scholarly journals Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 577 ◽  
Author(s):  
José Bono-Yagüe ◽  
Ana Pilar Gómez-Escribano ◽  
José María Millán ◽  
Rafael Pascual Vázquez-Manrique
Keyword(s):  
Oxidative Stress ◽  
Huntington Disease ◽  
Basic Research ◽  
Medical Intervention ◽  
Causative Gene ◽  
The Many ◽  
Low Prevalence ◽  
The Brain ◽  
Positive Results ◽  
Delay Progression

Huntington disease (HD) is a neurodegenerative condition and one of the so-called rare or minority diseases, due to its low prevalence (affecting 1–10 of every 100,000 people in western countries). The causative gene, HTT, encodes huntingtin, a protein with a yet unknown function. Mutant huntingtin causes a range of phenotypes, including oxidative stress and the activation of microglia and astrocytes, which leads to chronic inflammation of the brain. Although substantial efforts have been made to find a cure for HD, there is currently no medical intervention able to stop or even delay progression of the disease. Among the many targets of therapeutic intervention, oxidative stress and inflammation have been extensively studied and some clinical trials have been promoted to target them. In the present work, we review the basic research on oxidative stress in HD and the strategies used to fight it. Many of the strategies to reduce the phenotypes associated with oxidative stress have produced positive results, yet no substantial functional recovery has been observed in animal models or patients with the disease. We discuss possible explanations for this and suggest potential ways to overcome it.

Redox-sensitive GFP to monitor oxidative stress in neurodegenerative diseases

2017 ◽  
Vol 28 (2) ◽  
pp. 133-144 ◽  
Author(s):  
Sonia Esposito ◽  
Alessandra Masala ◽  
Simona Sanna ◽  
Mauro Rassu ◽  
Viengsavanh Pimxayvong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Fluorescent Proteins ◽  
Neuronal Population ◽  
Adult Onset ◽  
Causative Gene ◽  
Cell Compartments ◽  
Redox Change ◽  
The Many ◽  
Key Events

AbstractRedox processes are key events in the degenerative cascade of many adult-onset neurodegenerative diseases (NDs), but the biological relevance of a single redox change is often dependent on the redox couple involved and on its subcellular origin. The biosensors based on engineered fluorescent proteins (redox-sensitive GFP [roGFP]) offer a unique opportunity to monitor redox changes in both physiological and pathological contexts in living animals and plants. Here, we review the use of roGFPs to monitor oxidative stress in different three adult-onset NDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Despite the many differences spanning from incidence to onset, the hypotheses on biological processes underlying both sporadic and familiar ND forms in humans outline a model in which noncompeting mechanisms are likely to converge in various unsuccessful patterns to mediate the selective degeneration of a specific neuronal population. roGFPs, targeted to different cell compartments, are successfully used as specific markers of cell toxicity, induced by expression of causative genes linked to a determined ND. We also report the use of roGFP to monitor oxidative stress induced by the expression of the ALS-causative gene SOD1.

Synapses, networks, brain development – funding basic neuroscience research in Germany by the Schram Foundation

Neuroforum ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Dorothea Schulte ◽  
Christian Rosenmund ◽  
Eckart D. Gundelfinger
Keyword(s):  
Brain Function ◽  
Basic Research ◽  
Academic Level ◽  
Neuroscience Research ◽  
Scientific Exchange ◽  
Deep Conviction ◽  
The Many ◽  
The Individual ◽  
The Brain ◽  
Made In

AbstractResearch driven solely by curiosity and the desire to understand fundamental principles of brain function. The freedom to address important questions with bold, sometimes risky experiments. A platform for open scientific exchange and discussions at highest academic level to provide new impulses to the field. And a growing number of scientists who share the passion for neuroscience and who join forces to tackle some of the big mysteries that surround the brain. These visions together with the deep conviction that basic research is the fundament needed for any progress in applied science motivated Dr. Armin Schram to create the foundation that carries his name. They are also the ideals that the foundation still pursues, and to date, 26 research proposals designed by individual researchers or small teams have been, or are, supported in this spirit. Here, we introduce the reader to the individual scientists who were awarded grants by the Schram Foundation over the years, highlight some of the many discoveries made in the course of their studies and list some of the key publications that arose from this work.

Prevalence and geographic distribution of haemophilia in Costa Rica

2010 ◽  
Vol 30 (S 01) ◽  
pp. S28-S31 ◽  
Author(s):  
J. Arroyo ◽  
L. Salazar-Sánchez ◽  
G. Jiménez-Cruz ◽  
P. Chaverri ◽  
E. Arrieta-Bolaños ◽  
...  
Keyword(s):  
Costa Rica ◽  
Survival Rates ◽  
Coagulation Factors ◽  
Developed Countries ◽  
Health Centers ◽  
Distribution Analysis ◽  
Distribution Maps ◽  
Immunodeficiency Virus ◽  
The Many ◽  
Low Prevalence

SummaryHaemophilia is the most frequent hereditary haemorrhagic illness and it is due to the deficiency of coagulation factors VIII (haemophilia A, HA) or IX (haemophilia B, HB).The prevalence of this disease varies according to the country, those having better survival rates having also higher prevalences. Specifically in Costa Rica, there are around 130 HA and 30 HB families. This study reports the prevalence and a spatial distribution analysis of both types of the disease in this country. The prevalence of haemophilia in this country is 7 cases per 100 000 men, for HA it is 6 cases per 100 000 and for HB it is 1 case per 100 000 male inhabitants. The prevalence of this disease is low when compared with other populations. This low prevalence could be due to the many patients that have died because of infection with human immunodeficiency virus during the 1980s. The prevalence of haemophilia in Costa Rica is almost one half of that present in developed countries. Nevertheless, the ratio between HA and HB follows world tendency: 5 : 1. In this study, nationwide geographical distribution maps were drawn in order to visualize the origin of severe cases and how this influences the pattern of distribution for both types of haemophilia. By means of these maps, it was possible to state that there is no association between the sites of maximum prevalence of mutated alleles and ethnicity. With this study, haemophilia prevalence distribution maps can be used to improve efforts for the establishment of hemophilia clinics or specialized health centers in those areas which hold the highest prevalences in this country. Also, this knowledge can be applied to improve treatment skills and offer the possibility of developing focused genetic counseling for these populations.

Methyl jasmonate delays the latency to anoxic convulsions by normalizing the brain levels of oxidative stress biomarkers and serum corticosterone contents in mice with repeated anoxic stress

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Abayomi Ololade Adelaja ◽  
Oluwafemi Gabriel Oluwole ◽  
Oritoke Modupe. Aluko ◽  
Solomon Umukoro
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Methyl Jasmonate ◽  
Brain Injuries ◽  
Antioxidant Property ◽  
Oxidative Stress Biomarkers ◽  
Serum Corticosterone ◽  
Stress Agent ◽  
Cellular Antioxidants ◽  
The Brain

AbstractObjectivesRepeated exposure to anoxic stress damages the brain through cortisol-mediated increases in oxidative stress and cellular-antioxidants depletion. Thus, compounds with antioxidant property might confer protection against anoxic stress-induced brain injuries. In this study, we further examined the protective effect of methyl jasmonate (MJ), a potent anti-stress agent against anoxic stress-induced convulsions in mice.MethodsThirty-six male Swiss mice randomized into six groups (n=6) were given MJ (25, 50 and 100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.) 30 min before 15 min daily exposure to anoxic stress for 7 days. The latency(s) to anoxic convulsion was recorded on day 7. The blood glucose and serum corticosterone levels were measured afterwards. The brains were also processed for the determination of malondialdehyde, nitrite, and glutathione levels.ResultsMethyl jasmonate (MJ) delayed the latency to anoxic convulsion and reduced the blood glucose and serum corticosterone levels. The increased malondialdehyde and nitrite contents accompanied by decreased glutathione concentrations in mice with anoxic stress were significantly attenuated by MJ.ConclusionsThese findings further showed that MJ possesses anti-stress property via mechanisms relating to the reduction of serum contents of corticosterone and normalization of brain biomarker levels of oxidative stress in mice with anoxic stress.

scholarly journals Is There a Brain Microbiome?

2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Ground Truth ◽  
Healthy Human ◽  
Strong Motivation ◽  
The Many ◽  
The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals Dexamethasone increased the survival rate in Plasmodium berghei-infected mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danilo Reymão Moreira ◽  
Ana Carolina Musa Gonçalves Uberti ◽  
Antonio Rafael Quadros Gomes ◽  
Michelli Erica Souza Ferreira ◽  
Aline da Silva Barbosa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Plasmodium Berghei ◽  
Redox Status ◽  
No Synthase ◽  
Ischemia And Reperfusion ◽  
Inos Inhibition ◽  
The Brain ◽  
Plasmodial Infection ◽  
Stimulation Of

AbstractThe present study aimed to evaluate the effects of dexamethasone on the redox status, parasitemia evolution, and survival rate of Plasmodium berghei-infected mice. Two-hundred and twenty-five mice were infected with Plasmodium berghei and subjected to stimulation or inhibition of NO synthesis. The stimulation of NO synthesis was performed through the administration of L-arginine, while its inhibition was made by the administration of dexamethasone. Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase in the survival rate of P. berghei-infected mice, and the data suggested the participation of oxidative stress in the brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted the survival rate of almost 90% of the animals until the 15th day of infection, with possible direct interference of ischemia and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of brain iNOS by dexamethasone caused a decrease in parasitemia and increased the survival rate of infected animals, suggesting that NO synthesis may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.

scholarly journals Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia

2021 ◽  
Vol 22 (10) ◽  
pp. 5272
Author(s):  
Débora Coimbra-Costa ◽  
Fernando Garzón ◽  
Norma Alva ◽  
Tiago C. C. Pinto ◽  
Fernando Aguado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hypobaric Hypoxia ◽  
Hypoxic Preconditioning ◽  
Severe Hypoxia ◽  
Efficient Tool ◽  
Adult Rats ◽  
Therapeutic Benefits ◽  
Background Exposure ◽  
The Brain ◽  
Apoptotic Cascade

Background: Exposure to intermittent hypoxia has been demonstrated to be an efficient tool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits. We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid brain injury caused by exposure to acute severe hypoxia (ASH). Methods: biomarkers of oxidative damage, mitochondrial apoptosis, and transcriptional factors in response to hypoxia were assessed by Western blot and immunohistochemistry in brain tissue. Four groups of rats were used: (1) normoxic (NOR), (2) exposed to ASH (FiO2 7% for 6 h), (3) exposed to IHH for 3 h per day over 8 days at 460 mmHg, and (4) ASH preconditioned after IHH. Results: ASH animals underwent increased oxidative-stress-related parameters, an upregulation in apoptotic proteins and had astrocytes with phenotype forms compatible with severe diffuse reactive astrogliosis. These effects were attenuated and even prevented when the animals were preconditioned with IHH. These changes paralleled the inhibition of NF-κB expression and the increase of erythropoietin (EPO) levels in the brain. Conclusions: IHH exerted neuroprotection against ASH-induced oxidative injury by preventing oxidative stress and inhibiting the apoptotic cascade, which was associated with NF-κB downregulation and EPO upregulation.

scholarly journals High-fat diet-induced obesity and impairment of brain neurotransmitter pool

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Control Group ◽  
High Fat ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

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