scholarly journals Gut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Gabriele Deidda ◽  
Manuele Biazzo
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Strategy ◽  
Brain Diseases ◽  
Microbial Populations ◽  
Normal Brain ◽  
Neuronal Populations ◽  
Brain Physiology ◽  
Pathological Conditions ◽  
The Brain

Brain physiological functions or pathological dysfunctions do surely depend on the activity of both neuronal and non-neuronal populations. Nevertheless, over the last decades, compelling and fast accumulating evidence showed that the brain is not alone. Indeed, the so-called “gut brain,” composed of the microbial populations living in the gut, forms a symbiotic superorganism weighing as the human brain and strongly communicating with the latter via the gut–brain axis. The gut brain does exert a control on brain (dys)functions and it will eventually become a promising valuable therapeutic target for a number of brain pathologies. In the present review, we will first describe the role of gut microbiota in normal brain physiology from neurodevelopment till adulthood, and thereafter we will discuss evidence from the literature showing how gut microbiota alterations are a signature in a number of brain pathologies ranging from neurodevelopmental to neurodegenerative disorders, and how pre/probiotic supplement interventions aimed to correct the altered dysbiosis in pathological conditions may represent a valuable future therapeutic strategy.

scholarly journals Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahmoud Salami
Keyword(s):  
Gut Microbiota ◽  
Cognitive Processing ◽  
Clinical Problem ◽  
The Body ◽  
Brain Diseases ◽  
Normal Brain ◽  
Beneficial Effects ◽  
Normal Brain Function ◽  
The Brain ◽  
Common Clinical Problem

The human gastrointestinal tract hosts trillions of microorganisms that is called “gut microbiota.” The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

scholarly journals Altered GABA Signaling in Early Life Epilepsies

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Stephen W. Briggs ◽  
Aristea S. Galanopoulou
Keyword(s):  
Brain Function ◽  
Therapeutic Potential ◽  
Physiological Role ◽  
Neuronal Morphology ◽  
Normal Brain ◽  
Pathological Conditions ◽  
Neurodevelopmental Deficits ◽  
The Brain ◽  
Normal Brain Development

The incidence of seizures is particularly high in the early ages of life. The immaturity of inhibitory systems, such as GABA, during normal brain development and its further dysregulation under pathological conditions that predispose to seizures have been speculated to play a major role in facilitating seizures. Seizures can further impair or disrupt GABAAsignaling by reshuffling the subunit composition of its receptors or causing aberrant reappearance of depolarizing or hyperpolarizing GABAAreceptor currents. Such effects may not result in epileptogenesis as frequently as they do in adults. Given the central role of GABAAsignaling in brain function and development, perturbation of its physiological role may interfere with neuronal morphology, differentiation, and connectivity, manifesting as cognitive or neurodevelopmental deficits. The current GABAergic antiepileptic drugs, while often effective for adults, are not always capable of stopping seizures and preventing their sequelae in neonates. Recent studies have explored the therapeutic potential of chloride cotransporter inhibitors, such as bumetanide, as adjunctive therapies of neonatal seizures. However, more needs to be known so as to develop therapies capable of stopping seizures while preserving the age- and sex-appropriate development of the brain.

SPONTANEOUS SIGNALLING IN SMALL CENTRAL NEURONS: MECHANISMS AND ROLES OF SPIKE-AMPLITUDE AND SPIKE-INTERVAL FLUCTUATIONS

1996 ◽  
Vol 07 (04) ◽  
pp. 369-376 ◽  
Author(s):  
PETER ÅRHEM ◽  
STAFFAN JOHANSSON
Keyword(s):  
Spontaneous Activity ◽  
Electric Fields ◽  
Hippocampal Neurons ◽  
Brain Activity ◽  
Cortical Network ◽  
Normal Brain ◽  
Brain Physiology ◽  
Random Generators ◽  
The Brain

Spontaneous brain activity is essential for normal brain function. We are studying spontaneous activity in hippocampus at several complexity levels: at the microscopic level by analyzing the role of ion channels, at the mesoscopic level by analyzing the neuronal impulse activity, and at the macroscopic level by computational studies of mean electric fields of cortical network models. We have focused on the role of a subset of hippocampal neurons in the rat — neurons of small size (diameter <10 µ m ). The analysis of spontaneous impulse trains in these neurons, both isolated and in slices, show (i) that impulses vary in amplitude, the magnitude depending on the input signal, suggesting that the amplitude variability may play a role in the information processing of the brain, and (ii) that single ion channel events can trigger neuronal impulses, suggesting that these neurons can function as cellular random generators. The possible role of random generators are investigated by simulating spontaneous activity in a cortical network model, based on a simplified description of the architecture of the CA1 area of hippocampus. The simulations show that such random generators can induce synchronous oscillations in cortical networks. These findings highlight the role of microfluctuations for the global macroactivity of the brain, and stress the importance of the study of channel kinetics for brain physiology.

scholarly journals Microbiota Gut–Brain Axis in Ischemic Stroke: A Narrative Review with a Focus about the Relationship with Inflammatory Bowel Disease

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 715
Author(s):  
Emanuele Sinagra ◽  
Gaia Pellegatta ◽  
Valentina Guarnotta ◽  
Marcello Maida ◽  
Francesca Rossi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Ischemic Stroke ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Brain Diseases ◽  
Starting Point ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Brain

The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer’s disease, and Parkinson’s disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidences concerning the role of the gut–brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut–brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke.

scholarly journals Role of Microglia Adenosine A2AReceptors in Retinal and Brain Neurodegenerative Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Ana R. Santiago ◽  
Filipa I. Baptista ◽  
Paulo F. Santos ◽  
Gonçalo Cristóvão ◽  
António F. Ambrósio ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Brain Diseases ◽  
Degenerative Diseases ◽  
Chronic Neuroinflammation ◽  
Retinal Degenerative Diseases ◽  
G Protein Coupled ◽  
The Brain

Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential therapeutic strategy. The neuromodulator adenosine emerges as a promising targeting candidate based on its ability to regulate microglial proliferation, chemotaxis, and reactivity through the activation of its G protein coupledA2Areceptor (A2AR). This is in striking agreement with the ability ofA2ARblockade to control several brain diseases. Retinal degenerative diseases have been also associated with microglia-mediated neuroinflammation, but the role ofA2ARhas been scarcely explored. This review aims to compare inflammatory features of Parkinson’s and Alzheimer’s diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential ofA2ARin these degenerative conditions.

Targeting neutrophils as a novel therapeutic strategy after stroke

2021 ◽  
pp. 0271678X2110001
Author(s):  
Chen Chen ◽  
Tingting Huang ◽  
Xiaozhu Zhai ◽  
Yezhi Ma ◽  
Lv Xie ◽  
...  
Keyword(s):  
Brain Damage ◽  
Therapeutic Strategy ◽  
Therapeutic Strategies ◽  
Ischemic Brain ◽  
Pathological Conditions ◽  
Single Cell Rna Sequencing ◽  
Full Knowledge ◽  
Neutrophil Response ◽  
The Brain

Stroke is followed by an intricate immune interaction involving the engagement of multiple immune cells, including neutrophils. As one of the first responders recruited to the brain, the crucial roles of neutrophils in the ischemic brain damage are receiving increasing attention in recent years. Notably, neutrophils are not homogenous, and yet there is still a lack of full knowledge about the extent and impact of neutrophil heterogeneity. The biological understanding of the neutrophil response to both innate and pathological conditions is rapidly evolving as single-cell-RNA sequencing uncovers overall neutrophil profiling across maturation and differentiation contexts. In this review, we scrutinize the latest research that points to the multifaceted role of neutrophils in different conditions and summarize the regulatory signals that may determine neutrophil diversity. In addition, we list several potential targets or therapeutic strategies targeting neutrophils to limit brain damage following ischemic stroke.

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

scholarly journals Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 334
Author(s):  
Huilong Luo ◽  
Xavier Declèves ◽  
Salvatore Cisternino
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Brain Diseases ◽  
Transient Receptor Potential Vanilloid ◽  
Main Role ◽  
Trpv Channels ◽  
Gliovascular Unit ◽  
Transient Receptor ◽  
The Brain

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.

scholarly journals Pathological potential of astroglia

2008 ◽  
pp. S101-S110
Author(s):  
A Chvátal ◽  
M Anděrová ◽  
H Neprašová ◽  
I Prajerová ◽  
J Benešová ◽  
...  
Keyword(s):  
Glial Cells ◽  
Brain Parenchyma ◽  
Brain Diseases ◽  
Brain Pathology ◽  
Pathological Conditions ◽  
Recent Developments ◽  
Neurological Defect ◽  
Del Rio ◽  
The Brain ◽  
Brain Homeostasis

The pathological potential of glial cells was recognized already by Rudolf Virchow, Santiago Ramon y Cajal and Pio Del Rio-Ortega. Many functions and roles performed by astroglia in the healthy brain determine their involvement in brain diseases; as indeed any kind of brain insult does affect astrocytes, and their performance in pathological conditions, to a very large extent, determines the survival of the brain parenchyma, the degree of damage and neurological defect. Astrocytes being in general responsible for overall brain homeostasis are involved in virtually every form of brain pathology. Here we provide an overview of recent developments in identifying the role and mechanisms of the pathological potential of astroglia.

ATP-binding cassette transporters and neurodegenerative diseases

2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Abc Transporters ◽  
Brain Diseases ◽  
Atp Binding ◽  
Future Directions ◽  
Diverse Range ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Atp Binding Cassette

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.

Sign in / Sign up

Export Citation Format

Share Document