scholarly journals Physiology of Astroglial Excitability

Function ◽  
2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Alexei Verkhratsky ◽  
Alexey Semyanov ◽  
Robert Zorec
Keyword(s):  
Cyclic Amp ◽  
Second Messengers ◽  
Synaptic Connectivity ◽  
Neural Cells ◽  
Intracellular Signals ◽  
Multiple Receptors ◽  
Concentration Of Ions ◽  
The Central Nervous System ◽  
Evidence Review ◽  
Underlying Mechanisms

Abstract Classic physiology divides all neural cells into excitable neurons and nonexcitable neuroglia. Neuroglial cells, chiefly responsible for homeostasis and defense of the nervous tissue, coordinate their complex homeostatic responses with neuronal activity. This coordination reflects a specific form of glial excitability mediated by complex changes in intracellular concentration of ions and second messengers organized in both space and time. Astrocytes are equipped with multiple molecular cascades, which are central for regulating homeostasis of neurotransmitters, ionostasis, synaptic connectivity, and metabolic support of the central nervous system. Astrocytes are further provisioned with multiple receptors for neurotransmitters and neurohormones, which upon activation trigger intracellular signals mediated by Ca2+, Na+, and cyclic AMP. Calcium signals have distinct organization and underlying mechanisms in different astrocytic compartments thus allowing complex spatiotemporal signaling. Signals mediated by fluctuations in cytosolic Na+ are instrumental for coordination of Na+ dependent astrocytic transporters with tissue state and homeostatic demands. Astroglial ionic excitability may also involve K+, H+, and Cl−. The cyclic AMP signalling system is, in comparison to ions, much slower in targeting astroglial effector mechanisms. This evidence review summarizes the concept of astroglial intracellular excitability.

Involvement of second messengers and protein phosphorylation in astrocyte swelling

1992 ◽  
Vol 70 (S1) ◽  
pp. S362-S366 ◽  
Author(s):  
A. S. Bender ◽  
J. T. Neary ◽  
M. D. Norenberg
Keyword(s):  
Cyclic Amp ◽  
Protein Phosphorylation ◽  
Volume Regulation ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Astrocyte Swelling ◽  
Regulatory Processes ◽  
Intracellular Signals ◽  
Dependent Protein

In a hypoosmotic model of astrocyte swelling, we found that Ca2+ and intracellular signals such as diacylglycerol and inositol phosphate, as well as protein phosphorylation systems, are implicated in the generation and (or) modulation of volume regulatory processes. Cyclic AMP, which also has a significant effect on astrocyte volume regulation, in addition influences some of these second messengers.Key words: astrocyte, Ca2+-dependent protein kinases, Ca2+ influx, cell volume, cyclic AMP, inositol phosphates, protein phosphorylation.

scholarly journals Modulation of 3′,5′-cyclic AMP homeostasis in human platelets by coffee and individual coffee constituents

2014 ◽  
Vol 112 (9) ◽  
pp. 1427-1437 ◽  
Author(s):  
Gina A. Montoya ◽  
Tamara Bakuradze ◽  
Marion Eirich ◽  
Thomas Erk ◽  
Matthias Baum ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Mammalian Cells ◽  
Second Messengers ◽  
Human Platelets ◽  
Significant Inhibition ◽  
Intracellular Camp ◽  
Beneficial Effects ◽  
Underlying Mechanisms

3′,5′-Cyclic AMP (cAMP) is one of the most important second messengers in mammalian cells, mediating a multitude of diverse cellular signalling responses. Its homeostasis is primarily regulated by adenylate cyclases and phosphodiesterases (PDE), the activities of which are partially dependent on the downstream events of adenosine receptor signalling. The present study was conducted to determine whether coffee constituents other than caffeine can influence the homeostasis of intracellular cAMP in vitro and in vivo by evaluating the effects of selected constituents present in coffee, coffee brews and coffee extracts on platelet PDE activity. In addition, to evaluate the potential effects of these constituents on platelet cAMP concentrations and PDE activity in humans, a 7-week pilot intervention study with eight subjects was conducted. The subjects consumed a regular commercial coffee and a low-caffeine coffee at a rate of 750 ml/d for 2 weeks each. The in vivo results revealed a highly significant inhibition of PDE activity (P< 0·001) after coffee intervention that was not directly dependent on the caffeine content of coffee. Although our in vitro and in vivo findings suggest that caffeine plays some role in the modulation of platelet cAMP status, other natural and roasting-associated compounds such as pyrazines and other currently unidentified species also appear to contribute significantly. In conclusion, moderate consumption of coffee can modulate platelet PDE activity and cAMP concentrations in humans, which may contribute to the putative beneficial health effects of coffee. Further detailed mechanistic investigations will be required to substantiate these beneficial effects and to elucidate the underlying mechanisms.

scholarly journals Cannabidiol induces autophagy via ERK1/2 activation in neural cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Talita A. M. Vrechi ◽  
Anderson H. F. F. Leão ◽  
Ingrid B. M. Morais ◽  
Vanessa C. Abílio ◽  
Antonio W. Zuardi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Disorders ◽  
Molecular Mechanisms ◽  
Cannabis Sativa ◽  
Autophagic Flux ◽  
Neural Cells ◽  
Human Neuroblastoma ◽  
Trpv1 Receptor ◽  
The Central Nervous System ◽  
Catabolic Process

AbstractAutophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid present in Cannabis sativa. Many therapeutic actions have been linked to this compound, including autophagy activation. However, the precise underlying molecular mechanisms remain unclear, and the downstream functional significance of these actions has yet to be determined. Here, we investigated CBD-evoked effects on autophagy in human neuroblastoma SH-SY5Y and murine astrocyte cell lines. We found that CBD-induced autophagy was substantially reduced in the presence of CB1, CB2 and TRPV1 receptor antagonists, AM 251, AM 630 and capsazepine, respectively. This result strongly indicates that the activation of these receptors mediates the autophagic flux. Additionally, we demonstrated that CBD activates autophagy through ERK1/2 activation and AKT suppression. Interestingly, CBD-mediated autophagy activation is dependent on the autophagy initiator ULK1, but mTORC1 independent. Thus, it is plausible that a non-canonical pathway is involved. Our findings collectively provide evidence that CBD stimulates autophagy signal transduction via crosstalk between the ERK1/2 and AKT kinases, which represent putative regulators of cell proliferation and survival. Furthermore, our study sheds light on potential therapeutic cannabinoid targets that could be developed for treating neurodegenerative disorders.

scholarly journals The neuropathological impact of COVID-19: a review

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Ghadha Ibrahim Fouad
Keyword(s):  
Main Body ◽  
Respiratory Dysfunction ◽  
Behavior Understanding ◽  
Vital Functions ◽  
Global Issue ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
Neural Disorders ◽  
High Adaptation ◽  
Viral Outbreak

Abstract Background The Coronavirus disease 2019 (COVID-19) outbreak has become a challenging global issue after its emergence in December 2019. Due to the high adaptation of the virus, COVID-19 demonstrated a high transmission and infectivity potentials. Several studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induce deleterious neurological manifestations through interacting with the central nervous system (CNS). Main body The neuroinvasive potential of SARS-CoV-2 might contribute to its fatal behavior. Understanding the underlying mechanisms of this novel neuropathogen might contribute to the development of effective therapeutic strategies. The manifestations of neural damage in COVID-19 patients ranged from headache to severe encephalopathy and progression of preexisting neural disorders, it is speculated that neuroinvasion is strongly linked to the fatal respiratory dysfunction. The underlying neuropathological impact of emerging pneumonia (COVID-19) is still unclear. Conclusion This review demonstrated the urgent need to understand the neuropathology of COVID-19, to manage the current borderless viral outbreak of SARS-CoV-2 and its comorbidities. Moreover, SARS-CoV-2 could be regarded as an opportunistic neuropathogen that affects several vital functions in the human body.

scholarly journals Infectious disease-associated encephalopathies

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Maria C. Barbosa-Silva ◽  
Maiara N. Lima ◽  
Denise Battaglini ◽  
Chiara Robba ◽  
Paolo Pelosi ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Cognitive Deficits ◽  
Brain Function ◽  
Cell Activation ◽  
Therapeutic Strategies ◽  
Barrier Dysfunction ◽  
Glial Cell Activation ◽  
The Central Nervous System ◽  
Underlying Mechanisms

AbstractInfectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood–brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation. Graphic abstract

scholarly journals Bicarbonate Evokes Reciprocal Changes in Intracellular Cyclic di-GMP and Cyclic AMP Levels in Pseudomonas aeruginosa

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 519
Author(s):  
Kasidid Ruksakiet ◽  
Balázs Stercz ◽  
Gergő Tóth ◽  
Pongsiri Jaikumpun ◽  
Ilona Gróf ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Biofilm Formation ◽  
Second Messengers ◽  
Brain Heart Infusion ◽  
Ambient Air ◽  
Dependent Manner ◽  
Environmental Signals ◽  
Common Causes ◽  
Camp Levels

The formation of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) is one of the most common causes of morbidity and mortality in CF patients. Cyclic di-GMP and cyclic AMP are second messengers regulating the bacterial lifestyle transition in response to environmental signals. We aimed to investigate the effects of extracellular pH and bicarbonate on intracellular c-di-GMP and cAMP levels, and on biofilm formation. P. aeruginosa was inoculated in a brain–heart infusion medium supplemented with 25 and 50 mM NaCl in ambient air (pH adjusted to 7.4 and 7.7 respectively), or with 25 and 50 mM NaHCO3 in 5% CO2 (pH 7.4 and 7.7). After 16 h incubation, c-di-GMP and cAMP were extracted and their concentrations determined. Biofilm formation was investigated using an xCelligence real-time cell analyzer and by crystal violet assay. Our results show that HCO3− exposure decreased c-di-GMP and increased cAMP levels in a dose-dependent manner. Biofilm formation was also reduced after 48 h exposure to HCO3−. The reciprocal changes in second messenger concentrations were not influenced by changes in medium pH or osmolality. These findings indicate that HCO3− per se modulates the levels of c-di-GMP and cAMP, thereby inhibiting biofilm formation and promoting the planktonic lifestyle of the bacteria.

scholarly journals The Molecular Biology of Brain Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Gazanfar Rahmathulla ◽  
Steven A. Toms ◽  
Robert J. Weil
Keyword(s):  
Molecular Biology ◽  
Brain Metastasis ◽  
Targeted Drug Delivery ◽  
Rapid Expansion ◽  
Genetic Mechanisms ◽  
The Central Nervous System ◽  
Targeted Drug ◽  
Underlying Mechanisms ◽  
The Brain ◽  
New Location

Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancers. Various crucial interactions between the brain environment and tumor cells take place during the development of the cancer at its new location. The rapid expansion in molecular biology and genetics has advanced our knowledge of the underlying mechanisms involved, from invasion to final colonization of new organ tissues. Understanding the various events occurring at each stage should enable targeted drug delivery and individualized treatments for patients, with better outcomes and fewer side effects. This paper summarizes the principal molecular and genetic mechanisms that underlie the development of brain metastasis (BrM).

scholarly journals Influences of Morphine on the Spontaneous and Evoked Excitatory Postsynaptic Currents in Lateral Amygdala of Rats

2016 ◽  
pp. 165-169 ◽  
Author(s):  
J.-J. ZHANG ◽  
X.-D. LIU ◽  
L.-C. YU
Keyword(s):  
Synaptic Transmission ◽  
Excitatory Synaptic Transmission ◽  
Morphine Treatment ◽  
Lateral Amygdala ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Acute morphine exposure induces antinociceptive activity, but the underlying mechanisms in the central nervous system are unclear. Using whole-cell patch clamp recordings, we explore the role of morphine in the modulation of excitatory synaptic transmission in lateral amygdala neurons of rats. The results demonstrate that perfusion of 10 μM of morphine to the lateral amygdala inhibits the discharge frequency significantly. We further find that there are no significant influences of morphine on the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). Interestingly, morphine shows no marked influence on the evoked excitatory postsynaptic currents (eEPSCs) in the lateral amygdala neurons. These results indicate that acute morphine treatment plays an important role in the modulation on the excitatory synaptic transmission in lateral amygdala neurons of rats.

scholarly journals The Effects and Underlying Mechanisms of Cell Therapy on Blood-Brain Barrier Integrity After Ischemic Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1213-1226
Author(s):  
Li Gao ◽  
Zhenghong Song ◽  
Jianhua Mi ◽  
Pinpin Hou ◽  
Chong Xie ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cell Therapy ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Neural Cells ◽  
Promising Tool ◽  
Cell Based Therapy ◽  
Blood Brain ◽  
Underlying Mechanisms

Ischemic stroke is one of the main causes of mortality and disability worldwide. However, efficient therapeutic strategies are still lacking. Stem/progenitor cell-based therapy, with its vigorous advantages, has emerged as a promising tool for the treatment of ischemic stroke. The mechanisms involve new neural cells and neuronal circuitry formation, antioxidation, inflammation alleviation, angiogenesis, and neurogenesis promotion. In the past decades, in-depth studies have suggested that cell therapy could promote vascular stabilization and decrease blood-brain barrier (BBB) leakage after ischemic stroke. However, the effects and underlying mechanisms on BBB integrity induced by the engrafted cells in ischemic stroke have not been reviewed yet. Herein, we will update the progress in research on the effects of cell therapy on BBB integrity after ischemic stroke and review the underlying mechanisms. First, we will present an overview of BBB dysfunction under the ischemic condition and cells engraftment for ischemic treatment. Then, we will summarize and discuss the current knowledge about the effects and underlying mechanisms of cell therapy on BBB integrity after ischemic stroke. In particular, we will review the most recent studies in regard to the relationship between cell therapy and BBB in tissue plasminogen activator (t-PA)-mediated therapy and diabetic stroke.

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