scholarly journals Drosophila as a Model for Microbiota Studies of Neurodegeneration

2021 ◽  
pp. 1-12
Author(s):  
Fukiko Kitani-Morii ◽  
Robert P. Friedland ◽  
Hideki Yoshida ◽  
Toshiki Mizuno
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Fruit Fly ◽  
Endocrine Regulation ◽  
Nutrient Metabolism ◽  
Host Health ◽  
And Behavior ◽  
The Brain ◽  
Lateral Sclerosis

Accumulating evidence show that the gut microbiota is deeply involved not only in host nutrient metabolism but also in immune function, endocrine regulation, and chronic disease. In neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis, the gut-brain axis, the bidirectional interaction between the brain and the gut, provides new route of pathological spread and potential therapeutic targets. Although studies of gut microbiota have been conducted mainly in mice, mammalian gut microbiota is highly diverse, complex, and sensitive to environmental changes. Drosophila melanogaster, a fruit fly, has many advantages as a laboratory animal: short life cycle, numerous and genetically homogenous offspring, less ethical concerns, availability of many genetic models, and low maintenance costs. Drosophila has a simpler gut microbiota than mammals and can be made to remain sterile or to have standardized gut microbiota by simple established methods. Research on the microbiota of Drosophila has revealed new molecules that regulate the brain-gut axis, and it has been shown that dysbiosis of the fly microbiota worsens lifespan, motor function, and neurodegeneration in AD and PD models. The results shown in fly studies represents a fundamental part of the immune and proteomic process involving gut-microbiota interactions that are highly conserved. Even though the fly’s gut microbiota are not simple mimics of humans, flies are a valuable system to learn the molecular mechanisms of how the gut microbiota affect host health and behavior.

scholarly journals Cerebral sterile inflammation in neurodegenerative diseases

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Kento Otani ◽  
Takashi Shichita
Keyword(s):  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Sterile Inflammation ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Abnormal Accumulation ◽  
The Brain ◽  
Lateral Sclerosis

AbstractTherapeutic strategies for regulating neuroinflammation are expected in the development of novel therapeutic agents to prevent the progression of central nervous system (CNS) pathologies. An understanding of the detailed molecular and cellular mechanisms of neuroinflammation in each CNS disease is necessary for the development of therapeutics. Since the brain is a sterile organ, neuroinflammation in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) is triggered by cerebral cellular damage or the abnormal accumulation of inflammatogenic molecules in CNS tissue through the activation of innate and acquired immunity. Inflammation and CNS pathologies worsen each other through various cellular and molecular mechanisms, such as oxidative stress or the accumulation of inflammatogenic molecules induced in the damaged CNS tissue. In this review, we summarize the recent evidence regarding sterile immune responses in neurodegenerative diseases.

scholarly journals Gut–Brain Axis and Neurodegeneration: State-of-the-Art of Meta-Omics Sciences for Microbiota Characterization

2020 ◽  
Vol 21 (11) ◽  
pp. 4045 ◽  
Author(s):  
Bruno Tilocca ◽  
Luisa Pieroni ◽  
Alessio Soggiu ◽  
Domenico Britti ◽  
Luigi Bonizzi ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
State Of The Art ◽  
Integrated Approach ◽  
Microbial Genomes ◽  
Physiological Processes ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Recent advances in the field of meta-omics sciences and related bioinformatics tools have allowed a comprehensive investigation of human-associated microbiota and its contribution to achieving and maintaining the homeostatic balance. Bioactive compounds from the microbial community harboring the human gut are involved in a finely tuned network of interconnections with the host, orchestrating a wide variety of physiological processes. These includes the bi-directional crosstalk between the central nervous system, the enteric nervous system, and the gastrointestinal tract (i.e., gut–brain axis). The increasing accumulation of evidence suggest a pivotal role of the composition and activity of the gut microbiota in neurodegeneration. In the present review we aim to provide an overview of the state-of-the-art of meta-omics sciences including metagenomics for the study of microbial genomes and taxa strains, metatranscriptomics for gene expression, metaproteomics and metabolomics to identify and/or quantify microbial proteins and metabolites, respectively. The potential and limitations of each discipline were highlighted, as well as the advantages of an integrated approach (multi-omics) to predict microbial functions and molecular mechanisms related to human diseases. Particular emphasis is given to the latest results obtained with these approaches in an attempt to elucidate the link between the gut microbiota and the most common neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).

scholarly journals Gut microbiota, the pharmabiotics they produce and host health

2014 ◽  
Vol 73 (4) ◽  
pp. 477-489 ◽  
Author(s):  
Elaine Patterson ◽  
John F. Cryan ◽  
Gerald F. Fitzgerald ◽  
R. Paul Ross ◽  
Timothy G. Dinan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Brain Function ◽  
Innate Immune ◽  
Aminobutyric Acid ◽  
Intestinal Lumen ◽  
Bioactive Metabolites ◽  
Bioactive Lipids ◽  
Disease States ◽  
Host Health ◽  
The Brain

A healthy gut microbiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or ‘pharmabiotics’. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gut microbiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain–gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gut microbiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.

scholarly journals A connectome is not enough – what is still needed to understand the brain of Drosophila?

2021 ◽  
Vol 224 (21) ◽  
Author(s):  
Louis K. Scheffer ◽  
Ian A. Meinertzhagen
Keyword(s):  
Electron Microscopy ◽  
Nervous System ◽  
Fruit Fly ◽  
Synaptic Connections ◽  
Model Species ◽  
Electron Microscopy Level ◽  
Near Term ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain

ABSTRACT Understanding the structure and operation of any nervous system has been a subject of research for well over a century. A near-term opportunity in this quest is to understand the brain of a model species, the fruit fly Drosophila melanogaster. This is an enticing target given its relatively small size (roughly 200,000 neurons), coupled with the behavioral richness that this brain supports, and the wide variety of techniques now available to study both brain and behavior. It is clear that within a few years we will possess a connectome for D. melanogaster: an electron-microscopy-level description of all neurons and their chemical synaptic connections. Given what we will soon have, what we already know and the research that is currently underway, what more do we need to know to enable us to understand the fly's brain? Here, we itemize the data we will need to obtain, collate and organize in order to build an integrated model of the brain of D. melanogaster.

Gut Microbiota and Alzheimer’s Disease: Experimental Evidence and Clinical Reality

2021 ◽  
Vol 18 ◽  
Author(s):  
Sarama Saha ◽  
Sukhpal Singh ◽  
Suvarna Prasad ◽  
Amit Mittal ◽  
Anil Kumar Sharma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Bacterial Flora ◽  
Experimental Studies ◽  
The Elderly ◽  
The Impact ◽  
The Brain

: Alzheimer’s disease (AD) is characterized by progressive death of neuronal cells in the regions of the brain concerned with memory and cognition, and is the major cause of dementia in the elderly population. Various molecular mechanisms, metabolic risk factors and environmental triggers contributing to the genesis and progression of AD are under intense investigations. The present review has dealt with the impact of a highly discussed topic of gut microbiota affecting the neurodegeneration in the AD brain. A detailed description of the composition of gut bacterial flora and its interaction with the host has been presented, followed by an analysis of key concepts of bi- directional communication between gut microbiota and the brain. The substantial experimental evidence of gut microbiota affecting the neurodegenerative process in experimental AD models has been described next in this review, and finally, the limitations of such experimental studies vis-a- vis the actual disease and the paucity of clinical data on this topic have also been mentioned.

Neural and Molecular Mechanisms of Biological Embedding of Social Interactions

2021 ◽  
Vol 44 (1) ◽  
pp. 109-128
Author(s):  
Ian M. Traniello ◽  
Gene E. Robinson
Keyword(s):  
Social Interactions ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Special Focus ◽  
Complex Environments ◽  
Social Stimuli ◽  
Multiple Levels ◽  
Social Decision Making ◽  
The Brain ◽  
Subsequent Modification

Animals operate in complex environments, and salient social information is encoded in the nervous system and then processed to initiate adaptive behavior. This encoding involves biological embedding, the process by which social experience affects the brain to influence future behavior. Biological embedding is an important conceptual framework for understanding social decision-making in the brain, as it encompasses multiple levels of organization that regulate how information is encoded and used to modify behavior. The framework we emphasize here is that social stimuli provoke short-term changes in neural activity that lead to changes in gene expression on longer timescales. This process, simplified—neurons are for today and genes are for tomorrow—enables the assessment of the valence of a social interaction, an appropriate and rapid response, and subsequent modification of neural circuitry to change future behavioral inclinations in anticipation of environmental changes. We review recent research on the neural and molecular basis of biological embedding in the context of social interactions, with a special focus on the honeybee.

scholarly journals The Toll Route to Structural Brain Plasticity

2021 ◽  
Vol 12 ◽  
Author(s):  
Guiyi Li ◽  
Alicia Hidalgo
Keyword(s):  
Human Brain ◽  
Molecular Mechanisms ◽  
Brain Plasticity ◽  
Model Organism ◽  
Structural Plasticity ◽  
Fruit Fly ◽  
Adult Brain ◽  
And Behavior ◽  
Structural Brain

The human brain can change throughout life as we learn, adapt and age. A balance between structural brain plasticity and homeostasis characterizes the healthy brain, and the breakdown of this balance accompanies brain tumors, psychiatric disorders, and neurodegenerative diseases. However, the link between circuit modifications, brain function, and behavior remains unclear. Importantly, the underlying molecular mechanisms are starting to be uncovered. The fruit-fly Drosophila is a very powerful model organism to discover molecular mechanisms and test them in vivo. There is abundant evidence that the Drosophila brain is plastic, and here we travel from the pioneering discoveries to recent findings and progress on molecular mechanisms. We pause on the recent discovery that, in the Drosophila central nervous system, Toll receptors—which bind neurotrophin ligands—regulate structural plasticity during development and in the adult brain. Through their topographic distribution across distinct brain modules and their ability to switch between alternative signaling outcomes, Tolls can enable the brain to translate experience into structural change. Intriguing similarities between Toll and mammalian Toll-like receptor function could reveal a further involvement in structural plasticity, degeneration, and disease in the human brain.

scholarly journals Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1765 ◽  
Author(s):  
Vo Giau ◽  
Si Wu ◽  
Angelo Jamerlan ◽  
Seong An ◽  
SangYun Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Brain And Behavior ◽  
Underlying Mechanisms ◽  
And Behavior ◽  
The Impact ◽  
The Brain

The bidirectional communication between the central nervous system (CNS) and the gut microbiota plays a pivotal role in human health. Increasing numbers of studies suggest that the gut microbiota can influence the brain and behavior of patients. Various metabolites secreted by the gut microbiota can affect the cognitive ability of patients diagnosed with neurodegenerative diseases. Nearly one in every ten Korean senior citizens suffers from Alzheimer’s disease (AD), the most common form of dementia. This review highlights the impact of metabolites from the gut microbiota on communication pathways between the brain and gut, as well as the neuroinflammatory roles they may have in AD patients. The objectives of this review are as follows: (1) to examine the role of the intestinal microbiota in homeostatic communication between the gut microbiota and the brain, termed the microbiota–gut–brain (MGB) axis; (2) to determine the underlying mechanisms of signal dysfunction; and (3) to assess the impact of signal dysfunction induced by the microbiota on AD. This review will aid in understanding the microbiota of elderly people and the neuroinflammatory roles they may have in AD.

scholarly journals Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain

Metabolites ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 172 ◽  
Author(s):  
Jonathan R. Swann ◽  
Sonia O. Spitzer ◽  
Rochellys Diaz Heijtz
Keyword(s):  
Gut Microbiome ◽  
Developmental Stages ◽  
Bioactive Molecules ◽  
Liquid Chromatography Mass Spectrometry ◽  
Host Health ◽  
Health And Disease ◽  
And Behavior ◽  
Precursor Molecules ◽  
The Brain ◽  
Metabolomic Approach

The gut microbiome is recognized to exert a wide-ranging influence on host health and disease, including brain development and behavior. Commensal bacteria can produce bioactive molecules that enter the circulation and impact host physiology and homeostasis. However, little is known about the potential for these metabolites to cross the blood–brain barrier and enter the developing brain under normal physiological conditions. In this study, we used a liquid chromatography–mass spectrometry-based metabolomic approach to characterize the developmental profiles of microbial-derived metabolites in the forebrains of mice across three key postnatal developmental stages, co-occurring with the maturation of the gut microbiota. We demonstrate that direct metabolites of the gut microbiome (e.g., imidazole propionate) or products of the combinatorial metabolism between the microbiome and host (e.g., 3-indoxyl-sulfate, trimethylamine-N-oxide, and phenylacetylglycine) are present in the forebrains of mice as early as the neonatal period and remain into adulthood. These findings demonstrate that microbial-associated molecules can cross the BBB either in their detected form or as precursor molecules that undergo further processing in the brain. These chemical messengers are able to bind receptors known to be expressed in the brain. Alterations in the gut microbiome may therefore influence neurodevelopmental trajectories via the regulation of these microbial-associated metabolites.

Gut Hormones and Neuropeptides as Mediators of Microbiome–Brain Communication

2020 ◽  
Author(s):  
Peter Holzer ◽  
Aitak Farzi
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Trophic Factors ◽  
And Behavior ◽  
Communication Lines ◽  
Secondary Chemical ◽  
The Brain ◽  
Secondary Bile Acids

The gut microbiota interacts with the brain through multiple communication lines in which gut peptide hormones and neuropeptides play important messenger roles. These peptides are secondary chemical signals whose operation is controlled by the gut microbiota via a myriad of microbial metabolites, secondary bile acids, and structural components. We first outline a number of gut hormones (e.g., peptide YY, glucagon-like peptide, ghrelin, cholecystokinin) which communicate with the brain either via the circulation or via vagal afferent neurons. Several neuropeptides in the brain are likewise under the influence of gut microbes and mediate their impact on various aspects of brain function and behavior. These neuropeptides include neuropeptide Y, corticotropin-releasing factor, brain-derived neurotrophic factor, and several other peptides which act as neurotransmitters or trophic factors. Food intake, energy homeostasis, emotional-affective behavior, cognitive performance, stress resilience, and neurogenesis are among the processes which the gut microbiota regulates via the action of gut hormones and neuropeptides.

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