scholarly journals Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1285
Author(s):  
Seong Soon Kim ◽  
Hyemin Kan ◽  
Kyu-Seok Hwang ◽  
Jung Yoon Yang ◽  
Yuji Son ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epileptic Seizure ◽  
Neurological Disorders ◽  
Aminobutyric Acid ◽  
Oxygen Species ◽  
Gamma Aminobutyric Acid ◽  
Zebrafish Model ◽  
Neuroprotective Effects ◽  
Drug Discovery And Development ◽  
Spontaneous Seizures

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.

scholarly journals Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Akt Signaling ◽  
Atp Depletion ◽  
Oxygen Species ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects ◽  
Lpa1 Receptor

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

Pharmacotherapeutic Potential of Garlic in Age-Related Neurological Disorders

2021 ◽  
Vol 20 ◽  
Author(s):  
Ramin Ahangar-Sirous ◽  
Mohadeseh Poudineh ◽  
Arina Ansari ◽  
Ali Nili ◽  
Seyyed Mohammad Matin Alavi Dana ◽  
...  
Keyword(s):  
Public Health ◽  
Oxidative Stress ◽  
Neurological Disorders ◽  
Allium Sativum ◽  
Aged Garlic Extract ◽  
Neuroprotective Effects ◽  
Age Related ◽  
Pathologic Features ◽  
The Common ◽  
Aged Garlic

: Age-related neurological disorders [ANDs] involve neurodegenerative diseases [NDDs] such as Alzheimer's disease [AD], the most frequent kind of dementia in elderly people, and Parkinson's disease [PD], and also other disorders like epilepsy and migraine. Although ANDs are multifactorial, Aging is a principal risk factor for them. The common and most main pathologic features among ANDs are inflammation, oxidative stress, and misfolded proteins accumulation. Since failing brains caused by ANDs impose a notable burden on public health and their incidence is increasing, a lot of works has been done to overcome them. Garlic, Allium sativum, has been used for different medical purposes globally and more than thousands of publications have reported its health benefits. Garlic and aged garlic extract are considered potent anti-inflammatory and antioxidants agents and can have remarkable neuroprotective effects. This review is aimed to summarize knowledge on the pharmacotherapeutic potential of garlic and its components in ANDs.

scholarly journals The Neuroprotective Effects of Astaxanthin: Therapeutic Targets and Clinical Perspective

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2640 ◽  
Author(s):  
Fakhri ◽  
Aneva ◽  
Farzaei ◽  
Sobarzo-Sánchez
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Spinal Cord Injuries ◽  
Neurological Diseases ◽  
Mechanisms Of Action ◽  
Clinical Perspective ◽  
Neuroprotective Effects ◽  
Brain And Spinal Cord ◽  
Neuronal Disorders

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also considered.

scholarly journals Abnormal expression of GABAA receptor sub-units and hypomotility upon loss of gabra1 in zebrafish

2020 ◽  
Author(s):  
Nayeli Reyes-Nava ◽  
Hung-Chun Yu ◽  
Curtis R. Coughlin ◽  
Tamim H. Shaikh ◽  
Anita M. Quintana
Keyword(s):  
Nervous System ◽  
De Novo ◽  
Functional Approach ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Behavioral Deficits ◽  
Whole Exome ◽  
System Disorder

ABSTRACTWe used whole exome sequencing (WES) to determine the genetic etiology of a patient with a multi-system disorder characterized by a seizure phenotype. WES identified a heterozygous de novo missense mutation in the GABRA1 gene (c.875C>T). GABRA1 encodes the alpha subunit of the Gamma-Aminobutyric Acid receptor A (GABAAR). The GABAAR is a ligand gated ion channel that mediates the fast inhibitory signals of the nervous system and mutations in the sub-units that compose the GABAAR have been previously associated with human disease. To understand the mechanisms by which GABRA1 regulates brain development, we developed a zebrafish model of gabra1 deficiency. gabra1 expression is restricted to the nervous system and behavioral analysis of morpholino injected larvae suggests that the knockdown of gabra1 results in hypoactivity and defects in the expression of other sub-units of the GABAAR. Expression the human GABRA1 protein in morphants partially restored the hypomotility phenotype. In contrast, the expression of the c.875C>T variant did not restore these behavioral deficits. Collectively, these results represent a functional approach to understand the mechanisms by which loss of function alleles cause disease.

scholarly journals Administration of Quercetin Ameliorates Lipopolysaccharide Induced Neuroinflammation and Oxidative Stress in Adult Zebrafish

2021 ◽  
Author(s):  
Sukhdev Singh ◽  
Kuleshwar Sahu ◽  
Lakshay Kapil ◽  
Charan Singh ◽  
Arti Singh
Keyword(s):  
Oxidative Stress ◽  
Neurological Disorders ◽  
Treated Group ◽  
Post Treatment ◽  
Test Time ◽  
Adult Zebrafish ◽  
Neuroprotective Effects ◽  
Behavioral Abnormalities ◽  
Bottom Zone ◽  
Quercetin Treatment

Abstract Background: Quercetin is a natural flavonoid which is known to have numerous pharmacological activities such as antioxidative, anti-inflammatory and neuroprotective effects against various neurological disorders. Lipopolysaccharide (LPS) is a potent endotoxin, reported to cause various neurological disorders such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Stroke (Brain Attack), Meningitis. Aim: The present study was designed to investigate the possibility thatquercetin ameliorates LPS induced oxidative stress and neuroinflammation in adult zebrafish. Materials and methods: Zebrafish (weighing 470-530 mg) were treated with single injection of LPS (1 mg/kg) intraperitoneally (i.p.) followed by post treatment for 7 days with quercetin (50 and 100 mg/kg; i.p.). After sacrificed, brain was harvested and subjected for biochemical, molecular and histological analyses. Results: Results revealed post treatment with quercetin was able to ameliorate the behavioral abnormalities as in novel diving test- time spent in top zone (TSTZ), and number of entries in top zone was significantly more as compared to time spent in bottom zone (TSBZ). In light-dark chamber test- time spent in light zone (TSLZ), and number of entries in light zone was significantly more as compared to time spent in dark compartment (TSDC). Additionally, results of histopathology (H & E stain) studies showed less disruption in neuronal cells as compared to LPS treated group. Moreover, results of molecular analysis implies that quercetin treatment significantly decrease TNF-α and IL-1β level as compared to LPS treated animals. Further, results of biochemical analysis reveal that quercetin reduce the level of LPO, nitrite, AChEs and increases anti-oxidant GSH. Conclusion: Quercetin treatment helps to prevent oxidative damage and neuroinflammation in LPS treated adult zebrafish.

scholarly journals Biosensor Technology in Diagnostics and Mechanistic Studies of Epilepsy

Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 20
Author(s):  
Michael Thompson ◽  
Amanda J. Ackroyd
Keyword(s):  
Real Time ◽  
Epileptic Seizure ◽  
Neurological Disorders ◽  
Molecular Biomarkers ◽  
Aminobutyric Acid ◽  
Potassium Cation ◽  
Special Role ◽  
Mechanistic Studies ◽  
Considerable Potential ◽  
Fundamental Understanding

Epilepsy is represented by a set of neurological disorders that result in recurring seizures and convulsions. Although several types of the condition have been characterized, the underlying cause for these remains largely unknown. A number of molecular biomarkers for epilepsy have been identified including glutamate, γ-aminobutyric acid, and miRNAs. In addition, a special role appears to be played by the potassium cation. Detection of these species is anticipated to assist in both diagnosis and fundamental understanding of the condition. This review details the application of a number of biosensor devices that have been designed specifically for the detection of both molecular biomarkers and the K+ cation in proximity to an animal cortex. These devices offer considerable potential not only for diagnostic goals, but also for study of the cause and spread of the epileptic seizure, especially if such biosensors can detect analytes in a multiplexed, real-time manner.

scholarly journals Fisetin Rescues the Mice Brains Against D-Galactose-Induced Oxidative Stress, Neuroinflammation and Memory Impairment

2021 ◽  
Vol 12 ◽  
Author(s):  
Sareer Ahmad ◽  
Amjad Khan ◽  
Waqar Ali ◽  
Myeung Hoon Jo ◽  
Junsung Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurological Disorders ◽  
Memory Impairment ◽  
Neurological Impairment ◽  
Oxygen Species ◽  
Protective Effects ◽  
Age Related ◽  
Ros Accumulation ◽  
Anti Oxidant ◽  
Antioxidant Effects

Herein, we have evaluated the protective potentials of Fisetin against d-galactose-induced oxidative stress, neuroinflammation, and memory impairment in mice. d-galactose (D-gal) causes neurological impairment by inducing reactive oxygen species (ROS), neuroinflammation, and synaptic dysfunction, whereas fisetin (Fis) is a natural flavonoid having potential antioxidant effects, and has been used against different models of neurodegenerative diseases. Here, the normal mice were injected with D-gal (100 mg/kg/day for 60 days) and fisetin (20 mg/kg/day for 30 days). To elucidate the protective effects of fisetin against d-galactose induced oxidative stress-mediated neuroinflammation, we conducted western blotting, biochemical, behavioral, and immunofluorescence analyses. According to our findings, D-gal induced oxidative stress, neuroinflammation, synaptic dysfunctions, and cognitive impairment. Conversely, Fisetin prevented the D-gal-mediated ROS accumulation, by regulating the endogenous anti-oxidant mechanisms, such as Sirt1/Nrf2 signaling, suppressed the activated p-JNK/NF-kB pathway, and its downstream targets, such as inflammatory cytokines. Hence, our results together with the previous reports suggest that Fisetin may be beneficial in age-related neurological disorders.

Association of Oxidative Stress with Neurological Disorders

2021 ◽  
Vol 19 ◽  
Author(s):  
Waseem Hassan ◽  
Hamsa Noreen ◽  
Shakila Rehman ◽  
Mohammad Amjad Kamal ◽  
Joao Batista Teixeira da Rocha
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Biological Effects ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Neuronal Membranes

Background: Oxidative stress is one of the main contributing factors involved in cerebral biochemical impairment. The higher susceptibility of the central nervous system to reactive oxygen species mediated damage could be attributed to several factors. For example, neurons use a greater quantity of oxygen, many parts of the brain have higher concentraton of iron, and neuronal mitochondria produce huge content of hydrogen peroxide. In addition, neuronal membranes have polyunsaturated fatty acids, which are predominantly vulnerable to oxidative stress (OS). OS is the imbalance between reactive oxygen species generation and cellular antioxidant potential. This may lead to various pathological conditions and diseases, especially neurodegenerative diseases such as, Parkinson’s, Alzheimer’s, and Huntington’s diseases. Objectives: In this study, we explored the involvement of OS in neurodegenerative diseases. Methods: We used different search terms like “oxidative stress and neurological disorders” “free radicals and neurodegenerative disorders” “oxidative stress, free radicals, and neurological disorders” and “association of oxidative stress with the name of disorders taken from the list of neurological disorders. We tried to summarize the source, biological effects, and physiologic functions of ROS. Results: Finally, it was noted that more than 190 neurological disorders are associated with oxidative stress.

Effect of both selenium and biosynthesized nanoselenium particles on cadmium-induced neurotoxicity in albino rats

2019 ◽  
Vol 39 (2) ◽  
pp. 159-172 ◽  
Author(s):  
MA Al Kahtani
Keyword(s):  
Oxidative Stress ◽  
Amyloid Β ◽  
Aminobutyric Acid ◽  
Food Chains ◽  
Albino Rats ◽  
Gamma Aminobutyric Acid ◽  
Superoxide Dismutase Gene ◽  
Kidney Liver ◽  
The Brain ◽  
Very High

Because cadmium (Cd) is not naturally degradable by ecosystems, it interferes with many types of food chains. Cd accumulates in the kidney, liver and in the nervous tissues, especially the brain. The neurotoxicity of Cd is very high, as it alters the integrity, and increases the permeability, of the blood–brain barrier. Cd penetrates and accumulates in neurons in the brains of rats. This study reveals that Cd decreases antioxidant enzymes and increases oxidative stress in the brain. In addition, Cd increases lipid peroxidation of brain tissues. Cd increases the expression of the Cu/Zn superoxide dismutase gene. It also affects cholinergic, glutamatergic, gamma-Aminobutyric acid (GABAergic), dopamine, serotonin and acetylcholine neurotransmitters in brain tissue. Consequently, Cd increases the formation of amyloid β, a neurotoxic index, and induces apoptosis by changing the quality and the quantity of Bcl-2, Bax and p53 proteins. In conclusion, both selenium and nanoselenium show potential antioxidant activity and promote recovery from the neurotoxic action of Cd.

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