Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Thus, since the molecular mechanisms underlying tolerance to amphetamine are still unknown, an animal model to identify the neurochemical mechanisms associated with drug tolerance is greatly needed. Here we took advantage of a unique behavior caused by amphetamine in <i>Caenorhabditis elegans</i> to investigate whether this simple, but powerful, genetic model develops tolerance following repeated exposure to amphetamine. We found that at least 3 treatments with 0.5 mM amphetamine were necessary to see a reduction in the amphetamine-induced behavior and, thus, to promote tolerance. Moreover, we found that, after intervals of 60/90 minutes between treatments, animals were more likely to exhibit tolerance than animals that underwent 10-minute intervals between treatments. Taken together, our results show that <i>C. elegans</i> is a suitable system to study tolerance to drugs of abuse such as amphetamines.

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Edible Flowers of Tagetes erecta L. as Functional Ingredients: Phenolic Composition, Antioxidant and Protective Effects on Caenorhabditis elegans

Nutrients ◽

10.3390/nu10122002 ◽

2018 ◽

Vol 10 (12) ◽

pp. 2002 ◽

Cited By ~ 7

Author(s):

Cristina Moliner ◽

Lillian Barros ◽

Maria Dias ◽

Víctor López ◽

Elisa Langa ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

In Vivo Model ◽

Tagetes Erecta ◽

Protective Effects ◽

Phenolic Composition ◽

C Elegans ◽

Amyloid Toxicity ◽

Phenolic Profiles ◽

Tagetes Erecta L

Tagetes erecta L. has long been consumed for culinary and medicinal purposes in different countries. The aim of this study was to explore the potential benefits from two cultivars of T. erecta related to its polyphenolic profile as well as antioxidant and anti-aging properties. The phenolic composition was analyzed by LC-DAD-ESI/MSn. Folin-Ciocalteu, DPPH·, and FRAP assays were performed in order to evaluate reducing antiradical properties. The neuroprotective potential was evaluated using the enzymes acetylcholinesterase and monoamine oxidase. Caenorhabditis elegans was used as an in vivo model to assess extract toxicity, antioxidant activity, delayed aging, and reduced β-amyloid toxicity. Both extracts showed similar phenolic profiles and bioactivities. The main polyphenols found were laricitin and its glycosides. No acute toxicity was detected for extracts in the C. elegans model. T. erecta flower extracts showed promising antioxidant and neuroprotective properties in the different tested models. Hence, these results may add some information supporting the possibilities of using these plants as functional foods and/or as nutraceutical ingredients.

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Identification of gmhA, a Yersinia pestis Gene Required for Flea Blockage, by Using a Caenorhabditis elegans Biofilm System

Infection and Immunity ◽

10.1128/iai.73.11.7236-7242.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7236-7242 ◽

Cited By ~ 55

Author(s):

Creg Darby ◽

Sandya L. Ananth ◽

Li Tan ◽

B. Joseph Hinnebusch

Keyword(s):

Caenorhabditis Elegans ◽

Yersinia Pestis ◽

Biofilm Formation ◽

Yersinia Pseudotuberculosis ◽

C Elegans ◽

Transposon Insertion ◽

Insertion Mutants ◽

Random Screening

ABSTRACT Yersinia pestis, the cause of bubonic plague, blocks feeding by its vector, the flea. Recent evidence indicates that blockage is mediated by an in vivo biofilm. Y. pestis and the closely related Yersinia pseudotuberculosis also make biofilms on the cuticle of the nematode Caenorhabditis elegans, which block this laboratory animal's feeding. Random screening of Y. pseudotuberculosis transposon insertion mutants with a C. elegans biofilm assay identified gmhA as a gene required for normal biofilms. gmhA encodes phosphoheptose isomerase, an enzyme required for synthesis of heptose, a conserved component of lipopolysaccharide and lipooligosaccharide. A Y. pestis gmhA mutant was constructed and was severely defective for C. elegans biofilm formation and for flea blockage but only moderately defective in an in vitro biofilm assay. These results validate use of the C. elegans biofilm system to identify genes and pathways involved in Y. pestis flea blockage.

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Rosemary Flowers as Edible Plant Foods: Phenolic Composition and Antioxidant Properties in Caenorhabditis elegans

Antioxidants ◽

10.3390/antiox9090811 ◽

2020 ◽

Vol 9 (9) ◽

pp. 811

Author(s):

Cristina Moliner ◽

Víctor López ◽

Lillian Barros ◽

Maria Inês Dias ◽

Isabel C. F. R. Ferreira ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Antioxidant Properties ◽

Ethanolic Extract ◽

Food Ingredient ◽

Edible Plant ◽

Phenolic Profile ◽

C Elegans ◽

Rosmarinus Officinalis L

Rosmarinus officinalis L., commonly known as rosemary, has been largely studied for its wide use as food ingredient and medicinal plant; less attention has been given to its edible flowers, being necessary to evaluate their potential as functional foods or nutraceuticals. To achieve that, the phenolic profile of the ethanolic extract of R. officinalis flowers was determined using LC-DAD-ESI/MSn and then its antioxidant and anti-ageing potential was studied through in vitro and in vivo assays using Caenorhabditis elegans. The phenolic content was 14.3 ± 0.1 mg/g extract, trans rosmarinic acid being the predominant compound in the extract, which also exhibited a strong antioxidant capacity in vitro and increased the survival rate of C. elegans exposed to lethal oxidative stress. Moreover, R. officinalis flowers extended C. elegans lifespan up to 18%. Therefore, these findings support the potential use of R. officinalis flowers as ingredients to develop products with pharmaceutical and/or nutraceutical potential.

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Hepatobiliary Differentiation: Principles from Embryonic Liver Development

Seminars in Liver Disease ◽

10.1055/s-0040-1709679 ◽

2020 ◽

Vol 40 (04) ◽

pp. 365-372

Author(s):

Scott H. Freeburg ◽

Wolfram Goessling

Keyword(s):

Molecular Mechanisms ◽

Alagille Syndrome ◽

Cell Types ◽

Extrinsic Cues ◽

Hepatic Portal Vein ◽

Hepatic Portal ◽

Transcription Factor Expression ◽

In Vitro Data

AbstractHepatocytes and biliary epithelial cells (BECs), the two endodermal cell types of the liver, originate from progenitor cells called hepatoblasts. Based principally on in vitro data, hepatoblasts are thought to be bipotent stem cells with the potential to produce both hepatocytes and BECs. However, robust in vivo evidence for this model has only recently emerged. We examine the molecular mechanisms that stimulate hepatoblast differentiation into hepatocytes or BECs. In the absence of extrinsic cues, the default fate of hepatoblasts is hepatocyte differentiation. Inductive cues from the hepatic portal vein, however, initiate transcription factor expression in hepatoblasts, driving biliary specification. Defining the mechanisms of hepatobiliary differentiation provides important insights into congenital disorders, such as Alagille syndrome, and may help to better characterize the poorly understood hepatic lineage relationships observed during regeneration from liver injury.

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The Foodborne Strain Lactobacillus fermentum MBC2 Triggers pept-1-Dependent Pro-Longevity Effects in Caenorhabditis elegans

Microorganisms ◽

10.3390/microorganisms7020045 ◽

2019 ◽

Vol 7 (2) ◽

pp. 45 ◽

Cited By ~ 15

Author(s):

Emily Schifano ◽

Paola Zinno ◽

Barbara Guantario ◽

Marianna Roselli ◽

Sante Marcoccia ◽

...

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Acid Tolerance ◽

Lactobacillus Fermentum ◽

In Vivo Model ◽

Aging Effects ◽

Pumping Rate ◽

Gut Colonization

Lactic acid bacteria (LAB) are involved in several food fermentations and many of them provide strain-specific health benefits. Herein, the probiotic potential of the foodborne strain Lactobacillus fermentum MBC2 was investigated through in vitro and in vivo approaches. Caenorhabditis elegans was used as an in vivo model to analyze pro-longevity and anti-aging effects. L. fermentum MBC2 showed a high gut colonization capability compared to E. coli OP50 (OP50) or L. rhamnosus GG (LGG). Moreover, analysis of pumping rate, lipofuscin accumulation, and body bending showed anti-aging effects in L. fermentum MBC2-fed worms. Studies on PEPT-1 mutants demonstrated that pept-1 gene was involved in the anti-aging processes mediated by this bacterial strain through DAF-16, whereas the oxidative stress protection was PEPT-1 independent. Moreover, analysis of acid tolerance, bile tolerance, and antibiotic susceptibility were evaluated. L. fermentum MBC2 exerted beneficial effects on nematode lifespan, influencing energy metabolism and oxidative stress resistance, resulted in being tolerant to acidic pH and able to adhere to Caco-2 cells. Overall, these findings provide new insight for application of this strain in the food industry as a newly isolated functional starter. Furthermore, these results will also shed light on C. elegans molecular players involved in host-microbe interactions.

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Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

Neurosurgical FOCUS ◽

10.3171/2014.9.focus14504 ◽

2014 ◽

Vol 37 (6) ◽

pp. E12 ◽

Cited By ~ 63

Author(s):

Encouse B. Golden ◽

Hee-Yeon Cho ◽

Ardeshir Jahanian ◽

Florence M. Hofman ◽

Stan G. Louie ◽

...

Keyword(s):

Molecular Mechanisms ◽

Malignant Gliomas ◽

Glioma Cells ◽

In Vivo Model ◽

Autophagosome Formation ◽

Individual Drug ◽

In Vivo Experiments ◽

Associated Proteins

Object In a recent clinical trial, patients with newly diagnosed glioblastoma multiforme benefited from chloroquine (CQ) in combination with conventional therapy (resection, temozolomide [TMZ], and radiation therapy). In the present study, the authors report the mechanism by which CQ enhances the therapeutic efficacy of TMZ to aid future studies aimed at improving this therapeutic regimen. Methods Using in vitro and in vivo experiments, the authors determined the mechanism by which CQ enhances TMZ cytotoxicity. They focused on the inhibition-of-autophagy mechanism of CQ by knockdown of the autophagy-associated proteins or treatment with autophagy inhibitors. This mechanism was tested using an in vivo model with subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ. Results Knockdown of the autophagy-associated proteins (GRP78 and Beclin) or treatment with the autophagy inhibitor, 3-methyl adenine (3-MA), blocked autophagosome formation and reduced CQ cytotoxicity, suggesting that autophagosome accumulation precedes CQ-induced cell death. In contrast, blocking autophagosome formation with knockdown of GRP78 or treatment with 3-MA enhanced TMZ cytotoxicity, suggesting that the autophagy pathway protects from TMZ-induced cytotoxicity. CQ in combination with TMZ significantly increased the amounts of LC3B-II (a marker for autophagosome levels), CHOP/GADD-153, and cleaved PARP (a marker for apoptosis) over those with untreated or individual drug-treated glioma cells. These molecular mechanisms seemed to take place in vivo as well. Subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ displayed higher levels of CHOP/GADD-153 than did untreated or individual drug-treated tumors. Conclusions Taken together, these results demonstrate that CQ blocks autophagy and triggers endoplasmic reticulum stress, thereby increasing the chemosensitivity of glioma cells to TMZ.

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Mulberry Anthocyanin Extract Ameliorates Oxidative Damage in HepG2 Cells and Prolongs the Lifespan of Caenorhabditis elegans through MAPK and Nrf2 Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7956158 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 19

Author(s):

Fujie Yan ◽

Yushu Chen ◽

Ramila Azat ◽

Xiaodong Zheng

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Hepg2 Cells ◽

Insulin Signalling ◽

Glucose Consumption ◽

Redox Status ◽

C Elegans ◽

Beneficial Effects

Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation. In vivo, extended lifespan was observed in C. elegans damaged by paraquat in the presence of MAE, while these beneficial effects were disappeared in pmk-1 and daf-16 mutants. PMK-1 and SKN-1 were activated after exposure to paraquat and MAE suppressed PMK-1 activation but enhanced SKN-1 stimulation. Our findings suggested that MAE recovered redox status in HepG2 cells and C. elegans that suffered from oxidative stress, which might be by targeting MAPKs and Nrf2.

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Identification of phenolic secondary metabolites from Schotia brachypetala Sond. (Fabaceae) and demonstration of their antioxidant activities in Caenorhabditis elegans

10.7287/peerj.preprints.1768v1 ◽

2016 ◽

Author(s):

Mansour Sobeh ◽

Esraa A ElHawary ◽

Herbenya Peixoto ◽

Rola M Labib ◽

Heba Handoussa ◽

...

Keyword(s):

Antioxidant Activity ◽

Caenorhabditis Elegans ◽

Nuclear Translocation ◽

Antioxidant Activities ◽

In Vitro Assays ◽

Flavonoid Glycosides ◽

Alcoholic Extract ◽

C Elegans

Background: Schotia brachypetala Sond. (Fabaceae) is an endemic tree of Southern Africa whose phytochemistry and pharmacology were slightly studied.The present work aimed at profiling the major phenolics compounds present in the hydro-alcoholic extract from S. brachypetala leaves (SBE) using LC/HRESI/MS/MS and NMR and prove their antioxidant capabilities using novel methods. Methods: In vitro assays; DPPH, TEAC persulfate decolorizing kinetic and FRAP assays, and in vivo assays: Caenorhabditis elegans strains maintenance, Intracellular ROS in C. elegans, Survival assay, GFP expression and Subcellular DAF-16 localization were employed to evaluate the antioxidant activity. Results: More than forty polyphenols ,including flavonoid glycosides, galloylated flavonoid glycosides, isoflavones, dihydrochalcones, procyanidins, anthocyanins, hydroxybenzoic acid derivatives, hydrolysable tannins, and traces of methylated and acetylated flavonoid derivatives were identified. Three compounds were isolated and identified from the genus Schotia for the first time, namely gallic acid, myricetin-3-O-α-L-1C4-rhamnoside and quercetin-3-O-L-1C4-rhamnoside.The tested extract was able to protect the worms against juglone induced oxidative stress and attenuate the reactive oxygen species (ROS) accumulation. SBE was also able to attenuate the levels of heat shock protein (HSP) expression. Discussion: A pronounced antioxidant activity in vivo, which can be attributed to its ability to promote the nuclear translocation of DAF-16/FOXO, the main transcription factor regulating the expression of stress response genes. The remarkable antioxidant activity in vitro and in vivo correlates to SBE rich phenolic profile.

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Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

Frontiers in Nutrition ◽

10.3389/fnut.2020.00135 ◽

2020 ◽

Vol 7 ◽

Author(s):

Cyril Poupet ◽

Christophe Chassard ◽

Adrien Nivoliez ◽

Stéphanie Bornes

Keyword(s):

Caenorhabditis Elegans ◽

High Throughput Screening ◽

Large Scale ◽

Molecular Mechanisms ◽

Probiotic Properties ◽

C Elegans ◽

Probiotic Potential ◽

Challenges And Opportunities ◽

Future Challenges

Caenorhabditis elegans, a non-parasitic nematode emerges as a relevant and powerful candidate as an in vivo model for microorganisms-microorganisms and microorganisms-host interactions studies. Experiments have demonstrated the probiotic potential of bacteria since they can provide to the worm a longer lifespan, an increased resistance to pathogens and to oxidative or heat stresses. Probiotics are used to prevent or treat microbiota dysbiosis and associated pathologies but the molecular mechanisms underlying their capacities are still unknown. Beyond safety and healthy aspects of probiotics, C. elegans represents a powerful way to design large-scale studies to explore transkingdom interactions and to solve questioning about the molecular aspect of these interactions. Future challenges and opportunities would be to validate C. elegans as an in vivo tool for high-throughput screening of microorganisms for their potential probiotic use on human health and to enlarge the panels of microorganisms studied as well as the human diseases investigated.

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Polyphenols from Blumea laciniata Extended the Lifespan and Enhanced Resistance to Stress in Caenorhabditis elegans via the Insulin Signaling Pathway

Antioxidants ◽

10.3390/antiox10111744 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1744

Author(s):

Tao Chen ◽

Siyuan Luo ◽

Xiaoju Wang ◽

Yiling Zhou ◽

Yali Dai ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Signaling Pathway ◽

Relevant Literature ◽

Folk Medicine ◽

Ageing Effect ◽

C Elegans ◽

Enhanced Resistance ◽

Resistance To Stress

Blumea laciniata is widely used as a folk medicine in Asia, but relevant literature on it is rarely reported. We confirmed that polyphenol extract (containing chlorogenic acid, rutin, and luteolin-4-O-glucoside) from B. laciniata (EBL) showed strong antioxidant ability in vitro. Hence, in this work, we applied Caenorhabditis elegans to further investigate the antioxidant and anti-ageing abilities of EBL in vivo. The results showed that EBL enhanced the survival of C. elegans under thermal stress by 12.62% and sharply reduced the reactive oxygen species level as well as the content of malonaldehyde. Moreover, EBL increased the activities of antioxidant enzymes such as catalase and superoxide dismutase. Additionally, EBL promoted DAF-16, a transcription factor, into the nucleus. Besides, EBL extended the lifespan of C. elegans by 17.39%, showing an anti-ageing effect. Different mutants indicated that the insulin/IGF-1 signaling pathway participated in the antioxidant and anti-ageing effect of EBL on C. elegans.

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