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Author: Jason Knight Clark
Publisher:
ISBN:
Category :
Languages : en
Pages : 546
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Book Description
Alzheimer's disease (AD) is a neurodegenerative disease of aging thought to be initiated by production of Amyloid-[beta] peptide, which leads to synaptic dysfunction and progressive memory loss, and the eventual formation of [beta]-Amyloid plaques and neurofibrillary Tau tangles. Working memory is one of the first cognitive impairments in AD. We therefore wanted to explore the cellular mechanisms underlying working memory impairments in AD utilizing a well-known triple transgenic mouse model of Alzheimer's disease (3xTg-AD) carrying mutations in APP, PS1, and Tau. We evaluated working memory using an 8-arm radial maze, and synaptic transmission and plasticity using an ex vivo hippocampal slice preparation to measure field Excitatory Post-Synaptic Potentials (fEPSP) in the CA1 region of ventral hippocampus. Unexpectedly, young 3xTg-AD mice at 3 months of age, typically considered to be presymptomatic, were significantly impaired in the spatial working memory task compared to Nontransgenic (NonTg) control mice. Measurements of fEPSPs to evaluate Long-Term Potentiation (LTP) as an indicator of long-term synaptic plasticity showed the NMDA receptor-dependent component of LTP (NMDAR LTP) was reduced in 3xTg-AD mice compared to NonTg mice. The remaining non-NMDA receptor-dependent component of LTP (non-NMDAR LTP) however was increased, resulting in a total LTP that was not different between 3xTg-AD and NonTg mice. At 8 months of age, 3xTg-AD mice were again significantly impaired in the spatial working memory task, and NMDAR LTP was again reduced in 3xTg-AD mice. The non-NMDAR LTP however was also reduced in 3xTg-AD mice, resulting in a total LTP that was now reduced in 3xTg-AD mice. The majority (>90%) of non-NMDAR LTP is mediated by Voltage-Dependent Calcium Channels (VDCC), and attempts to block LTP using NMDAR and VDCC antagonists were unsuccessful, indicating 3xTg-AD mice have compensatory mechanisms for LTP expression that occur independently of NMDAR or non-NMDAR dependent mechanisms. In addition, 3xTg-AD mice also showed impairments in short-term synaptic plasticity and basal synaptic transmission at both 3 and 8 months of age. These impairments in synaptic transmission and plasticity coincide with impairments in spatial working memory, and understanding the nature of these altered mechanisms may lead to therapeutic targets for disorders such as AD.
Author: Jason Knight Clark
Publisher:
ISBN:
Category :
Languages : en
Pages : 546
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Book Description
Alzheimer's disease (AD) is a neurodegenerative disease of aging thought to be initiated by production of Amyloid-[beta] peptide, which leads to synaptic dysfunction and progressive memory loss, and the eventual formation of [beta]-Amyloid plaques and neurofibrillary Tau tangles. Working memory is one of the first cognitive impairments in AD. We therefore wanted to explore the cellular mechanisms underlying working memory impairments in AD utilizing a well-known triple transgenic mouse model of Alzheimer's disease (3xTg-AD) carrying mutations in APP, PS1, and Tau. We evaluated working memory using an 8-arm radial maze, and synaptic transmission and plasticity using an ex vivo hippocampal slice preparation to measure field Excitatory Post-Synaptic Potentials (fEPSP) in the CA1 region of ventral hippocampus. Unexpectedly, young 3xTg-AD mice at 3 months of age, typically considered to be presymptomatic, were significantly impaired in the spatial working memory task compared to Nontransgenic (NonTg) control mice. Measurements of fEPSPs to evaluate Long-Term Potentiation (LTP) as an indicator of long-term synaptic plasticity showed the NMDA receptor-dependent component of LTP (NMDAR LTP) was reduced in 3xTg-AD mice compared to NonTg mice. The remaining non-NMDA receptor-dependent component of LTP (non-NMDAR LTP) however was increased, resulting in a total LTP that was not different between 3xTg-AD and NonTg mice. At 8 months of age, 3xTg-AD mice were again significantly impaired in the spatial working memory task, and NMDAR LTP was again reduced in 3xTg-AD mice. The non-NMDAR LTP however was also reduced in 3xTg-AD mice, resulting in a total LTP that was now reduced in 3xTg-AD mice. The majority (>90%) of non-NMDAR LTP is mediated by Voltage-Dependent Calcium Channels (VDCC), and attempts to block LTP using NMDAR and VDCC antagonists were unsuccessful, indicating 3xTg-AD mice have compensatory mechanisms for LTP expression that occur independently of NMDAR or non-NMDAR dependent mechanisms. In addition, 3xTg-AD mice also showed impairments in short-term synaptic plasticity and basal synaptic transmission at both 3 and 8 months of age. These impairments in synaptic transmission and plasticity coincide with impairments in spatial working memory, and understanding the nature of these altered mechanisms may lead to therapeutic targets for disorders such as AD.
Author: Gong-Ping Liu
Publisher: Frontiers Media SA
ISBN: 2889744841
Category : Science
Languages : en
Pages : 147
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Book Description
Author: Edward D. Levin
Publisher: CRC Press
ISBN: 1420004336
Category : Medical
Languages : en
Pages : 395
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Book Description
The costs associated with a drug's clinical trials are so significant that it has become necessary to validate both its safety and efficacy in animal models prior to the continued study of the drug in humans. Featuring contributions from distinguished researchers in the field of cognitive therapy research, Animal Models of Cognitive Impairmen
![Effect of [beta]-Amyloid on Synaptic Plasticity and Learning Processes PDF](https://books.google.com/books/content/images/frontcover/jo5_AQAACAAJ?fife=w80-h100)
Author: Simon Marcel Gengler
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Alzheimer's disease (AD) is characterised by memory impairments and the occurrence of neuronal depositions of [beta]-Amyloid. Transgenic mouse models expressing mutated genes found in inherited forms of AD have been engineered as tool to test AD medication. Therefore it is crucial to characterise the onset and nature of memory impairments and underlying synaptic dysfunction in AD mouse models. In this study, memory and synaptic function of the APPPSI-21 mouse model was analysed with behavioural tests and field potential recordings from CA3-CAl-synapses in vivo. In the water maze, APPPSI-21 mice showed impairments in spatial reference memory at the age of 6, 12 and 15 months, revealed decreased alternations in the T-Maze at 8 and 15 months of age and showed perseveration at 14 to 15 months of age in a habit reversal task. It was concluded that APPPSI-21 mice have impaired short term spatial memory at least from 6 months of age onwards, and impaired mental flexibility starting between 5 and 8 months of age. Synaptic function of APPPSI-21 mice was tested at the ages of 4.5, 6, 8, and 15 months. Potentiation of the field potential was found to be increased at 6 months and decreased at 15 months of age, suggesting altered synaptic function in APPPSI-21 mice starting between 4.5 and 6 months of age. The potential beneficial effects of Val(8)GLP-l-treatment on AD pathology was tested in 17 month old wild type and APPPSI-21 mice, that were injected daily with 25 nmol Val(8)GLP- l/kg for 21 days. This treatment resulted in improved potentiation of the field potential in wild type, but not in APPPSI-21 mice. Val(8)GLP-l-treatment decreased fibrillar [beta]-Amyloid in the cortex of APPPSI-21 mice, when stained with Congo red. These results suggest that Val(8)GLP-l-treatment may be able to inhibit depositioning of [beta]- Amyloid in brains that suffer from amyloidosis.
Author: Victor Chaban
Publisher: BoD – Books on Demand
ISBN: 1789231949
Category : Medical
Languages : en
Pages : 206
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Book Description
This book provides comprehensive and up-to-date insights into emerging research trends on neuroplasticity with current or future treatments for neurodevelopment and neurodegenerative diseases. The authors discuss structural and functional changes associated with cortical remapping, sensory substitution, synaptic and non-synaptic compensatory plasticity due to brain damage, brain training, chronic pain, meditation, music, exercise and related states. Key features include pathogenesis, and existing and new therapies together with a pharmacological and non-pharmacological approach in clinical treatment and management. The authors are established experts that contributed significantly to a better understanding of the etiology of neuroplasticity. This book is recommended to healthcare providers, clinical scientists, students and patients.
Author: Silvia Alboni
Publisher: Frontiers Media SA
ISBN: 2889197689
Category : Neurosciences. Biological psychiatry. Neuropsychiatry
Languages : en
Pages : 160
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Book Description
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-α, interleukin (IL)-1β, 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
Author: J. David Sweatt
Publisher: Academic Press
ISBN: 0080959199
Category : Psychology
Languages : en
Pages : 362
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Book Description
This fully revised second edition provides the only unified synthesis of available information concerning the mechanisms of higher-order memory formation. It spans the range from learning theory, to human and animal behavioral learning models, to cellular physiology and biochemistry. It is unique in its incorporation of chapters on memory disorders, tying in these clinically important syndromes with the basic science of synaptic plasticity and memory mechanisms. It also covers cutting-edge approaches such as the use of genetically engineered animals in studies of memory and memory diseases. Written in an engaging and easily readable style and extensively illustrated with many new, full-color figures to help explain key concepts, this book demystifies the complexities of memory and deepens the reader’s understanding. More than 25% new content, particularly expanding the scope to include new findings in translational research. Unique in its depth of coverage of molecular and cellular mechanisms Extensive cross-referencing to Comprehensive Learning and Memory Discusses clinically relevant memory disorders in the context of modern molecular research and includes numerous practical examples
Author: Fereshteh S. Nugent
Publisher: Frontiers Media SA
ISBN: 2832524346
Category : Science
Languages : en
Pages : 113
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Book Description
Author: Dalya Cohen
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Alzheimer's Disease (AD) is a physiologically devastating form of dementia, yet an understanding of AD pathology remains elusive. One promising avenue of research is to examine synaptic plasticity within the brain centres of learning and memory in animal models of AD. Long-term potentiation (LTP) is a model of learning and memory at the synaptic level, and deficits in LTP have been proposed in AD. The aim of this work is to examine whether synaptic defects in AD involve a neuronal signalling cascade: the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. This research uses novel modes of LTP induction which manipulate the course of LTP induction. Examinations reveal alterations in basal synaptic transmission in AD mouse models. The use of a cAMP/PKA enhancing drug revealed a potential dysregulation in the cAMP/PKA cascade. Lastly, coastline analysis showed potentiation induced hyperexcitability at synapses of an AD mouse model.
Author: Stefanie Poll
Publisher:
ISBN:
Category : Alzheimer's disease
Languages : en
Pages :
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Book Description
