Antioxidant and bioenergetic coupling between neurons and astrocytes

2012 ◽  
Vol 443 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Seila Fernandez-Fernandez ◽  
Angeles Almeida ◽  
Juan P. Bolaños
Keyword(s):  
Nitrosative Stress ◽  
Pentose Phosphate ◽  
Therapeutic Interventions ◽  
Biochemical Mechanism ◽  
Intercellular Coupling ◽  
Antioxidant Defence ◽  
Oxidative And Nitrosative Stress ◽  
Novel Targets ◽  
The Brain ◽  
Reduced State

Oxidative and nitrosative stress underlie the pathogenesis of a broad range of human diseases, in particular neurodegenerative disorders. Within the brain, neurons are the cells most vulnerable to excess reactive oxygen and nitrogen species; their survival relies on the antioxidant protection promoted by neighbouring astrocytes. However, neurons are also intrinsically equipped with a biochemical mechanism that links glucose metabolism to antioxidant defence. Neurons actively metabolize glucose through the pentose phosphate pathway, which maintains the antioxidant glutathione in its reduced state, hence exerting neuroprotection. This process is tightly controlled by a key glycolysis-promoting enzyme and is dependent on an appropriate supply of energy substrates from astrocytes. Thus brain bioenergetic and antioxidant defence is coupled between neurons and astrocytes. A better understanding of the regulation of this intercellular coupling should be important for identifying novel targets for future therapeutic interventions.

scholarly journals The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 644
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Michał Bijak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative And Nitrosative Stress ◽  
Peripheral Blood Mononuclear ◽  
Taqman Gene Expression Assay ◽  
The Brain

Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.

scholarly journals MicroRNAs, Multiple Sclerosis and Depression

2021 ◽  
Vol 22 (15) ◽  
pp. 7802
Author(s):  
Hsiuying Wang
Keyword(s):  
Multiple Sclerosis ◽  
Depressive Disorders ◽  
Nitrosative Stress ◽  
Mirna Regulation ◽  
Oxidative And Nitrosative Stress ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Patients Experience ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects the brain and spinal cord. There are several disease courses in MS including relapsing–remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). Up to 50% of MS patients experience depressive disorders. Major depression (MD) is a serious comorbidity of MS. Many dysfunctions including neuroinflammation, peripheral inflammation, gut dysbiosis, chronic oxidative and nitrosative stress, and neuroendocrine and mitochondrial abnormalities may contribute to the comorbidity between MS and MD. In addition to these actions, medical treatment and microRNA (miRNA) regulation may also be involved in the mechanisms of the comorbidity between MS and MD. In the study, I review many common miRNA biomarkers for both diseases. These common miRNA biomarkers may help further explore the association between MS and MD.

scholarly journals Effects of agmatine on chlorpromazine-induced neuronal injury in rat

2018 ◽  
Vol 87 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Bratislav Dejanovic ◽  
Vesna Vukovic-Dejanovic ◽  
Milica Ninkovic ◽  
Irena Lavrnja ◽  
Ivana Stojanovic ◽  
...  
Keyword(s):  
Nitrosative Stress ◽  
Combined Treatment ◽  
Brain Regions ◽  
Antioxidant Defence ◽  
Superoxide Anion Production ◽  
Beneficial Effects ◽  
Antioxidant Defence System ◽  
Oxide Concentration ◽  
Nitric Oxide Concentration ◽  
The Brain

This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosative stress development in the brain of Wistar rats during subacute chlorpromazine treatment. The animals were divided into control (0.9% saline), chlorpromazine (38.7 mg/kg b.w.), chlorpromazine+agmatine (agmatine 75 mg/kg b.w. immediately after chlorpromazine, 38.7 mg/kg b.w. i.p.) and agmatine (75 mg/kg b.w.) groups. All the tested substances were administered intraperitoneally for 15 consecutive days and the rats were sacrificed by decapitation on day 15. Subacute administration of chlorpromazine resulted in increased lipid peroxidation, nitric oxide concentration and superoxide anion production, while completely damaging the antioxidant defence system in the cerebral cortex, striatum, and hippocampus. However, the combined treatment with chlorpromazine and agmatine significantly attenuated the oxidative/nitrosative stress indices and restored the antioxidant capacity to the control values in all of the examined brain regions. Western blot analysis supported biochemical findings in all groups, but the most notable changes were found in the hippocampus. Our results suggest potentially beneficial effects of agmatine, which may be useful in the modified antioxidant approach in chlorpromazine-therapy.

Malfunctions of the conjugated system “Restoring thiols – Nitrogen oxide” with acute cerebrovascular accident and possible correction

2015 ◽  
Vol 17 (4) ◽  
Author(s):  
S. V. Horbachova ◽  
I. F. Bielenichev ◽  
L. I. Kucherenko
Keyword(s):  
Brain Tissue ◽  
Nitrosative Stress ◽  
Free Radical Oxidation ◽  
Thiol Group ◽  
Oxidative And Nitrosative Stress ◽  
Radical Oxidation ◽  
Active Mobilization ◽  
Common Carotid Arteries ◽  
The Brain ◽  
Stress Simulation

<p>Experimental acute ischemic stroke was modeled by bilateral occlusion of the common carotid arteries in rats. Antioxidant system in the brain tissue was evaluated by the activity of key enzymes of thiol and disulfide indicators<br />nitrosative stress. Simulation of acute ischemic accompanied by violation of the thiol-disulfide balance and increased nitrotyrosine levels, indicating that the development of oxidative and nitrosative stress in brain tissue. It is established<br />that the use of thiol-containing antioxidants – Thiotriazoline and Angiolin set the highest possible ratio between the levels of reduced and oxidized thiol groups and glutathione, which indicates that the active mobilization of thioldisulfide<br />system in the neutralization products of free-radical oxidation. Identified effects of the drugs used due to the presence in their structure of the thiol group, which contributes to the normalization of the glutathione system in conditions of oxidative stress.</p>

scholarly journals Immunohistochemical Study of Antioxidant Enzymes Regulated by Nrf2 in the Models of Epileptic Seizures (KA and PTZ)

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
María Fernanda Munguía-Martínez ◽  
Concepción Nava-Ruíz ◽  
Amairani Ruíz-Díaz ◽  
Araceli Díaz-Ruíz ◽  
Petra Yescas-Gómez ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Nitrosative Stress ◽  
Epileptic Seizures ◽  
Experimental Models ◽  
Immunohistochemical Expression ◽  
Oxidative And Nitrosative Stress ◽  
Stress Effects ◽  
Spontaneous Seizures ◽  
The Brain

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures due to an imbalance between cerebral excitability and inhibition, with a tendency towards uncontrolled excitability. Epilepsy has been associated with oxidative and nitrosative stress due to prolonged neuronal hyperexcitation and loss neurons during seizures. The experimental animal models report level of ATP diminished and increase in lipid peroxidation, catalase, and glutathione altered activity in the brain. We studied the immunohistochemical expression and localization of antioxidant enzymes GPx, SOD, and CAT in the rat brains treated with KA and PTZ. A significant decrease was observed in the number of immunoreactive cells to GPx, without significant changes for SOD and CAT in KA-treated rats, and decrease in the number of immunoreactive cells to SOD, without significant changes for GPx and only CAT in PTZ-treated rats. Evident immunoreactivity of GPx, SOD, and CAT was observed mainly in astrocytes and neurons of the hippocampal brain region in rats exposed at KA; similar results were observed in rats treated with PTZ at the first hours. These results provide evidence supporting the role of activation of the Nrf2 antioxidant system pathway against oxidative stress effects in the experimental models of epileptic seizures.

scholarly journals The Effect of Impaired Polyamine Transport on Pneumococcal Transcriptome

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1322
Author(s):  
Mary F. Nakamya ◽  
Moses B. Ayoola ◽  
Leslie A. Shack ◽  
Edwin Swiatlo ◽  
Bindu Nanduri
Keyword(s):  
Stress Responses ◽  
Nitrosative Stress ◽  
Sugar Metabolism ◽  
Pentose Phosphate ◽  
Therapeutic Interventions ◽  
Expression Of Genes ◽  
Polyamine Transport ◽  
Novel Target ◽  
Pentose Phosphate Pathways

Infections due to Streptococcus pneumoniae, a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. Pathogenic mechanisms that allow successful adaption and persistence in the host could be potential innovative therapeutic targets. Polyamines are ubiquitous polycationic molecules that regulate many cellular processes. We previously reported that deletion of polyamine transport operon potABCD, which encodes a putrescine/spermidine transporter (∆potABCD), resulted in an unencapsulated attenuated phenotype. Here, we characterize the transcriptome, metabolome, and stress responses of polyamine transport-deficient S. pneumoniae. Compared with the wild-type strain, the expression of genes involved in oxidative stress responses and the nucleotide sugar metabolism was reduced, while expression of genes involved in the Leloir, tagatose, and pentose phosphate pathways was higher in ΔpotABCD. A metabolic shift towards the pentose phosphate pathway will limit the synthesis of precursors of capsule polysaccharides. Metabolomics results show reduced levels of glutathione and pyruvate in the mutant. Our results also show that the potABCD operon protects pneumococci against hydrogen peroxide and nitrosative stress. Our findings demonstrate the importance of polyamine transport in pneumococcal physiology that could impact in vivo fitness. Thus, polyamine transport in pneumococci represents a novel target for therapeutic interventions.

scholarly journals Polyamine Transport Is Required for Stress Responses and Capsule Production in Streptococcus Pneumoniae

2021 ◽  
Author(s):  
Mary F. Nakamya ◽  
Moses B. Ayoola ◽  
Leslie A. Shack ◽  
Edwin Swiatlo ◽  
Bindu Nanduri
Keyword(s):  
Streptococcus Pneumoniae ◽  
Stress Responses ◽  
Nitrosative Stress ◽  
Pentose Phosphate ◽  
Therapeutic Interventions ◽  
Central Metabolism ◽  
Expression Of Genes ◽  
Capsule Production ◽  
Polyamine Transport ◽  
Novel Target

Abstract Infections due to Streptococcus pneumoniae, a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genetic plasticity, antibiotic resistance, limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions. Pathogenic systems that allow successful adaption and persistence in the host could be potential innovative targets for mediations. Polyamines are ubiquitous polycationic molecules and regulate many cellular processes. We previously reported that deletion of potABCD, an operon that encodes a putrescine/spermidine transporter (∆potABCD), resulted in an un-encapsulated attenuated phenotype. Here we characterize the transcriptome, metabolome, and stress responses of S. pneumoniae that is dependent on the polyamine transporter. Expression of genes involved in oxidative stress responses and the central metabolism was reduced while that of genes involved in the Leloir, tagatose, and pentose phosphate pathways was increased in ΔpotABCD. Downregulation of genes of the central metabolism will reduce production of precursors of capsule polysaccharides. Metabolomics results show reduced glutathione and pyruvate levels in the mutant. We also show that the potABCD operon protects pneumococci against hydrogen peroxide and nitrosative stress. These results show the importance of the potABCD operon and polyamine transport in pneumococcal physiology and fitness that represents a novel target for therapeutic interventions.

Linking glycolysis with oxidative stress in neural cells: a regulatory role for nitric oxide

2007 ◽  
Vol 35 (5) ◽  
pp. 1224-1227 ◽  
Author(s):  
J.P. Bolaños ◽  
A. Herrero-Mendez ◽  
S. Fernandez-Fernandez ◽  
A. Almeida
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Soluble Guanylate Cyclase ◽  
Cell Signalling ◽  
Glucose Consumption ◽  
Mitochondrial Respiratory Chain ◽  
Pentose Phosphate ◽  
Neural Cells ◽  
Cellular Functions ◽  
Oxidative And Nitrosative Stress

NO (nitric oxide) participates in a considerable number of physiological functions. At the biochemical level, most of its actions can be ascribed to its ability to bind, and activate, soluble guanylate cyclase. However, mounting evidence now strongly suggests that the NO-mediated inhibition of cytochrome c oxidase, the terminal complex of the mitochondrial respiratory chain, may be a further step of a cell signalling process involved in the regulation of important cellular functions. In most cells, including neurons and astrocytes, NO reversibly, and irreversibly, modulates O2 consumption, a phenomenon through which NO signals certain pathways relevant for neuronal survival. Here, we propose that besides the control of mitochondrial bioenergetics, NO finely modulates the balance between glucose consumption through the glycolytic pathway and the pentose phosphate pathway in neurons. This may have implications for our understanding of the mechanisms of neurodegeneration due to oxidative and nitrosative stress.

scholarly journals Oxidative stress and post-stroke depression

2018 ◽  
Vol 16 (3) ◽  
pp. 249-253 ◽  
Author(s):  
D. Komsiyska
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Nitrosative Stress ◽  
Multifactorial Disease ◽  
Oxygen Utilization ◽  
Oxidative And Nitrosative Stress ◽  
Post Stroke ◽  
Mental Diseases ◽  
Post Stroke Depression ◽  
The Brain

The topic of post-stroke depression etiology is reviewed in two main approaches. Some suggest that post-stroke depression is caused by the brain damage itself. On the contrary, others assume that this is a psychologic response to injuries or loss. Many discoveries can be examined as evidence for both the physiological and psychosocial mechanism of post-stroke depression. The two methods are not self-excluding, but instead describe post-stroke depression as a complex and multifactorial disease with interactions between the physiological and environmental factor. One hypothesis about depression occurrence is the inflammatory, oxidative and nitrosative stress (IO&NS) depression theory. Oxidative stress mechanisms are implied in the pathogenesis of mental diseases. The brain is considered particularly vulnerable to oxidative damage, due to its relatively high oxygen utilization and thus generation of free radical subordinate products, its modest antioxidant protections and its lipid-rich resistance.

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