scholarly journals Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease

2019 ◽  
Author(s):  
Sebastian Werneburg ◽  
Jonathan Jung ◽  
Rejani B. Kunjamma ◽  
Seung-Kwon Ha ◽  
Nicholas J. Luciano ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Neuronal Degeneration ◽  
Striking Similarity ◽  
Gene Therapy Approach ◽  
Synapse Loss ◽  
Complement Component C3 ◽  
Axon Loss ◽  
The Central Nervous System

SummaryMultiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. While work has focused on axon loss in MS, far less is known about synaptic changes. Here, in striking similarity to other neurodegenerative diseases, we identify in postmortem human MS tissue and in nonhuman primate and mouse MS models profound synapse loss and microglial synaptic engulfment. These events can occur independently of local demyelination, neuronal degeneration, and peripheral immune cell infiltration, but coincide with gliosis and increased localization of complement component C3, but not C1q, at synapses. Finally, we use AAV9 to overexpress the complement inhibitor Crry at activated C3-bound synapses in mice and demonstrate robust protection of synapses and visual function. These results mechanistically dissect synapse loss as an early pathology in MS. We further provide a novel gene therapy approach to prevent synapse loss by microglia, which may be broadly applicable to other neurodegenerative diseases.

scholarly journals Adiponectin Role in Neurodegenerative Diseases: Focus on Nutrition Review

2020 ◽  
Vol 21 (23) ◽  
pp. 9255
Author(s):  
Rita Polito ◽  
Irene Di Meo ◽  
Michelangela Barbieri ◽  
Aurora Daniele ◽  
Giuseppe Paolisso ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
The Central Nervous System ◽  
Regulatory Effects ◽  
Nutrition Review ◽  
Selective Process

Adiponectin is an adipokine produced by adipose tissue. It has numerous beneficial effects. In particular, it improves metabolic effects and glucose homeostasis, lipid profile, and is involved in the regulation of cytokine profile and immune cell production, having anti-inflammatory and immune-regulatory effects. Adiponectin’s role is already known in immune diseases and also in neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are a set of diseases of the central nervous system, characterized by a chronic and selective process of neuron cell death, which occurs mainly in relation to oxidative stress and neuroinflammation. Lifestyle is able to influence the development of these diseases. In particular, unhealthy nutrition on gut microbiota, influences its composition and predisposition to develop many diseases such as neurodegenerative diseases, given the importance of the “gut-brain” axis. There is a strong interplay between Adiponectin, gut microbiota, and brain-gut axis. For these reasons, a healthy diet composed of healthy nutrients such as probiotics, prebiotics, polyphenols, can prevent many metabolic and inflammatory diseases such as neurodegenerative diseases and obesity. The special Adiponectin role should be taken into account also, in order to be able to use this component as a therapeutic molecule.

Multiple Sclerosis Relapsing Remitting Progressive Type

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
Nora Fitri ◽  
Basjiruddin Ahmad ◽  
Yuliarni Syafrita
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Brain Mri ◽  
Clinical Findings ◽  
Blurred Vision ◽  
System A ◽  
Progressive Type ◽  
Relapsing Remitting ◽  
The Central Nervous System

Multiple sclerosis (MS) is the most common neurologic demyelinating disease in high-income countries. The causes of MS is multifactorial involve genetics and the environment in which immune cell infiltration occurs across the blood-brain barrier, causing inflammation, demyelination, gliosis, and neuroaxonal degeneration in the substantia grisea in the central nervous system. A 23-year-old female patient was treated with four limbs weakened since 2 weeks ago accompanied by blurred vision, pain, cramps and stiffness in the back muscles and legs. The patient has experienced the same complaint before. Clinical findings reveal lhermitte sign, atrophy papillae, and tetraparese. On thoracic vertebral MRI examination without contrast and brain MRI with contrast obtained multiple sclerosis lesions. Patients receive steroid and antidepressant therapy. MS needs to be studied further because this number of cases began to emerge. 

scholarly journals CD154 Blockade Results in Transient Reduction in Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease

2003 ◽  
Vol 77 (3) ◽  
pp. 2247-2250 ◽  
Author(s):  
Laurence M. Howard ◽  
Katherine L. Neville ◽  
Lia M. Haynes ◽  
Mauro C. Dal Canto ◽  
Stephen D. Miller
Keyword(s):  
Central Nervous System ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Immune Cell Infiltration ◽  
Theiler's Murine Encephalomyelitis Virus ◽  
Viral Loads ◽  
Theiler’S Murine Encephalomyelitis Virus ◽  
Cell Responses ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System

ABSTRACT Transient CD154 blockade at the onset of Theiler's murine encephalomyelitis virus-induced demyelinating disease ameliorated disease progression for 80 days, reduced immune cell infiltration, and transiently increased viral loads in the central nervous system. Peripheral antiviral and autoimmune T-cell responses were normal, and disease severity returned to control levels by day 120.

scholarly journals Increased Levels of IL-16 in the Central Nervous System during Neuroinflammation Are Associated with Infiltrating Immune Cells and Resident Glial Cells

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 472
Author(s):  
Shehla U Hridi ◽  
Mark Barbour ◽  
Chelsey Wilson ◽  
Aimee JPM Franssen ◽  
Tanith Harte ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cells ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Autoimmune Encephalomyelitis ◽  
Cellular Source ◽  
The Central Nervous System ◽  
Phosphate Buffered Saline ◽  
Brain And Spinal Cord

Interleukin (IL)-16, a CD4+ immune cell specific chemoattractant cytokine, has been shown to be involved in the development of multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). While immune cells such as T cells and macrophages are reported to be the producers of IL-16, the cellular source of IL-16 in the CNS is less clear. This study investigates the correlation of IL-16 expression levels in the CNS with the severity of neuroinflammation and determines the phenotype of cells which produce IL-16 in the CNS of experimental autoimmune encephalomyelitis (EAE) mice. Our data show that IL-16 expression is significantly increased in the brain and spinal cord tissues of EAE mice compared to phosphate buffered saline (PBS) immunised controls. Dual immunofluorescence staining reveals that the significantly increased IL-16+ cells in the CNS lesions of EAE mice are likely to be the CD45+ infiltrating immune cells such as CD4+ or F4/80+ cells and the CNS resident CD11b+ microglia and GFAP+ astrocytes, but not NeuN+ neurons. Our data suggest cytokine IL-16 is closely involved in EAE pathology as evidenced by its increased expression in the glial and infiltrating immune cells, which impacts the recruitment and activation of CD4+ immune cells in the neuroinflammation.

scholarly journals In vivo Direct Conversion of Astrocytes to Neurons Maybe a Potential Alternative Strategy for Neurodegenerative Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Youcui Wang ◽  
Xiaoqin Zhang ◽  
Fenghua Chen ◽  
Ning Song ◽  
Junxia Xie
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Degeneration ◽  
Direct Conversion ◽  
Cns Injury ◽  
Direct Reprogramming ◽  
The Central Nervous System ◽  
Potential Alternative ◽  
Neuroregenerative Medicine

Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.

scholarly journals Adipokines as Immune Cell Modulators in Multiple Sclerosis

2021 ◽  
Vol 22 (19) ◽  
pp. 10845
Author(s):  
Merel Rijnsburger ◽  
Niek Djuric ◽  
Inge A. Mulder ◽  
Helga E. de Vries
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Immune Cell ◽  
Demyelinating Disease ◽  
Therapeutic Potential ◽  
Inflammatory Factors ◽  
Low Grade ◽  
The Central Nervous System ◽  
Genetic And Environmental Factors

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

Retinal microglia polarization in diabetic retinopathy

2021 ◽  
Vol 38 ◽  
Author(s):  
Xin Li ◽  
Zi-Wei Yu ◽  
Hui-Yao Li ◽  
Yue Yuan ◽  
Xin-Yuan Gao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Diabetic Retinopathy ◽  
Cytokine Production ◽  
Immune Cell ◽  
Microvascular Disease ◽  
Retinal Diseases ◽  
Microglia Polarization ◽  
Retinal Microglia ◽  
The Central Nervous System ◽  
Retinal Neurodegeneration

Abstract Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.

scholarly journals Neurological and mental health consequences of COVID-19: potential implications for well-being and labor force

2021 ◽  
Author(s):  
I B Meier ◽  
C Vieira Ligo Teixeira ◽  
I Tarnanas ◽  
F Mirza ◽  
L Rajendran
Keyword(s):  
Mental Health ◽  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Impairment ◽  
Immune Cell ◽  
Previous History ◽  
Well Being ◽  
Acute Disseminated Encephalomyelitis ◽  
The Central Nervous System ◽  
Neurological Protection

Abstract Recent case studies show that the SARS-CoV-2 infectious disease, COVID-19, is associated with accelerated decline of mental health, in particular, cognition in elderly individuals, but also with neurological and neuropsychiatric illness in young people. Recent studies also show a bidirectional link between COVID-19 and mental health in that people with previous history of psychiatric illness have a higher risk for contracting COVID-19 and that COVID-19 patients display a variety of psychiatric illnesses. Risk factors and the response of the central nervous system to the virus show large overlaps with pathophysiological processes associated with Alzheimer’s disease, delirium, post-operative cognitive dysfunction and acute disseminated encephalomyelitis, all characterized by cognitive impairment. These similarities lead to the hypothesis that the neurological symptoms could arise from neuroinflammation and immune cell dysfunction both in the periphery as well as in the central nervous system and the assumption that long-term consequences of COVID-19 may lead to cognitive impairment in the well-being of the patient and thus in today’s workforce, resulting in large loss of productivity. Therefore, particular attention should be paid to neurological protection during treatment and recovery of COVID-19, while cognitive consequences may require monitoring.

scholarly journals Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations—A Short Overview

2021 ◽  
Vol 22 (11) ◽  
pp. 6141
Author(s):  
Teodora Larisa Timis ◽  
Ioan Alexandru Florian ◽  
Sergiu Susman ◽  
Ioan Stefan Florian
Keyword(s):  
Immune Cells ◽  
Arteriovenous Malformations ◽  
Intracranial Aneurysms ◽  
Immune Cell ◽  
Vascular Malformations ◽  
Cerebral Injury ◽  
Future Research ◽  
Mortality And Morbidity ◽  
The Central Nervous System ◽  
The Brain

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.

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