scholarly journals Shielding Effect of Ryanodine Receptor Modulator in Rat Model of Autism

2021 ◽  
pp. 1-36
Author(s):  
Hariom Kumar ◽  
◽  
G.T Kulkarni ◽  
Vishal Diwan ◽  
Bhupesh Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Social Behavior ◽  
Receptor Antagonist ◽  
Propionic Acid ◽  
Ryanodine Receptor ◽  
Repetitive Behavior ◽  
Ruthenium Red ◽  
Social Impairment ◽  
Shielding Effect ◽  
Co Morbidity

Introduction: A neurodevelopmental disorder, autism typically identified with three primary behavioral consequences, such as social impairment, communication problems and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid formed biologically by gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms. Methods: To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg / po on the 21st, 22nd, and 23rd postnatal days). Rats were also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on the propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood brain barrier permeability. Results: Ruthenium red was found to counter the propionic acid induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels. Conclusion: Ryanodine receptor antagonist presented neuroprotective effect in propionic acid induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition.

Smartphone sensing of social interactions in people with and without schizophrenia

2020 ◽  
Author(s):  
Daniel Fulford ◽  
Jasmine Mote ◽  
Rachel Gonzalez ◽  
Samuel Abplanalp ◽  
Yuting Zhang ◽  
...  
Keyword(s):  
Social Behavior ◽  
Social Functioning ◽  
Social Activity ◽  
Network Size ◽  
Social Impairment ◽  
Schizophrenia Spectrum Disorders ◽  
Social Network Size ◽  
Digital Phenotyping ◽  
Ecological Momentary

Social impairment is a cardinal feature of schizophrenia spectrum disorders (SZ). Smaller social network size, diminished social skills, and loneliness are highly prevalent. Existing, gold-standard assessments of social impairment in SZ often rely on self-reported information that depends on retrospective recall and detailed accounts of complex social behaviors. This is particularly problematic in people with SZ given characteristic cognitive impairments and reduced insight. Ecological Momentary Assessment (EMA; repeated self-reports completed in the context of daily life) allows for the measurement of social behavior as it occurs in vivo, yet still relies on participant input. Momentary characterization of behavior using smartphone sensors (e.g., GPS, microphone) may also provide ecologically valid indicators of social functioning. In the current study we tested associations between both active (e.g., EMA-reported number of interactions) and passive (GPS-based mobility, conversations captured by microphone) smartphone-based measures of social activity and measures of social functioning and loneliness to examine the promise of such measures for understanding social impairment in SZ. Our results indicate that passive markers of mobility were more consistently associated with EMA measures of social behavior in controls than in people with SZ. Furthermore, dispositional loneliness showed associations with mobility metrics in both groups, while general social functioning was less related to these metrics. Finally, interactions detected in the ambient audio were more tied to social functioning in SZ than in controls. Findings speak to the promise of smartphone-based digital phenotyping as an approach to understanding objective markers of social activity in people with and without schizophrenia.

Interleukin-1 Receptor Antagonist Decreases Hypothalamic Oxidative Stress During Experimental Sepsis

2015 ◽  
Vol 53 (6) ◽  
pp. 3992-3998 ◽  
Author(s):  
Fazal Wahab ◽  
Nilton N. Santos-Junior ◽  
Rodrigo Pereira de Almeida Rodrigues ◽  
Luis Henrique A. Costa ◽  
Carlos Henrique R. Catalão ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Experimental Sepsis ◽  
Interleukin 1 Receptor Antagonist

Characterization of the ryanodine receptor/channel of invertebrate muscle

1998 ◽  
Vol 274 (2) ◽  
pp. R494-R502 ◽  
Author(s):  
Kerry E. Quinn ◽  
Loriana Castellani ◽  
Karol Ondrias ◽  
Barbara E. Ehrlich
Keyword(s):  
Ryanodine Receptor ◽  
Single Channel ◽  
Microscopic Analysis ◽  
Ruthenium Red ◽  
Electron Microscopic ◽  
Release Channel ◽  
Single Channel Currents ◽  
Channel Currents ◽  
Bell Shaped Curve

Electron-microscopic analysis was used to show that invertebrate muscle has feetlike structures on the sarcoplasmic reticulum (SR) displaying the typical four-subunit appearance of the calcium (Ca2+) release channel/ryanodine receptor (RyR) observed in vertebrate skeletal muscle (K. E. Loesser, L. Castellani, and C. Franzini-Armstrong. J. Muscle Res. Cell Motil. 13: 161–173, 1992). SR vesicles from invertebrate muscle exhibited specific ryanodine binding and single channel currents that were activated by Ca2+, caffeine, and ATP and inhibited by ruthenium red. The single channel conductance of this invertebrate RyR was lower than that of the vertebrate RyR (49 and 102 pS, respectively). Activation of lobster and scallop SR Ca2+ release channel, in response to cytoplasmic Ca2+ (1 nM–10 mM), reflected a bell-shaped curve, as is found with the mammalian RyR. In contrast to a previous report (J.-H. Seok, L. Xu, N. R. Kramarcy, R. Sealock, and G. Meissner. J. Biol. Chem. 267: 15893–15901, 1992), our results show that regulation of the invertebrate and vertebrate RyRs is quite similar and suggest remarkably similar paths in these diverse organisms.

Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity

2019 ◽  
Vol 39 (1) ◽  
pp. 77-85 ◽  
Author(s):  
AA Fouad ◽  
HM Hafez ◽  
AAH Hamouda
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nuclear Factor Κb ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Stat3 Pathway ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Methotrexate (MTX) is a commonly used anticancer and immunosuppressive agent. However, MTX can induce hepatotoxicity due to oxidative stress, inflammation, and apoptosis. Hydrogen sulfide (H2S), the endogenous gaseous molecule, has antioxidant, anti-inflammatory, and anti-apoptotic effects. The present work explored the probable protective effect of H2S against MTX hepatotoxicity in rats and also the possible mechanisms underlying this effect. MTX was given at a single intraperitoneal (i.p.) dose of 20 mg/kg. Sodium H2S (56 µmol /kg/day, i.p.), as H2S donor, was given for 10 days, starting 6 days before MTX administration. H2S significantly reduced serum alanine aminotransferase, hepatic malondialdehyde, interleukin 6, nuclear factor κB p65, cytosolic cytochrome c, phosphorylated signal transducer and activator of transcription 3, and Bax/Bcl-2 ratio and significantly increased hepatic total antioxidant capacity and endothelial nitric oxide synthase (eNOS) in rats received MTX. In addition, H2S minimized the histopathological injury and significantly decreased the expression of STAT3 in liver tissue of MTX-challenged rats. The effects of H2S were significantly antagonized by administration of glibenclamide as KATP channel blocker, Nω-nitro-l-arginine, as eNOS inhibitor, or ruthenium red, as transient receptor potential vanilloid 1 (TRPV1) antagonist. It was concluded that H2S provided significant hepatoprotection in MTX-challenged rats through its antioxidant, anti-inflammatory, anti-apoptotic effects. These effects are most probably mediated by the ability of H2S to act as IL-6/STAT3 pathway modulator, KATP channel opener, eNOS activator, and TRPV1 agonist.

scholarly journals Role of NAD+, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders

2013 ◽  
Vol 6s1 ◽  
pp. IJTR.S11355 ◽  
Author(s):  
Musthafa Mohamed Essa ◽  
Selvaraju Subash ◽  
Nady Braidy ◽  
Samir Al-Adawi ◽  
Chai K Lim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Antioxidant Defense ◽  
Developmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Tryptophan Metabolism ◽  
Spectrum Disorders ◽  
Impaired Energy Metabolism

Autism spectrum disorder (ASD) is a pervasive neuro-developmental disorder characterized by impaired social interaction, reduced/absent verbal and non-verbal communication, and repetitive behavior during early childhood. The etiology of this developmental disorder is poorly understood, and no biomarkers have been identified. Identification of novel biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. Studies suggest that oxidative stress-induced mechanisms and reduced antioxidant defense, mitochondrial dysfunction, and impaired energy metabolism (NAD+, NADH, ATP, pyruvate, and lactate), are major causes of ASD. This review provides renewed insight regarding current autism research related to oxidative stress, mitochondrial dysfunction, and altered tryptophan metabolism in ASD.

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