scholarly journals Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis

2021 ◽  
Vol 22 (16) ◽  
pp. 9028
Author(s):  
Toya Okawa ◽  
Kurumi Hara ◽  
Momoko Goto ◽  
Moe Kikuchi ◽  
Masataka Kogane ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Brain Parenchyma ◽  
Aminobutyric Acid ◽  
Potential Mechanism ◽  
Initial Stage ◽  
Glutamate Production ◽  
The Central Nervous System ◽  
The Brain ◽  
Glutamine Production

The second messenger 2′3′-cyclic-GMP-AMP (cGAMP) is thought to be transmitted from brain carcinomas to astrocytes via gap junctions, which functions to promote metastasis in the brain parenchyma. In the current study, we established a method to introduce cGAMP into astrocytes, which simulates the state of astrocytes that have been invaded by cGAMP around tumors. Astrocytes incorporating cGAMP were analyzed by metabolomics, which demonstrated that cGAMP increased glutamate production and astrocyte secretion. The same trend was observed for γ-aminobutyric acid (GABA). Conversely, glutamine production and secretion were decreased by cGAMP treatment. Due to the fundamental role of astrocytes in regulation of the glutamine–glutamate cycle, such metabolic changes may represent a potential mechanism and therapeutic target for alteration of the central nervous system (CNS) environment and the malignant transformation of brain carcinomas.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 3

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 125-134
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Inflammatory Reactions ◽  
Mental Diseases ◽  
The Central Nervous System ◽  
The Brain

Background: at present, the important role of the monocyte-macrophage link of immunity in the pathogenesis of mental diseases has been determined. In the first and second parts of our review, the cellular and molecular mechanisms of activation of monocytes/macrophages, which secreting proinflammatory CD16 receptors, cytokines, chemokines and receptors to them, in the development of systemic immune inflammation in the pathogenesis of somatic diseases and mental disorders, including schizophrenia, bipolar affective disorder (BAD) and depression were analyzed. The association of high levels of proinflammatory activity of monocytes/macrophages in patients with mental disorders with somatic comorbidity, including immune system diseases, is shown. It is known that proinflammatory monocytes of peripheral blood, as a result of violation of the integrity of the hematoencephalic barrier can migrate to the central nervous system and activate the resident brain cells — microglia, causing its activation. Activation of microglia can lead to the development of neuroinammation and neurodegenerative processes in the brain and, as a result, to cognitive disorders. The aim of review: to analyze the results of the main scientific studies concerning the role of cellular and molecular mechanisms of peripheral blood monocytes interaction with microglial cells and platelets in the development of neuroinflammation in the pathogenesis of mental disorders, including Alzheimer’s disease (AD). Material and methods: keywords “mental disorders, AD, proinflammatory monocytes, microglia, neuroinflammation, cytokines, chemokines, cell adhesion molecules, platelets, microvesicles” were used to search for articles of domestic and foreign authors published over the past 30 years in the databases PubMed, eLibrary, Science Direct and EMBASE. Conclusion: this review analyzes the results of studies which show that monocytes/macrophages and microglia have similar gene expression profiles in schizophrenia, BAD, depression, and AD and also perform similar functions: phagocytosis and inflammatory responses. Monocytes recruited to the central nervous system stimulate the increased production of proinflammatory cytokines IL-1, IL-6, tumor necrosis factor alpha (TNF-α), chemokines, for example, MCP-1 (Monocyte chemotactic protein-1) by microglial cells. This promotes the recruitment of microglial cells to the sites of neuronal damage, and also enhances the formation of the brain protein beta-amyloid (Aβ). The results of modern studies are presented, indicating that platelets are involved in systemic inflammatory reactions, where they interact with monocytes to form monocyte-platelet aggregates (MTA), which induce the activation of monocytes with a pro inflammatory phenotype. In the last decade, it has been established that activated platelets and other cells of the immune system, including monocytes, detached microvesicles (MV) from the membrane. It has been shown that MV are involved as messengers in the transport of biologically active lipids, cytokines, complement, and other molecules that can cause exacerbation of systemic inflammatory reactions. The presented review allows us to expand our knowledge about the cellular and molecular aspects of the interaction of monocytes/macrophages with microglial cells and platelets in the development of neuroinflammation and cognitive decline in the pathogenesis of mental diseases and in AD, and also helps in the search for specific biomarkers of the clinical severity of mental disorder in patients and the prospects for their response to treatment.

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

scholarly journals Immune cells and CNS physiology: Microglia and beyond

2018 ◽  
Vol 216 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Geoffrey T. Norris ◽  
Jonathan Kipnis
Keyword(s):  
Central Nervous System ◽  
Immune Cells ◽  
Brain Function ◽  
Brain Parenchyma ◽  
The Body ◽  
Immune Repertoire ◽  
Perivascular Macrophages ◽  
The Central Nervous System ◽  
Cns Immunity ◽  
The Brain

Recent advances have directed our knowledge of the immune system from a narrative of “self” versus “nonself” to one in which immune function is critical for homeostasis of organs throughout the body. This is also the case with respect to the central nervous system (CNS). CNS immunity exists in a segregated state, with a marked partition occurring between the brain parenchyma and meningeal spaces. While the brain parenchyma is patrolled by perivascular macrophages and microglia, the meningeal spaces are supplied with a diverse immune repertoire. In this review, we posit that such partition allows for neuro–immune crosstalk to be properly tuned. Convention may imply that meningeal immunity is an ominous threat to brain function; however, recent studies have shown that its presence may instead be a steady hand directing the CNS to optimal performance.

scholarly journals Immune System in the Brain: A Modulatory Role on Dendritic Spine Morphophysiology?

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Oscar Kurt Bitzer-Quintero ◽  
Ignacio González-Burgos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Dendritic Spines ◽  
Cell Lineage ◽  
Myeloid Cell ◽  
Brain Parenchyma ◽  
Immune Mediators ◽  
The Central Nervous System ◽  
The Brain

The central nervous system is closely linked to the immune system at several levels. The brain parenchyma is separated from the periphery by the blood brain barrier, which under normal conditions prevents the entry of mediators such as activated leukocytes, antibodies, complement factors, and cytokines. The myeloid cell lineage plays a crucial role in the development of immune responses at the central level, and it comprises two main subtypes: (1) resident microglia, distributed throughout the brain parenchyma; (2) perivascular macrophages located in the brain capillaries of the basal lamina and the choroid plexus. In addition, astrocytes, oligodendrocytes, endothelial cells, and, to a lesser extent, neurons are implicated in the immune response in the central nervous system. By modulating synaptogenesis, microglia are most specifically involved in restoring neuronal connectivity following injury. These cells release immune mediators, such as cytokines, that modulate synaptic transmission and that alter the morphology of dendritic spines during the inflammatory process following injury. Thus, the expression and release of immune mediators in the brain parenchyma are closely linked to plastic morphophysiological changes in neuronal dendritic spines. Based on these observations, it has been proposed that these immune mediators are also implicated in learning and memory processes.

scholarly journals Unexpected intracranial location of a Cephenemyia stimulator larva in a roe deer, Capreolus capreolus, revealed by computed tomography

2021 ◽  
Vol 33 ◽  
pp. 1-7
Author(s):  
Luis E. Fidalgo ◽  
Ana M. López-Beceiro ◽  
Carlos Martínez-Carrasco ◽  
Noelia Caparrós-Fontarosa ◽  
Antonio Sánchez ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Central Nervous System ◽  
Roe Deer ◽  
Capreolus Capreolus ◽  
Brain Parenchyma ◽  
Anatomical Location ◽  
Migration Route ◽  
The Central Nervous System ◽  
Hemorrhagic Lesion ◽  
The Brain

In this study we describe the finding of a Cephenemyia stimulator larva in the brain of a roe deer (Capreolus capreolus) after performing a computed tomography (CT) scan of its head. Despite this anatomical location of oestrid larvae could be relatively frequent in other genera, such as Oestrus, to our knowledge, this is the first reported case involving the genus Cephenemyia. Concretely, a second-instar C. stimulator larvae was found in the basis of the cranium. The location of a macroscopic hemorrhagic lesion involving the brain parenchyma peripheral to the location of the larva suggests that tissue colonization occurred before the animal was hunted. Since no detectable alterations or damage to the cranial bones were observed, we suggest a possible larval migration route drilling the skull bones. Finally, we propose the use of the term “neuromyiasis” to be referred to the invasion of the central nervous system by dipteran larvae, particularly oestrids.

Neurochemicals and respiratory control during development

1989 ◽  
Vol 67 (1) ◽  
pp. 1-13 ◽  
Author(s):  
I. R. Moss ◽  
J. G. Inman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Respiratory Control ◽  
Perinatal Period ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Respiratory Effects ◽  
The Central Nervous System ◽  
Plastic Process

During ontogeny, the central nervous system undergoes neuronal growth, regression, and remodeling. The development of neurotransmitter and modulator systems is a plastic process with individual temporal characteristics for each system. These characteristics include the synthesis, degradation, or uptake of neurochemicals and, largely independently, the appearance of their receptors. Message transmission during ontogeny is compounded by the variable development of these systems and by the coexistence and cofunction among these chemicals. Nine neurochemical systems are discussed: adenosine, gamma-aminobutyric acid, opioids, prostaglandins, serotonin, progesterone, substance P, thyrotropin-releasing hormone, and the catecholamines. The possible role of each of these in natural perinatal respiratory control is evaluated according to predetermined criteria. These include the presence of a substance system in respiratory-related regions, physiologically appropriate changes in its concentration in these regions, elicitation of respiratory effects by agonists and antagonists, and abolition with an antagonist of the effect of a substance during its presumed activation by a physiological process. It is suggested that excessive levels of suppressant neuromodulators or an imbalance among neurochemicals can partly explain the special features of respiratory control in the perinatal period.

The role of metabolites and the role of histo-hematological barriers in the regulation of body functions. (End)

1937 ◽  
Vol 33 (5) ◽  
pp. 523-532
Author(s):  
L. S. Stern
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
General Circulation ◽  
Physiological State ◽  
The State ◽  
The Central Nervous System ◽  
The Brain ◽  
Physiological Systems

Evaluation of the results obtained in the study of the effect of cerebrospinal fluid on various physiological systems is complicated by the fact that the composition of the cerebrospinal fluid depends to a large extent on the state of the blood-brain barrier, and thus reflects not only a certain physiological state of the central nervous system. There is no doubt that the metabolic products of the brain, secreted into the cerebrospinal fluid, exert their effect not only on the activity of various parts of the brain and on the coordination of their functions, but due to the rapid transition of these substances from the cerebrospinal fluid into the general circulation, they also affect as a humoral a factor on the function of other physiological systems, as it was revealed in a number of experiments carried out in recent years in our laboratories. For example, it turned out that under various influences (direct irritation of the central nervous system in experimental epilepsy, irritation of the sensory nerves associated with severe pain, traumatic shock, toxemic or chemical shock, as well as starvation, prolonged insomnia, etc.) - substances appear in the cerebrospinal fluid that affect the state and activity of the cardiovascular system, the tone of smooth muscles, the excitability of the central nervous system, etc. These are the results of the work of our employees: Zeitlin, Weiss, Harles, Voskresensky, Gromakovskaya , Bazarova, Gotsman, Komarova and others. Work in this direction continues at the present time.

Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1757-1769 ◽  
Author(s):  
C. Olivier ◽  
I. Cobos ◽  
E.M. Perez Villegas ◽  
N. Spassky ◽  
B. Zalc ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chick Embryo ◽  
Embryonic Development ◽  
Progenitor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Chick Brain ◽  
The Central Nervous System ◽  
The Brain

Oligodendrocytes are the myelin-forming cells in the central nervous system. In the brain, oligodendrocyte precursors arise in multiple restricted foci, distributed along the caudorostral axis of the ventricular neuroepithelium. In chick embryonic hind-, mid- and caudal forebrain, oligodendrocytes have a basoventral origin, while in the rostral fore-brain oligodendrocytes emerge from alar territories (Perez Villegas, E. M., Olivier, C., Spassky, N., Poncet, C., Cochard, P., Zalc, B., Thomas, J. L. and Martinez, S. (1999) Dev. Biol. 216, 98–113). To investigate the respective territories colonized by oligodendrocyte progenitor cells that originate from either the basoventral or alar foci, we have created a series of quail-chick chimeras. Homotopic chimeras demonstrate clearly that, during embryonic development, oligodendrocyte progenitors that emerge from the alar anterior entopeduncular area migrate tangentially to invade the entire telencephalon, whereas those from the basal rhombomeric foci show a restricted rostrocaudal distribution and colonize only their rhombomere of origin. Heterotopic chimeras indicate that differences in the migratory properties of oligodendroglial cells do not depend on their basoventral or alar ventricular origin. Irrespective of their origin (basal or alar), oligodendrocytes migrate only short distances in the hindbrain and long distances in the prosencephalon. Furthermore, we provide evidence that, in the developing chick brain, all telencephalic oligodendrocytes originate from the anterior entopeduncular area and that the prominent role of anterior entopeduncular area in telencephalic oligodendrogenesis is conserved between birds and mammals.

Arachidonic Acid Derivatives and Neuroinflammation

2021 ◽  
Vol 20 ◽  
Author(s):  
Era Gorica ◽  
Vincenzo Calderone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Inflammatory Responses ◽  
The Central Nervous System ◽  
The Brain ◽  
Arachidonic Acid Derivatives

: Neuroinflammation is characterized by dysregulated inflammatory responses localized within the brain and spinal cord. Neuroinflammation plays a pivotal role in the onset of several neurodegenerative disorders and is considered a typical feature of these disorders. Microglia perform primary immune surveillance and macrophage-like activities within the central nervous system. Activated microglia are predominant players in the central nervous system response to damage related to stroke, trauma, and infection. Moreover, microglial activation per se leads to a proinflammatory response and oxidative stress. During the release of cytokines and chemokines, cyclooxygenases and phospholipase A2 are stimulated. Elevated levels of these compounds play a significant role in immune cell recruitment into the brain. Cyclic phospholipase A2 plays a fundamental role in the production of prostaglandins by releasing arachidonic acid. In turn, arachidonic acid is biotransformed through different routes into several mediators that are endowed with pivotal roles in the regulation of inflammatory processes. Some experimental models of neuroinflammation exhibit an increase in cyclic phospholipase A2, leukotrienes, and prostaglandins such as prostaglandin E2, prostaglandin D2, or prostacyclin. However, findings on the role of the prostacyclin receptors have revealed that their signalling suppresses Th2-mediated inflammatory responses. In addition, other in vitro evidence suggests that prostaglandin E2 may inhibit the production of some inflammatory cytokines, attenuating inflammatory events such as mast cell degranulation or inflammatory leukotriene production. Based on these conflicting experimental data, the role of arachidonic acid derivatives in neuroinflammation remains a challenging issue.

scholarly journals Physiology of Microglia

2011 ◽  
Vol 91 (2) ◽  
pp. 461-553 ◽  
Author(s):  
Helmut Kettenmann ◽  
Uwe-Karsten Hanisch ◽  
Mami Noda ◽  
Alexei Verkhratsky
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cell ◽  
Brain Parenchyma ◽  
Microglial Cells ◽  
Activation Process ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Cellular Compartments ◽  
The Brain

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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