Neuropathogenesis: rogue glia cause mayhem in the brain

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Joseph Antony
Keyword(s):  
Glial Cells ◽  
Immune Cells ◽  
Neurological Disorders ◽  
White Matter Injury ◽  
Periventricular White Matter ◽  
Brain Functions ◽  
Aids Dementia ◽  
Injured Tissue ◽  
Injured Brain ◽  
The Brain

AbstractGlia, including astrocytes, microglia and oligodendrocytes, are important components that maintain the architecture of the brain and in many ways contribute to the proper functioning of neurons. Glial cells vastly outnumber neurons in the brain and independently control several crucial brain functions. Impaired glial cells are the cause of several diseases, and pharmacological targeting to repair damaged glia will enable functional recovery in patients suffering from devastating neurological disorders. The interaction between glial cells and some patrolling immune cells in the brain comprise the brain-specific immune system that protects the brain from extraneous agents and repairs injured tissue. While this system can cope with minor insults and infections, when faced with significant challenges such as AIDS dementia, multiple sclerosis, Huntington’s disease, Parkinson’s disease, etc., an effective and balanced immune response that facilitates repair and protection is found wanting. Several debilitating neurological disorders are often associated with dysfunctional glial cells that have limited ability to repair the injured brain and even promote brain damage. In this discussion, specific signaling pathways in glia that are affected in AIDS dementia and periventricular white matter injury will be highlighted.

scholarly journals Current Paradigms to Explore the Gut Microbiota Linkage to Neurological Disorders

EMJ Neurology ◽  
2020 ◽  
pp. 68-79
Author(s):  
Varruchi Sharma ◽  
Atul Sankhyan ◽  
Anshika Varshney ◽  
Renuka Choudhary ◽  
Anil K. Sharma
Keyword(s):  
Gut Microbiota ◽  
Neurological Disorders ◽  
Brain Function ◽  
Intervention Strategy ◽  
Neurological Complications ◽  
Communication Link ◽  
Brain Functions ◽  
Current Review ◽  
The Impact ◽  
The Brain

It has been suggested that an intricate communication link exists between the gut microbiota and the brain and its ability to modulate behaviour of an individual governing homeostasis. Metabolic activity of the microbiota is considered to be relatively constant in healthy individuals, despite differences in the composition of microbiota. The metabolites produced by gut microbiota and their homeostatic balance is often perturbed as a result of neurological complications. Therefore, it is of paramount importance to explore the link between gut microbiota and brain function and behaviour through neural, endocrine, and immune pathways. This current review focusses on the impact of altered gut microbiota on brain functions and how microbiome modulation by use of probiotics, prebiotics, and synbiotics might prove beneficial in the prevention and/or treatment of neurological disorders. It is important to carefully understand the complex mechanisms underlying the gut–brain axis so as to use the gut microbiota as a therapeutic intervention strategy for neurological disorders.

Dissecting the regional diversity of glial cells by applying -omic technologies

e-Neuroforum ◽  
2015 ◽  
Vol 21 (3) ◽  
Author(s):  
Daniela C. Dieterich ◽  
Moritz J. Rossner
Keyword(s):  
Glial Cells ◽  
Brain Function ◽  
Recent Progress ◽  
Higher Order ◽  
Cell Populations ◽  
Cellular Activity ◽  
Regional Diversity ◽  
Brain Functions ◽  
Exploratory Approach ◽  
The Brain

AbstractNeuronal as well as glial cells contribute to higher order brain functions. Many observations show that neurons and glial cells are not only physically highly intermingled but are physiologically tightly connected and mutually depend at various levels on each other. Moreover, macroglia classes like astrocytes, NG2 cells and oligodendrocytes are not at all homogenous cell populations but do possess a markedly heterogeneity in various aspects similar to neurons. The diversity of differences in morphology, functionality and, cellular activity has been acknowledged recently and will be integrated into a concept of brain function that pictures a neural rather than a puristical neuronal world. With the recent progress in “omic” technologies, an unbiased and exploratory approach toward an enhanced understanding of glial heterogeneity has become possible. Here, we provide an overview on current technical transcriptomic and proteomic approaches used to dissect glial heterogeneity of the brain.

scholarly journals Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain

2018 ◽  
Author(s):  
Timothy R. Hammond ◽  
Connor Dufort ◽  
Lasse Dissing-Olesen ◽  
Stefanie Giera ◽  
Adam Young ◽  
...  
Keyword(s):  
Brain Injury ◽  
Immune Cells ◽  
Expression Patterns ◽  
Rna Expression ◽  
Complex Cell ◽  
Injured Brain ◽  
Single Cell Rna Sequencing ◽  
Health And Disease ◽  
State Changes ◽  
The Brain

Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. In this study, we analyzed the RNA expression patterns of more than 76,000 individual microglia during development, old age and after brain injury. Analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states - including chemokine-enriched inflammatory microglia - persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human MS lesions. These unique microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.

scholarly journals Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

2019 ◽  
Vol 20 (4) ◽  
pp. 996 ◽  
Author(s):  
Eiji Shigetomi ◽  
Kozo Saito ◽  
Fumikazu Sano ◽  
Schuichi Koizumi
Keyword(s):  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Brain Disease ◽  
Reactive Astrocytes ◽  
Brain Functions ◽  
Progression Of Disease ◽  
Brain Insults ◽  
The Brain

Astrocytes are abundant cells in the brain that regulate multiple aspects of neural tissue homeostasis by providing structural and metabolic support to neurons, maintaining synaptic environments and regulating blood flow. Recent evidence indicates that astrocytes also actively participate in brain functions and play a key role in brain disease by responding to neuronal activities and brain insults. Astrocytes become reactive in response to injury and inflammation, which is typically described as hypertrophy with increased expression of glial fibrillary acidic protein (GFAP). Reactive astrocytes are frequently found in many neurological disorders and are a hallmark of brain disease. Furthermore, reactive astrocytes may drive the initiation and progression of disease processes. Recent improvements in the methods to visualize the activity of reactive astrocytes in situ and in vivo have helped elucidate their functions. Ca2+ signals in reactive astrocytes are closely related to multiple aspects of disease and can be a good indicator of disease severity/state. In this review, we summarize recent findings concerning reactive astrocyte Ca2+ signals. We discuss the molecular mechanisms underlying aberrant Ca2+ signals in reactive astrocytes and the functional significance of aberrant Ca2+ signals in neurological disorders.

scholarly journals Microbiome–microglia connections via the gut–brain axis

2018 ◽  
Vol 216 (1) ◽  
pp. 41-59 ◽  
Author(s):  
Reem Abdel-Haq ◽  
Johannes C.M. Schlachetzki ◽  
Christopher K. Glass ◽  
Sarkis K. Mazmanian
Keyword(s):  
Immune Cells ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Microbial Community Composition ◽  
Future Research ◽  
Gi Tract ◽  
Synaptic Remodeling ◽  
And Function ◽  
The Brain ◽  
Microglial Development

Microglia, the resident immune cells in the brain, are essential for modulating neurogenesis, influencing synaptic remodeling, and regulating neuroinflammation by surveying the brain microenvironment. Microglial dysfunction has been implicated in the onset and progression of several neurodevelopmental and neurodegenerative diseases; however, the multitude of factors and signals influencing microglial activity have not been fully elucidated. Microglia not only respond to local signals within the brain but also receive input from the periphery, including the gastrointestinal (GI) tract. Recent preclinical findings suggest that the gut microbiome plays a pivotal role in regulating microglial maturation and function, and altered microbial community composition has been reported in neurological disorders with known microglial involvement in humans. Collectively, these findings suggest that bidirectional crosstalk between the gut and the brain may influence disease pathogenesis. Herein, we discuss recent studies showing a role for the gut microbiome in modulating microglial development and function in homeostatic and disease conditions and highlight possible future research to develop novel microbial treatments for disorders of the brain.

scholarly journals Glial Cells Promote Myelin Formation and Elimination

2021 ◽  
Vol 9 ◽  
Author(s):  
Alexandria N. Hughes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glial Cells ◽  
Cell Types ◽  
Brain Functions ◽  
Myelin Sheaths ◽  
Local Signaling ◽  
The Brain ◽  
Vertebrate Central Nervous System

Building a functional nervous system requires the coordinated actions of many glial cells. In the vertebrate central nervous system (CNS), oligodendrocytes myelinate neuronal axons to increase conduction velocity and provide trophic support. Myelination can be modified by local signaling at the axon-myelin interface, potentially adapting sheaths to support the metabolic needs and physiology of individual neurons. However, neurons and oligodendrocytes are not wholly responsible for crafting the myelination patterns seen in vivo. Other cell types of the CNS, including microglia and astrocytes, modify myelination. In this review, I cover the contributions of non-neuronal, non-oligodendroglial cells to the formation, maintenance, and pruning of myelin sheaths. I address ways that these cell types interact with the oligodendrocyte lineage throughout development to modify myelination. Additionally, I discuss mechanisms by which these cells may indirectly tune myelination by regulating neuronal activity. Understanding how glial-glial interactions regulate myelination is essential for understanding how the brain functions as a whole and for developing strategies to repair myelin in disease.

The gut-brain axis: microglia in the spotlight

Neuroforum ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 205-212 ◽  
Author(s):  
Charlotte Mezö ◽  
Omar Mossad ◽  
Daniel Erny ◽  
Thomas Blank
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Brain Functions ◽  
Microbiome Research ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Summary Microbiome research has grown significantly in the last decade, highlighting manifold implications of the microbiota to the host’s health. The gut microbiota is connected to the brain through several avenues that allow their interaction. Thus, recent studies have attemtpted to characterize these connections and enhance our understanding of the so called ‘gut-brain-axis’. Microglia, the central nervous system resident macrophages, are crucial for the proper development and maintenance of brain functions. As immune cells, they are in the spotlight for relaying signals between the microbiota and cells of the brain. In this review, we contemplate on interactions between the gut microbiota and microglia, and their influence on brain functions in health and disease.

scholarly journals Functional imaging in neurosciences

2015 ◽  
Vol 02 (03) ◽  
pp. 240-245
Author(s):  
Sriganesh Kamath ◽  
G Umamaheswara Rao
Keyword(s):  
Magnetic Resonance Imaging ◽  
Functional Imaging ◽  
Neurological Disorders ◽  
Imaging Techniques ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Brain Functions ◽  
Health And Disease ◽  
Neurological Conditions ◽  
The Brain

AbstractRecent advances in functional imaging of the brain have enabled a better understanding of the brain functions in health and disease. Amongst various functional imaging techniques, functional magnetic resonance imaging (fMRI) has been more rigorously employed in both clinical practice and in the research arena. This review will discuss the principles and techniques of fMRI, its role in understanding the pathophysiology of brain injury and finally, its clinical application in diagnosing neurological conditions and prognostication of outcome in patients with neurological disorders.

scholarly journals Cellular Senescence in Brain Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Ewa Sikora ◽  
Anna Bielak-Zmijewska ◽  
Magdalena Dudkowska ◽  
Adam Krzystyniak ◽  
Grazyna Mosieniak ◽  
...  
Keyword(s):  
Glial Cells ◽  
Cellular Senescence ◽  
Dendritic Spines ◽  
Neuronal Plasticity ◽  
Brain Aging ◽  
Aging Brain ◽  
Peripheral Tissues ◽  
Brain Functions ◽  
The Brain

Aging of the brain can manifest itself as a memory and cognitive decline, which has been shown to frequently coincide with changes in the structural plasticity of dendritic spines. Decreased number and maturity of spines in aged animals and humans, together with changes in synaptic transmission, may reflect aberrant neuronal plasticity directly associated with impaired brain functions. In extreme, a neurodegenerative disease, which completely devastates the basic functions of the brain, may develop. While cellular senescence in peripheral tissues has recently been linked to aging and a number of aging-related disorders, its involvement in brain aging is just beginning to be explored. However, accumulated evidence suggests that cell senescence may play a role in the aging of the brain, as it has been documented in other organs. Senescent cells stop dividing and shift their activity to strengthen the secretory function, which leads to the acquisition of the so called senescence-associated secretory phenotype (SASP). Senescent cells have also other characteristics, such as altered morphology and proteostasis, decreased propensity to undergo apoptosis, autophagy impairment, accumulation of lipid droplets, increased activity of senescence-associated-β-galactosidase (SA-β-gal), and epigenetic alterations, including DNA methylation, chromatin remodeling, and histone post-translational modifications that, in consequence, result in altered gene expression. Proliferation-competent glial cells can undergo senescence both in vitro and in vivo, and they likely participate in neuroinflammation, which is characteristic for the aging brain. However, apart from proliferation-competent glial cells, the brain consists of post-mitotic neurons. Interestingly, it has emerged recently, that non-proliferating neuronal cells present in the brain or cultivated in vitro can also have some hallmarks, including SASP, typical for senescent cells that ceased to divide. It has been documented that so called senolytics, which by definition, eliminate senescent cells, can improve cognitive ability in mice models. In this review, we ask questions about the role of senescent brain cells in brain plasticity and cognitive functions impairments and how senolytics can improve them. We will discuss whether neuronal plasticity, defined as morphological and functional changes at the level of neurons and dendritic spines, can be the hallmark of neuronal senescence susceptible to the effects of senolytics.

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