. Adams and published by Royal Society of Chemistry. This book was released on 2011 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: Intracellular cell signaling is a well understood process. However, extracellular signals such as hormones, adipokines, cytokines and neurotransmitters are just as important but have been largely ignored in other works. Aimed at medical professionals and pharmaceutical specialists, this book integrates extracellular and intracellular signalling processes and offers a fresh perspective on new drug targets.

Diet and Nutrition in Dementia and Cognitive Decline

Author : Colin R Martin
Publisher : Academic Press
ISBN 13 : 0124079393
Total Pages : 1246 pages
Book Rating : 4.1/5 (24 download)

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Book Synopsis Diet and Nutrition in Dementia and Cognitive Decline by : Colin R Martin

Download or read book Diet and Nutrition in Dementia and Cognitive Decline written by Colin R Martin and published by Academic Press. This book was released on 2014-12-30 with total page 1246 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diet and Nutrition in Dementia and Cognitive Decline offers researchers and clinicians a single authoritative source which outlines the complex interrelationships between cognitive decline, dementia and the way diet can be modified to improve outcomes. In a cross-disciplinary field like dementia research and practice, clinicians and researchers need a comprehensive resource which will quickly help them identify a range of nutritional components and how they affect cognitive decline and the development of dementia. While the focus is on clinical applications, the book also features landmark and innovative preclinical studies that have served as the foundation of rigorous trials. Chapters explore the evidence of how nutritional components, either in the diet or supplements, can either impede the development to, or progression from, the onset of dementia. Authors investigate how conditions and processes overlap between defined conditions and present studies which show that dietary components may be equally effective in a number of conditions characterized by declining cognition or dementia. This book represents essential reading for researchers and practicing clinicians in nutrition, dietetics, geriatrics, nursing, neurology, and psychology, as well as researchers, such as neuroscientists, molecular and cellular biochemists, interested in dementia. http://www.acnr.co.uk/2015/07/diet-and-nutrition-in-dementia-and-cognitive-decline/ - Explores the complex interrelationships between cognitive decline, dementia and the way diet can be modified to improve outcomes - Focuses on both clinical nutrition applications and the innovative preclinical studies that serve as the foundation for rigorous trials - Covers specific conditions and mechanisms in dementias, as well as general aspects, risk factors, lifestyle and guidelines for practitioners - Organizes chapter content in terms of the molecular, mechanistic, epidemiologic, and practical, so that correlations can be observed across conditions