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 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.

scholarly journals Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 957
Author(s):  
Brad T. Casali ◽  
Erin G. Reed-Geaghan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cells ◽  
Expression Patterns ◽  
Brain Parenchyma ◽  
Primary Role ◽  
And Function ◽  
Inflammatory Milieu ◽  
The Brain ◽  
Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

scholarly journals Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Austin Ferro ◽  
Yohan S. S. Auguste ◽  
Lucas Cheadle
Keyword(s):  
Brain Development ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Neural Activity ◽  
Signaling Molecules ◽  
Evolutionary Strategy ◽  
Inflammatory Signaling ◽  
Peripheral Tissues ◽  
And Function ◽  
The Brain

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.

scholarly journals Novel Insight Into the Development and Function of Hypopharyngeal Glands in Honey Bees

2021 ◽  
Vol 11 ◽  
Author(s):  
Saboor Ahmad ◽  
Shahmshad Ahmed Khan ◽  
Khalid Ali Khan ◽  
Jianke Li
Keyword(s):  
Honey Bees ◽  
Future Research ◽  
Factors Affecting ◽  
Hypopharyngeal Glands ◽  
And Function ◽  
First Time ◽  
The Brain ◽  
Insight Into ◽  
Made In

Hypopharyngeal glands (HGs) are the most important organ of hymenopterans which play critical roles for the insect physiology. In honey bees, HGs are paired structures located bilaterally in the head, in front of the brain between compound eyes. Each gland is composed of thousands of secretory units connecting to secretory duct in worker bees. To better understand the recent progress made in understanding the structure and function of these glands, we here review the ontogeny of HGs, and the factors affecting the morphology, physiology, and molecular basis of the functionality of the glands. We also review the morphogenesis of HGs in the pupal and adult stages, and the secretory role of the glands across the ages for the first time. Furthermore, recent transcriptome, proteome, and phosphoproteome analyses have elucidated the potential mechanisms driving the HGs development and functionality. This adds a comprehensive novel knowledge of the development and physiology of HGs in honey bees over time, which may be helpful for future research investigations.

The Gut Microbiome as a Regulator of the Neuroimmune Landscape

2022 ◽  
Vol 40 (1) ◽  
Author(s):  
Lewis W. Yu ◽  
Gulistan Agirman ◽  
Elaine Y. Hsiao
Keyword(s):  
Gut Microbiome ◽  
Neurological Disorders ◽  
Annual Review ◽  
Publication Date ◽  
Immune Mediated ◽  
Health And Disease ◽  
And Behavior ◽  
Bidirectional Interactions ◽  
The Brain ◽  
Microbial Effects

The gut microbiome influences many host physiologies, spanning gastrointestinal function, metabolism, immune homeostasis, neuroactivity, and behavior. Many microbial effects on the host are orchestrated by bidirectional interactions between the microbiome and immune system. Imbalances in this dialogue can lead to immune dysfunction and immune-mediated conditions in distal organs including the brain. Dysbiosis of the gut microbiome and dysregulated neuroimmune responses are common comorbidities of neurodevelopmental, neuropsychiatric, and neurological disorders, highlighting the importance of the gut microbiome–neuroimmune axis as a regulator of central nervous system homeostasis. In this review, we discuss recent evidence supporting a role for the gut microbiome in regulating the neuroimmune landscape in health and disease. Expected final online publication date for the Annual Review of Immunology, Volume 40 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Microbiota-immune interactions: from gut to brain

2020 ◽  
Vol 7 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Eloisa Salvo-Romero ◽  
Patricia Stokes ◽  
Mélanie G. Gareau
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Gut Microbiota ◽  
Brain Development ◽  
Immune Cells ◽  
Autism Spectrum ◽  
Immune System Development ◽  
And Function ◽  
The Brain

The vast diversity of bacteria that inhabit the gastrointestinal tract strongly influence host physiology, not only nutrient metabolism but also immune system development and function. The complexity of the microbiota is matched by the complexity of the host immune system, where they have coevolved to maintain homeostasis ensuring the mutualistic host-microbial relationship. Numerous studies in recent years investigating the gut-brain axis have demonstrated an important role for the gut microbiota in modulating brain development and function, with the immune system serving as an important coordinator of these interactions. Gut bacteria can modulate not only gut-resident immune cells but also brain-resident immune cells. Activation of the immune system in the gut and in the brain are implicated in responses to neuroinflammation, brain injury, as well as changes in neurogenesis and plasticity. Impairments in this bidirectional communication are implicated in the etiopathogenesis of psychiatric and neurodevelopmental diseases and disorders, including autism spectrum disorders, or comorbidities associated with Gastrointestinal diseases, including inflammatory bowel diseases, where dysbiosis is commonly seen. Consequently, probiotics, or beneficial microbes, are being recognized as promising therapeutic targets to modulate behavior and brain development by modulating the gut microbiota. Here we review the role of microbiota-immune interactions in the gut and the brain during homeostasis and disease and their impact on gut-brain communication, brain function, and behavior as well as the use of probiotics in central nervous system alterations. Statement of novelty: The microbiota-gut-brain axis is increasingly recognized as an important physiological pathway for maintaining health and impacting the brain and central nervous system. Increasing evidence suggests that the immune system is crucial for gut-brain signaling. In this review, we highlight the critical studies in the literature that identify the key immune pathways involved.

Synchronizing Our Clocks as We Age: The Influence of the Brain-Gut-Immune Axis on the Sleep-Wake Cycle Across the Lifespan

SLEEP ◽  
2021 ◽  
Author(s):  
Marissa Sgro ◽  
Zoe N Kodila ◽  
Rhys D Brady ◽  
Amy C Reichelt ◽  
Richelle Mychaisuk ◽  
...  
Keyword(s):  
Complex System ◽  
Immune System ◽  
Gut Microbiome ◽  
Neurological Development ◽  
Bidirectional Relationship ◽  
Integral Role ◽  
Vital Component ◽  
And Function ◽  
Communication Pathway ◽  
The Brain

Abstract The microbes that colonize the small and large intestines, known as the gut microbiome, play an integral role in optimal brain development and function. The gut microbiome is a vital component of the bi-directional communication pathway between the brain, immune system, and gut, also known as the brain-gut-immune axis. To date there has been minimal investigation into the implications of improper development of the gut microbiome and the brain-gut-immune axis on the sleep-wake cycle, particularly during sensitive periods of physical and neurological development, such as childhood, adolescence, and senescence. Therefore, this review will explore the current literature surrounding the overlapping developmental periods of the gut microbiome, brain, and immune system from birth through to senescence, while highlighting how the brain-gut-immune axis affects maturation and organisation of the sleep-wake cycle. We also examine how dysfunction to either the microbiome or the sleep-wake cycle negatively affects the bidirectional relationship between the brain and gut, and subsequently the overall health and functionality of this complex system. Additionally, this review integrates therapeutic studies to demonstrate when dietary manipulations, such as supplementation with probiotics and prebiotics, can modulate the gut microbiome to enhance health of the brain-gut-immune axis and optimize our sleep-wake cycle.

The Gut Microbiome in Hypertension

2021 ◽  
Vol 128 (7) ◽  
pp. 934-950
Author(s):  
Ellen G. Avery ◽  
Hendrik Bartolomaeus ◽  
Andras Maifeld ◽  
Lajos Marko ◽  
Helge Wiig ◽  
...  
Keyword(s):  
Immune Cells ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
The Body ◽  
Model Systems ◽  
Future Research ◽  
Hypertensive Disease ◽  
Preclinical Research ◽  
Ongoing Research ◽  
Diverse Range

The pathogenesis of hypertension is known to involve a diverse range of contributing factors including genetic, environmental, hormonal, hemodynamic and inflammatory forces, to name a few. There is mounting evidence to suggest that the gut microbiome plays an important role in the development and pathogenesis of hypertension. The gastrointestinal tract, which houses the largest compartment of immune cells in the body, represents the intersection of the environment and the host. Accordingly, lifestyle factors shape and are modulated by the microbiome, modifying the risk for hypertensive disease. One well-studied example is the consumption of dietary fibers, which leads to the production of short-chain fatty acids and can contribute to the expansion of anti-inflammatory immune cells, consequently protecting against the progression of hypertension. Dietary interventions such as fasting have also been shown to impact hypertension via the microbiome. Studying the microbiome in hypertensive disease presents a variety of unique challenges to the use of traditional model systems. Integrating microbiome considerations into preclinical research is crucial, and novel strategies to account for reciprocal host-microbiome interactions, such as the wildling mouse model, may provide new opportunities for translation. The intricacies of the role of the microbiome in hypertensive disease is a matter of ongoing research, and there are several technical considerations which should be accounted for moving forward. In this review we provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure. Additionally, we provide recommendations for ongoing and future research, such that important insights from the microbiome field at large can be readily integrated in the context of hypertension.

Kisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms

2012 ◽  
Vol 92 (3) ◽  
pp. 1235-1316 ◽  
Author(s):  
Leonor Pinilla ◽  
Enrique Aguilar ◽  
Carlos Dieguez ◽  
Robert P. Millar ◽  
Manuel Tena-Sempere
Keyword(s):  
Biological Effects ◽  
Reproductive Function ◽  
Future Research ◽  
Gonadotropin Secretion ◽  
Integral Control ◽  
Molecular Features ◽  
Hypothalamic Nuclei ◽  
Key Aspects ◽  
And Function ◽  
The Brain

Procreation is essential for survival of species. Not surprisingly, complex neuronal networks have evolved to mediate the diverse internal and external environmental inputs that regulate reproduction in vertebrates. Ultimately, these regulatory factors impinge, directly or indirectly, on a final common pathway, the neurons producing the gonadotropin-releasing hormone (GnRH), which stimulates pituitary gonadotropin secretion and thereby gonadal function. Compelling evidence, accumulated in the last few years, has revealed that kisspeptins, a family of neuropeptides encoded by the Kiss1 gene and produced mainly by neuronal clusters at discrete hypothalamic nuclei, are pivotal upstream regulators of GnRH neurons. As such, kisspeptins have emerged as important gatekeepers of key aspects of reproductive maturation and function, from sexual differentiation of the brain and puberty onset to adult regulation of gonadotropin secretion and the metabolic control of fertility. This review aims to provide a comprehensive account of the state-of-the-art in the field of kisspeptin physiology by covering in-depth the consensus knowledge on the major molecular features, biological effects, and mechanisms of action of kisspeptins in mammals and, to a lesser extent, in nonmammalian vertebrates. This review will also address unsolved and contentious issues to set the scene for future research challenges in the area. By doing so, we aim to endow the reader with a critical and updated view of the physiological roles and potential translational relevance of kisspeptins in the integral control of reproductive function.

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.

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