Peripheral Immune System And Neurodegenerative Disease

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Peripheral Immune System And Neurodegenerative Disease

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Author : Ke Zhang
language : en
Publisher: Frontiers Media SA
Release Date : 2022-09-15

Peripheral Immune System And Neurodegenerative Disease written by Ke Zhang 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 2022-09-15 with Science categories.

Peripheral Immunity In Parkinson S Disease Emerging Role And Novel Target For Therapeutics

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Author : Cristoforo Comi
language : en
Publisher: Frontiers Media SA
Release Date : 2019-12-23

Peripheral Immunity In Parkinson S Disease Emerging Role And Novel Target For Therapeutics written by Cristoforo Comi 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 2019-12-23 with categories.

Microglia And Beyond

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Author :
language : en
Publisher:
Release Date : 2023

Microglia And Beyond written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023 with categories.

Summary This thesis describes multiple central and peripheral immune cell changes during aging, in Alzheimer’s disease (AD), and multiple sclerosis (MS). In the first chapters of this thesis, we investigated the effect of aging on the immune system and searched for the aging factors involved. In the later chapters, we investigated the immune response to AD and MS pathology. Aging During aging, a general decline in immune function occurs, ultimately contributing to increased susceptibility to infections in the elderly. We found that microglial morphological complexity declines during aging and can be modulated by peripheral levels of glucocorticoids. We further discovered that peripheral factors can induce age-associated changes in the brain, and thus potentially counteract them. Consequently, we hypothesize that modulating peripheral immunity via plasma factors, such as hormones and cytokines, could combat brain aging and associated pathology. Alzheimer’s disease AD is a neurodegenerative disease that ultimately causes dementia. One of the pathological hallmarks is the deposition of abnormal tau protein in the brain. We found that this deposition induced reactive and dystrophic microglia with increased lysosomal volumes containing abnormal tau and postsynaptic structures. Together, this shows that tauopathy induces a loss of homeostatic microglia that is potentially linked to a loss of synapses. Peripheral immune cells are associated with neurodegenerative diseases as well, although fewer research attempts have investigated these cells in the context of AD. We analyzed the peripheral immune landscape of AD patients at the early and late stages of the disease and found that levels of circulating CD8+ T cells with an effector memory phenotype increased before the onset of dementia. These CD8+ T cells expressed markers associated with T cell senescence and terminal differentiation.

Understanding The Changes In Systemic Immunity In The Neurodegenerative Disorders Frontotemporal Dementia And Alzeimers Disease

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Author : Trisha Stan
language : en
Publisher:
Release Date : 2014

Understanding The Changes In Systemic Immunity In The Neurodegenerative Disorders Frontotemporal Dementia And Alzeimers Disease written by Trisha Stan and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.

From their earliest histopathological descriptions, neurodegenerative disorders have been known to involve neuroinflammation. Yet the exact nature of the changes in inflammation, as well as the role of neuroinflammation in the pathogenesis of the disease, are not well understood. In this dissertation, I attempt to uncover the nature of the changes in the systemic immune system in neurodegeneration and the role that these changes play in disease progression. The first study presented here (Chapter 2) presents an investigation of the changes in the plasma cytokines and peripheral immune cells in Frontotemporal Dementia. Frontotemporal Dementia is the leading cause of early-onset neurodegenerative disease and is known to be caused by several mutations, including one that results in haploinsufficiency of progranulin, a gene known to attenuate inflammation. However, Frontotemporal Dementia is often sporadic, with no known genetic or environmental cause, and the underlying changes that cause this very specific, localized neurodegeneration has been unclear. In this study, we use an unbiased protein profiling platform, the antibody microarray, developed in our lab, to assay the changes in plasma protein levels in progranulin-mutation Frontotemporal Dementia and sporadic Frontotemporal Dementia. We found that there was an increase in pro-inflammatory cytokines similar to changes in cytokines observed in autoimmune disease and suggestive of changes in cellular immune phenotype. Therefore, we used a new flow cytometry technology, CyTOF by Time of Flight mass spectrometry (CyTOF), to profile immune cells in FTD patients in an unbiased manner. We found changes in CD8 T cells and Natural Killer cells similar to changes observed in autoimmune disorders. Along with colleagues at UCSF, we then conducted a retrospective study to determine if FTD patients have a higher comorbidity of autoimmune disease than the general population, and we found this to be the case. We found similar changes in inflammatory proteins and immune cells in the mouse model of Frontotemporal Dementia (GRN -/- ). The next series of experiments (Chapter 3) sought to determine how the changes in the systemic protein levels in the plasma FTD patients affected the changes in the central nervous system (CNS) associated with the neurodegenerative disorders and with the changes in immune cell populations. To this end, we used two methods of introducing FTD-disease plasma to WT or GRN +/- mice: parabiosis and human plasma transfer. While we observed no changes in the strongest phenotype of the mouse model, microgliosis, in the parabiosis experiment, we observed intriguing behavior changes in GRN +/- animals treated with plasma from human FTD patients. For the next set of experiments to determine the relationship between the cytokine changes in FTD patients and the immune cell subset changes, we developed a new culture system in which we cultured whole blood with plasma-infused media, enabling us to use cells from a single donor to assay the effects of exposure of aged or FTD-patient plasma. In the final series of experiments, we sought to solidify the understanding of the changes in the systemic immune system in Alzheimer's Disease with a thorough immunophenotyping study. For four years, we collected and cryopreserved peripherial blood mononuclear cells from Alzheimer's Disease patients, resulting in a collection of over 100 samples from patients with mild to sever Alzheimer's Disease, patients with Mild Cognitive Impairment, a precursor to Alzheimer's Disease, and age-matched, cognitively healthy individuals. We developed a new CyTOF platform panel to measure the ability of cells to respond to cytokine treatment as well as the traditional immunophenotyping. We found indications that cells from Alzheimer's Disease patients are less responsive to cytokine stimuli. Collectively, this work highlights the importance of the changes in the systemic immune system in neurodegenerative disorders. It provides new insight into possible mechanisms of disease pathology and potential new avenues for future therapeutic targets.

Neuro Immune Interactions In Neurologic And Psychiatric Disorders

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Author : P. Patterson
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06

Neuro Immune Interactions In Neurologic And Psychiatric Disorders written by P. Patterson 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 2012-12-06 with Medical categories.

The idea that the brain is an "immune-privileged site" has perhaps served to slow our realization that the intact brain can generate its own inflammatory reactions. These responses can be to peripheral infection, or they can arise from local, internal causes, for instance as a response to stress or to the se vere changes in neuronal activity in seizure or the loss of oxygen in stroke. We are also becoming increasingly aware of the contribution of local inflam matory reactions to certain neurodegenerative diseases such as Alzheimer's In fact, evidence is accumulating that inflammatory processes disease (AD). contribute to the progression of AD, suggesting the possibility of using cur rently available or novel anti-inflammatory agents to interfere with this terri ble disease. Correlations are also being made between inflammatory signs and mental illness, which is a new frontier of research. This book presents the current state of knowledge in a variety of areas relevant to neuro-immune interactions, with particular attention to AD.

Crosstalk Between Peripheral And Local Immune Response In The Pathophysiology Of Stroke And Neurodegeneration Diseases Volume Ii

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Author : Yuanjian Fang
language : en
Publisher: Frontiers Media SA
Release Date : 2024-03-06

Crosstalk Between Peripheral And Local Immune Response In The Pathophysiology Of Stroke And Neurodegeneration Diseases Volume Ii written by Yuanjian Fang 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 2024-03-06 with Medical categories.

Accumulating evidence reveals both local and peripheral immune systems participated in the pathophysiology changes of acute and chronic neurological diseases. Immune cell activation facilitates inflammatory response in neurological diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. The immune response initiated by brain local cells (microglia and astrocytes) and peripheral blood cells (monocytes/macrophages, neutrophil, T cells, B cells), are now commonly thought to contribute “double-edged sword” effects to the progression of neurological diseases, which not only promoting repair and recovery, but also accelerating brain injury. Meanwhile, local and peripheral immune responses have complex crosstalk in the development of post-stroke injury and neurodegeneration disease.

Crosstalk Between Peripheral And Local Immune Response In The Pathophysiology Of Stroke And Neurodegeneration Diseases

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Author : Yuanjian Fang
language : en
Publisher: Frontiers Media SA
Release Date : 2023-12-27

Crosstalk Between Peripheral And Local Immune Response In The Pathophysiology Of Stroke And Neurodegeneration Diseases written by Yuanjian Fang 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 2023-12-27 with Medical categories.

Neuroimmune Pharmacology

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Author : Tsuneya Ikezu
language : en
Publisher: Springer
Release Date : 2016-12-22

Neuroimmune Pharmacology written by Tsuneya Ikezu and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-12-22 with Medical categories.

The second edition of Neuroimmune Pharmacology bridges the disciplines of neuroscience, immunology and pharmacology from the molecular to clinical levels with particular thought made to engage new research directives and clinical modalities. Bringing together the foremost field authorities from around the world, Neuroimmune Pharmacology will serve as an invaluable resource for the basic and applied scientists of the current decade and beyond.

Clinical Relevance Of The Immune To Brain And Brain To Immune Communications

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Author : Julie Lasselin
language : en
Publisher: Frontiers Media SA
Release Date : 2019-03-29

Clinical Relevance Of The Immune To Brain And Brain To Immune Communications written by Julie Lasselin 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 2019-03-29 with categories.

Experimental and clinical evidence demonstrates an intense crosstalk among the nervous, endocrine and immune systems. The central nervous system (CNS) not only has the capacity to affect peripheral immune function, but is also able to sense and process signals from the peripheral immune system. The bi-directional interaction between the CNS and the peripheral immune system has gained great interest as it can help better understand disease pathophysiology as well as improving health and treatment outcomes in patients. On the one hand, inflammatory factors are known to affect CNS functions and to induce neuropsychiatric symptoms, making immune-to-brain communication highly relevant for psychiatric diseases and their treatments. On the other hand, analyzing pathways of brain-to-immune communication will help to understand the pathophysiology of chronic inflammatory disorders and will form the basis for optimizing treatment of these diseases.

Immune Responses In The Nervous System

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Author : Nancy Rothwell
language : en
Publisher: Taylor & Francis
Release Date : 1995

Immune Responses In The Nervous System written by Nancy Rothwell and has been published by Taylor & Francis this book supported file pdf, txt, epub, kindle and other format this book has been release on 1995 with Medical categories.

Many molecules and mechanisms traditionally associated with the peripheral immune system have been found to be active within the central nervous system. The investigation of immune activation is a rapidly expanding field of research, particularly since it is directly related to acute neuronal damage and in degenerative disorders of the nervous system such as Alzheimer's disease and multiple sclerosis. This volume brings together a team of internationally recognized experts who address topics such as neuronal transplantation, leukocyte migration, the role of inflammation and immune responses in neurological diseases and brain injury, and the potential benefits of treatment with modulators of cytokine action. It will be of interest to all researchers and clinicians involved in the understanding, diagnosis and treatment of neuroimmune diseases.