scholarly journals The Alteration of Chloride Homeostasis/GABAergic Signaling in Brain Disorders: Could Oxidative Stress Play a Role?

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1316
Author(s):  
Provvidenza M. Abruzzo ◽  
Cristina Panisi ◽  
Marina Marini
Keyword(s):  
Oxidative Stress ◽  
Inhibitory Effect ◽  
Autism Spectrum ◽  
New Drugs ◽  
Excitatory Effect ◽  
Chloride Homeostasis ◽  
Neuronal Precursors ◽  
Mature Neurons ◽  
The Impact ◽  
Developmental Switch

In neuronal precursors and immature neurons, the depolarizing (excitatory) effect of γ-Aminobutyric acid (GABA) signaling is associated with elevated [Cl−]i; as brain cells mature, a developmental switch occurs, leading to the decrease of [Cl−]i and to the hyperpolarizing (inhibitory) effect of GABAergic signaling. [Cl−]i is controlled by two chloride co-transporters: NKCC1, which causes Cl− to accumulate into the cells, and KCC2, which extrudes it. The ontogenetic upregulation of the latter determines the above-outlined switch; however, many other factors contribute to the correct [Cl−]i in mature neurons. The dysregulation of chloride homeostasis is involved in seizure generation and has been associated with schizophrenia, Down’s Syndrome, Autism Spectrum Disorder, and other neurodevelopmental disorders. Recently, much effort has been put into developing new drugs intended to inhibit NKCC1 activity, while no attention has been paid to the origin of [Cl−]i dysregulation. Our study examines the pathophysiology of Cl− homeostasis and focuses on the impact of oxidative stress (OS) and inflammation on the activity of Cl− co-transporters, highlighting the relevance of OS in numerous brain abnormalities and diseases. This hypothesis supports the importance of primary prevention during pregnancy. It also integrates the therapeutic framework addressed to restore normal GABAergic signaling by counteracting the alteration in chloride homeostasis in central nervous system (CNS) cells, aiming at limiting the use of drugs that potentially pose a health risk.

scholarly journals Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hui Zhao ◽  
Qiqi Wang ◽  
Ting Yan ◽  
Yu Zhang ◽  
Hui-juan Xu ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Epidemiological Studies ◽  
Causal Link ◽  
Autism Spectrum ◽  
Apparent Difference ◽  
Expression Of Genes ◽  
Neuronal Precursors ◽  
Substantial Progress ◽  
Tentative Evidence ◽  
Mature Neurons

Abstract Despite the substantial progress made in identifying genetic defects in autism spectrum disorder (ASD), the etiology for majority of ASD individuals remains elusive. Maternal exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug during pregnancy in human, has long been considered a risk factor to contribute to ASD susceptibility in offspring from epidemiological studies in humans. The similar exposures in murine models have provided tentative evidence to support the finding from human epidemiology. However, the apparent difference between rodent and human poses a significant challenge to extrapolate the findings from rodent models to humans. Here we report for the first time the neurodevelopmental and behavioral outcomes of maternal VPA exposure in non-human primates. Monkey offspring from the early maternal VPA exposure have significantly reduced NeuN-positive mature neurons in prefrontal cortex (PFC) and cerebellum and the Ki67-positive proliferating neuronal precursors in the cerebellar external granular layer, but increased GFAP-positive astrocytes in PFC. Transcriptome analyses revealed that maternal VPA exposure disrupted the expression of genes associated with neurodevelopment in embryonic brain in offspring. VPA-exposed juvenile offspring have variable presentations of impaired social interaction, pronounced stereotypies, and more attention on nonsocial stimuli by eye tracking analysis. Our findings in non-human primates provide the best evidence so far to support causal link between maternal VPA exposure and neurodevelopmental defects and ASD susceptibility in humans.

scholarly journals An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Joice Nascimento Barboza ◽  
Carlos da Silva Maia Bezerra Filho ◽  
Renan Oliveira Silva ◽  
Jand Venes R. Medeiros ◽  
Damião Pergentino de Sousa
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Antioxidant Properties ◽  
Redox Status ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Inflammatory Processes ◽  
Anti Inflammatory

The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.

scholarly journals Potential Novel Therapies for Neurodevelopmental Diseases Targeting Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Alexandrina S. Curpan ◽  
Alina-Costina Luca ◽  
Alin Ciobica
Keyword(s):  
Oxidative Stress ◽  
Neurodevelopmental Disorders ◽  
Antioxidant Properties ◽  
Autism Spectrum ◽  
Oxidative Status ◽  
Glutathione Level ◽  
Aspartate Receptor ◽  
Spectrum Disorders ◽  
The Impact ◽  
The Brain

Neurodevelopmental disorders are a category of diseases that is not yet fully understood. Due to their common traits and pathways, often it is difficult to differentiate between them based on their symptoms only. A series of hypotheses are trying to define their etiology, such as neuroinflammation, neurodegeneration, and immunology, but none have managed to explain their multifactorial manifestation. One feature that may link all theories is that of oxidative stress, with a redox imbalance as well as several other markers of oxidative damage (on lipids, proteins, and nucleic acids) being observed in both postmortem samples of the brain of patients with schizophrenia and autism spectrum disorders. However, the implication of oxidative stress in pathology is still distrustfully looked upon. For this purpose, in the current paper, we were interested in reviewing the implications of oxidative stress in these disorders as well as the impact of N-acetylcysteine on the oxidative status with a focus on the glutathione level and N-methyl-D-aspartate receptor. We were also interested in finding papers targeting the use of antioxidant properties of different plant extracts.

scholarly journals A Short S-Equol Exposure Has a Long-Term Inhibitory Effect on Adipogenesis in Mouse 3T3-L1 Cells

2021 ◽  
Vol 11 (20) ◽  
pp. 9657
Author(s):  
Gilberto Mandujano-Lázaro ◽  
Carlos Galaviz-Hernández ◽  
César A. Reyes-López ◽  
Julio C. Almanza-Pérez ◽  
Abraham Giacoman-Martínez ◽  
...  
Keyword(s):  
Weight Control ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Metabolic Effects ◽  
In Vitro Assays ◽  
Differentiation Protocol ◽  
Body Weight Control ◽  
The Impact

In the search for new drugs against obesity, the chronic disease that threatens human health worldwide, several works have focused on the study of estrogen homologs because of the role of estrogen receptors (ERs) in adipocyte growth. The isoflavone equol, an ERβ agonist, has shown beneficial metabolic effects in in vivo and in vitro assays; however, additional studies are required to better characterize its potential for body weight control. Here, we showed that the treatment of 3T3-L1 cells with 10 μM of S-equol for the first three days of the adipocyte differentiation protocol was able to prevent cells becoming semi-rounded and having a lipid droplet formation until the seventh day of culture; moreover, lipid accumulation was reduced by about 50%. Congruently, S-equol induced a reduction in mRNA expression of the adipogenic markers C/EBPα and PPARγ, and adipokines secretion, mainly Adiponectin, Leptin, Resistin, and MCP-1, while the release of PAI-1 was augmented. Moreover, it also reduced the expression of ERα and attenuated the subexpression of ERβ associated with adipogenesis. Altogether, our data suggested that S-equol binding to ERβ affects the transcriptional program that regulates adipogenesis and alters adipocyte functions. Future efforts will focus on studying the impact of S-equol on ER signaling pathways.

scholarly journals Effects of Supplementation With Antioxidant Agents on Sleep in Autism Spectrum Disorder: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Zambrelli ◽  
Althea Lividini ◽  
Sofia Spadavecchia ◽  
Katherine Turner ◽  
Maria Paola Canevini
Keyword(s):  
Oxidative Stress ◽  
Autism Spectrum Disorder ◽  
Sleep Disturbances ◽  
Sleep Problems ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Antioxidant Agents ◽  
High Prevalence ◽  
Severity Of The Disease ◽  
The Impact

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition, whose etiology remains poorly understood in most cases. Several genetic, epigenetic and environmental factors have been implicated in ASD pathogenesis and numerous studies have provided evidences for increased levels of oxidative stress and reduced antioxidant capacity in patients with ASD. Recent clinical trials explored supplementation with antioxidant agents as a potential therapeutic strategy for ASD, investigating the impact of this treatment on behavioral symptoms and on most common comorbidities of the disease, including sleep disturbances. Among all medical conditions associated to ASD, sleep problems are highly prevalent and are supposed to be positively related to the severity of the disease. Moreover, studies on animal models support the hypothesis of a relationship between oxidative stress and sleep deprivation. The aim of this review is to summarize the current state of the literature on the effect of antioxidant treatment on sleep disturbances in patients with ASD. Twenty-one articles were included in final synthesis. Of them, 15 studies involved Melatonin, 1 Tryptophan and 5 focused on supplementation with other antioxidant agents (namely Coenzyme Q10, L-Carnosine, Luteolin and Quercetin). Despite the high prevalence of comorbid sleep troubles in ASD, there is a paucity of data on the efficacy of antioxidant agents in those patients. Further research is needed to better define the role of antioxidants agents as adjunctive therapy in the management sleep disorders in children and adolescents affected with ASD.

scholarly journals Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on?

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Davide Pozzi ◽  
Marco Rasile ◽  
Irene Corradini ◽  
Michela Matteoli
Keyword(s):  
Inflammatory Cytokines ◽  
Developmental Disorders ◽  
Maternal Separation ◽  
Autism Spectrum ◽  
Main Determinant ◽  
Dynamic Tuning ◽  
Environmental Perturbations ◽  
Chloride Homeostasis ◽  
Expression Of Genes ◽  
Developmental Switch

Abstract Chloride homeostasis, the main determinant factor for the dynamic tuning of GABAergic inhibition during development, has emerged as a key element altered in a wide variety of brain disorders. Accordingly, developmental disorders such as schizophrenia, Autism Spectrum Disorder, Down syndrome, epilepsy, and tuberous sclerosis complex (TSC) have been associated with alterations in the expression of genes codifying for either of the two cotransporters involved in the excitatory-to-inhibitory GABA switch, KCC2 and NKCC1. These alterations can result from environmental insults, including prenatal stress and maternal separation which share, as common molecular denominator, the elevation of pro-inflammatory cytokines. In this review we report and systemize recent research articles indicating that different perinatal environmental perturbations affect the expression of chloride transporters, delaying the developmental switch of GABA signaling, and that inflammatory cytokines, in particular interleukin 1β, may represent a key causal factor for this phenomenon. Based on literature data, we provide therefore a unifying conceptual framework, linking environmental hits with the excitatory-to-inhibitory GABA switch in the context of brain developmental disorders.

scholarly journals Antioxidants in Kidney Diseases: The Impact of Bardoxolone Methyl

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jorge Rojas-Rivera ◽  
Alberto Ortiz ◽  
Jesus Egido
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
End Stage Renal Disease ◽  
Renal Damage ◽  
Kidney Diseases ◽  
New Drugs ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

Drugs targeting the renin-angiotensin-aldosterone system (RAAS) are the mainstay of therapy to retard the progression of proteinuric chronic kidney disease (CKD) such as diabetic nephropathy. However, diabetic nephropathy is still the first cause of end-stage renal disease. New drugs targeted to the pathogenesis and mechanisms of progression of these diseases beyond RAAS inhibition are needed. There is solid experimental evidence of a key role of oxidative stress and its interrelation with inflammation on renal damage. However, randomized and well-powered trials on these agents in CKD are scarce. We now review the biological bases of oxidative stress and its role in kidney diseases, with focus on diabetic nephropathy, as well as the role of the Keap1-Nrf2 pathway and recent clinical trials targeting this pathway with bardoxolone methyl.

Aviation and the Microbiome

2020 ◽  
Vol 91 (8) ◽  
pp. 651-661
Author(s):  
Joshua T. Davis ◽  
Hilary A. Uyhelji
Keyword(s):  
Psychological Health ◽  
Aviation Safety ◽  
Autism Spectrum ◽  
Unintended Consequences ◽  
Microbial Colonization ◽  
Future Research ◽  
Aerospace Medicine ◽  
Medical Certification ◽  
Physical Disorders ◽  
The Impact

INTRODUCTION: Although the impact of microorganisms on their hosts has been investigated for decades, recent technological advances have permitted high-throughput studies of the collective microbial genomes colonizing a host or habitat, also known as the microbiome. This literature review presents an overview of microbiome research, with an emphasis on topics that have the potential for future applications to aviation safety. In humans, research is beginning to suggest relationships of the microbiome with physical disorders, including type 1 and type 2 diabetes mellitus, cardiovascular disease, and respiratory disease. The microbiome also has been associated with psychological health, including depression, anxiety, and the social complications that arise in autism spectrum disorders. Pharmaceuticals can alter microbiome diversity, and may lead to unintended consequences both short and long-term. As research strengthens understanding of the connections between the microbiota and human health, several potential applications for aerospace medicine and aviation safety emerge. For example, information derived from tests of the microbiota has potential future relevance for medical certification of pilots, accident investigation, and evaluation of fitness for duty in aerospace operations. Moreover, air travel may impact the microbiome of passengers and crew, including potential impacts on the spread of disease nationally and internationally. Construction, maintenance, and cleaning regimens that consider the potential for microbial colonization in airports and cabin environments may promote the health of travelers. Altogether, the mounting knowledge of microbiome effects on health presents several opportunities for future research into how and whether microbiome-based insights could be used to improve aviation safety.Davis JT, Uyhelji HA. Aviation and the microbiome. Aerosp Med Hum Perform. 2020; 91(8):651–661.

Assessment of Superoxide Dismutase and Catalase Evolution in Different Stages of an Experimental Endometriosis

2017 ◽  
Vol 68 (6) ◽  
pp. 1381-1383
Author(s):  
Allia Sindilar ◽  
Carmen Lacramioara Zamfir ◽  
Eusebiu Viorel Sindilar ◽  
Alin Constantin Pinzariu ◽  
Eduard Crauciuc ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Reproductive Function ◽  
Female Rats ◽  
Oxygen Species ◽  
Efficient Treatment ◽  
Endometrial Cells ◽  
Gynecological Disorder ◽  
The Impact

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.

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