The Role Of Tumor Necrosis Factor Alpha In A Prodromal Mouse Model Of Alzheimer S Disease
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The Role Of Tumor Necrosis Factor Alpha In A Prodromal Mouse Model Of Alzheimer S Disease
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Author : Chelsea Cavanagh
language : en
Publisher:
Release Date : 2016
The Role Of Tumor Necrosis Factor Alpha In A Prodromal Mouse Model Of Alzheimer S Disease written by Chelsea Cavanagh and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
"Since the advanced stages of Alzheimer's disease (AD) have proven to be difficult to treat, investigating ways to prevent AD has become a priority for the research community. Although neuroinflammation is commonly associated with amyloid plaque deposits and neurodegeneration that are characteristic of advanced stages, emerging evidence suggests that inflammatory mediators may play a role in the early development of AD pathology. Importantly, inflammatory mediators such as the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), have important effects modulating synaptic function. Therefore, TgCRND8 mice, which overexpress a mutated form of the human amyloid precursor protein, were investigated at a prodromal stage to study whether TNF-alpha may be contributing to alterations in synaptic function and precipitating alterations in cognitive performance.Western blot and ELISA experiments indicated a significant increase in hippocampal TNF-alpha expression in 1-month-old TgCRND8 mice before plaque deposition that correlated with levels of the Beta-C-terminal fragment, the precursor to amyloid-beta. Cluster of differentiation 11b labeling indicated changes in microglial morphology toward an activated state, suggesting that these cells may be a putative source of the observed TNF-alpha increase during this prodromal stage of AD-like pathology. While TNF-alpha is recognized for its role in the immune system, this cytokine has neuromodulatory actions as well and modulates the insertion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in synapses to increase glutamatergic transmission under conditions of low activity. Therefore, the pre-plaque increase in TNF-alpha may affect transmission at glutamate synapses and precipitate synaptic pathologies. To test the hypothesis that TNF-alpha is contributing to hyperexcitability of glutamate synapses and alterations in cognitive function, hippocampal synaptic and cognitive function were compared between TgCRND8 mice and control littermates at the 1-month time point and the effects of a soluble dominant-negative TNF-alpha inhibitor, XPro1595, were examined. Pre-plaque TgCRND8 mice exhibited increased basal synaptic function and long-term potentiation that were reversed by XPro1595 treatment. In vivo XPro1595 treatment also reversed the enhanced performance of 1-month-old TgCRND8 mice in a hippocampus-dependent inhibitory avoidance task. Although synaptic deficits are commonly found in animal models of amyloidosis, it is unclear how amyloid pathology may impair synaptic function. In some amyloid mouse models of AD, however, synaptic deficits are preceded by hyperexcitability of glutamate synapses. To study whether the early TNF-alpha-associated enhancement of glutamatergic transmission was responsible for the development of later synaptic deficits 1-month-old TgCRND8 mice were treated for 4 weeks with XPro1595. This targeted treatment prevented deficits in basal glutamatergic transmission otherwise apparent at age 6 months. These findings suggest that the increase in TNF-alpha before amyloid plaque formation could be an early process leading to the hyperexcitability of glutamate synapses, which leads to alterations in cognitive function. In this mouse model at least, reversing the hyperexcitability of glutamate synapses via TNF-alpha blockade before the onset of amyloid plaque formation prevented later synaptic deficits. " --
The Effects Of Tumor Necrosis Factor Alpha On Striatal Synapses In The Yac128 Mouse Model Of Huntington S Disease
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Author : Julien Chambon
language : en
Publisher:
Release Date : 2020
The Effects Of Tumor Necrosis Factor Alpha On Striatal Synapses In The Yac128 Mouse Model Of Huntington S Disease written by Julien Chambon and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with categories.
"Huntington’s disease is a late-onset neurodegenerative disease, characterized by various motor and neuronal deficits. To this day, the disease is ultimately fatal and treatments only focus on symptom management. The disease stems from an expansion of the CAG repeats on the huntingtin gene, creating an overly large and likely misfolded mutant huntingtin protein. However, it is still unclear how the mutant huntingtin leads to neurodegeneration or symptom development. One theory states that the immune system is involved in disease development. It was observed in patients and mouse models of the disease that both the peripheral and CNS-specific immune system seems to be overly active, even before the onset of symptoms, indicating that the immune system may have a role in Huntington’s disease development. Specifically, we are interested in the potential role of the cytokine tumor necrosis factor (TNF) in disease development. In the CNS, TNF is linked with homeostatic synaptic plasticity, and specifically the trafficking of AMPA receptors in or out of the synaptic surface. Interestingly, many studies have shown that TNF inhibition has therapeutic effects in mouse models, and that homeostatic synaptic plasticity is impaired in Huntington’s disease, which could link TNF to the disease development. More specifically, TNF could be involved in excitotoxicity, since it preferentially targets calcium-permeable AMPA receptors.Therefore, we hypothesized that in pre-symptomatic Huntington’s disease, the role of TNF in homeostatic synaptic plasticity is dysregulated, leading to an increased exocytosis of calcium-permeable AMPA receptors at the synaptic surface. From our results, we had two main conclusions. First, the concentration of TNF has drastic changes on its effects on striatal neurons, with higher concentrations leading to more excitable neurons, and lower concentrations more inhibited neurons. Secondly, there is a TNF-dependent change in synaptic strength and inhibitory synapses in pre-symptomatic Huntington’s mouse model, indicative that TNF is involved in HD development"--
Drebrin
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Author : Tomoaki Shirao
language : en
Publisher: Springer
Release Date : 2018-08-22
Drebrin written by Tomoaki Shirao and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-08-22 with Medical categories.
This book is the first comprehensive review of drebrin, which plays pivotal roles in various cellular events, via forming unique actin cytoskeletons, including synapse formation and in synaptic function. Particularly the loss of drebrin from dendritic spines is used as a marker of dementia in neurological disorders such as Alzheimer’s disease. Since drebrin was first identified by our group in 1985, many studies of drebrin have been done in various fields, including not only molecular biology, biophysics, cell biology, neuroscience, clinical studies, spermatogenesis, immunology, and cancer metastasis, but others as well. The structure of this book facilitates the understanding of the whole picture of studies on drebrin. The volume begins with a general introduction to drebrin, and then the chapters in the second part provide the basic knowledge for further understanding. The third part examines its function in the nervous system, and the fourth part discusses its function in the non-nervous system. This work will appeal to researchers who are interested in cytoskeletal dynamics at membrane-cytoskeletal interface as well as the number of them who use drebrin as a tool, such as a marker of synaptic function or a disease marker. This volume is kept as concise as possible in order to be understood by readers in diverse scientific disciplines.
Handbook Of The Biology Of Aging
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Author : Caleb Finch
language : en
Publisher:
Release Date : 1977
Handbook Of The Biology Of Aging written by Caleb Finch and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1977 with Medical categories.
Metabolism In Alzheimer S Disease
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Author : Heather M. Wilkins
language : en
Publisher: Frontiers Media SA
Release Date : 2022-02-11
Metabolism In Alzheimer S Disease written by Heather M. Wilkins and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-02-11 with Science categories.
Molecular Neurology
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Author : Stephen Waxman
language : en
Publisher: Elsevier
Release Date : 2010-07-26
Molecular Neurology written by Stephen Waxman and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-07-26 with Medical categories.
Why a book on molecular neurology? Molecular neuroscience is advancing at a spectacular rate. As it does so, it is revealing important clues to the pathogenesis and pathophysiology of neurological diseases, and to the therapeutic targets that they present. Medicines work by targeting molecules. The more specific the targeting, the more specific the actions, and the fewer the side effects. Molecular Neurology highlights, for graduate and MD-PhD students, research fellows and research-oriented clinical fellows, and researchers in the neurosciences and other biomedical sciences, the principles underlying molecular medicine as related to neurology. Written by internationally recognized experts, this well-illustrated and well-referenced book presents the most up-to-date principles and disease examples relevant to molecular neurology, and reviews the concepts, strategies, and latest progress in this field. This book will interest anyone studying the molecular basis of neurology, or developing new therapies in neurology. Describes the newest molecular aspects of neurological disorders Provides an introduction to neurological disorders for basic scientists Updates clinicians and clinical researchers on the most recent developments
Mechanisms Of Neuroinflammation
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Author : Gonzalo Emiliano Aranda Abreu
language : en
Publisher: BoD – Books on Demand
Release Date : 2017-08-23
Mechanisms Of Neuroinflammation written by Gonzalo Emiliano Aranda Abreu and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-23 with Medical categories.
"Mechanisms of Neuroinflammation" book explains how the neuronal cells become swollen at the moment of the blood-brain barrier disruption and how they lose their immunological isolation. A cascade of cytokines and immune cells from the bloodstream enters the nervous system, inflaming neurons and activating the glia. This produces a neuroinflammatory process that can generate different neurodegenerative diseases. Better understanding of mechanisms that are activated at the time when the damage to the brain occurs could lead to the development of suitable therapies that revert the neuronal inflammation and thus prevent further damage to the nervous system.
Tau Oligomers
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Author : Jesus Avila
language : en
Publisher: Frontiers E-books
Release Date : 2014-08-18
Tau Oligomers written by Jesus Avila and has been published by Frontiers E-books this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-08-18 with Medicine (General) categories.
Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.
Neuroglia In Neurodegenerative Diseases
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Author : Alexei Verkhratsky
language : en
Publisher: Springer Nature
Release Date : 2019-10-03
Neuroglia In Neurodegenerative Diseases written by Alexei Verkhratsky and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-10-03 with Medical categories.
This book provides a comprehensive overview of the role of neuroglia in neurodegenerative diseases. Neuroglia are the most abundant cells in the nervous system and consist of several distinct cell types, such as astrocytes, oligodendrocytes,and microglia. Accumulating evidence suggests that neuroglia participate in the neurodegenerative process, and as such are essential players in a variety of diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. Intended for researchers and students, the book presents recent advances concerning the biology of neuroglia as well as their interaction with neurons during disease progression. In addition, to highlight the function of neuroglia in different types of neurodegenerative disease, it also discusses their mechanisms and effects on protecting or damaging neurons.
Alzheimer S And Parkinson S Diseases
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Author : Israel Hanin
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-06-29
Alzheimer S And Parkinson S Diseases written by Israel Hanin and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-06-29 with Medical categories.
This book represents the third in a series of International Conferences related to Alzheimer's (AD) and Parkinson's (PD) diseases. The first one took place in Eilat, Israel, in 1985; and the second one in Kyoto, Japan, in 1989. This book contains the full text of oral and poster presentations from the Third International Conference on Alzheimer's and Parkinson's Diseases: Recent Developments, held in Chicago, Illinois, U.S.A. on November 1-6, 1993. The Chicago Conference was attended by 270 participants. The Scientific Program was divided into nine oral sessions, a keynote presentation, and a poster session. The conference culminated in a Round Table Discussion involving all of the participants in the conference. The four and one-half day meeting served as an excellent medium for surveying the current status of clinical and preclinical developments in AD and PD. There were 59 oral presentations and 93 posters. This book incorporates a majority of both.