scholarly journals Perfluorooctane Sulfonate (PFOS) Produces Dopaminergic Neuropathology in Caenorhabditis elegans

2019 ◽  
Vol 172 (2) ◽  
pp. 417-434 ◽  
Author(s):  
Shreesh Raj Sammi ◽  
Rachel M Foguth ◽  
Claudia Sofía Nieves ◽  
Chloe De Perre ◽  
Peter Wipf ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Neurological Diseases ◽  
Cholinergic Neurons ◽  
Perfluorooctane Sulfonate ◽  
Adverse Outcomes ◽  
Health Concern ◽  
Exposure Level ◽  
Mitochondrial Content ◽  
Mitochondrial Superoxide ◽  
Protein Dissociation

AbstractPerfluorooctane sulfonate (PFOS) has been widely utilized in numerous industries. Due to long environmental and biological half-lives, PFOS is a major public health concern. Although the literature suggests that PFOS may induce neurotoxicity, neurotoxic mechanisms, and neuropathology are poorly understood. Thus, the primary goal of this study was to determine if PFOS is selectively neurotoxic and potentially relevant to specific neurological diseases. Nematodes (Caenorhabditis elegans) were exposed to PFOS or related per- and polyfluoroalkyl substances (PFAS) for 72 h and tested for evidence of neuropathology through examination of cholinergic, dopaminergic, gamma-amino butyric acid (GABA)ergic, and serotoninergic neuronal morphologies. Dopaminergic and cholinergic functional analyses were assessed through 1-nonanol and Aldicarb assay. Mechanistic studies assessed total reactive oxygen species, superoxide ions, and mitochondrial content. Finally, therapeutic approaches were utilized to further examine pathogenic mechanisms. Dopaminergic neuropathology occurred at lower exposure levels (25 ppm, approximately 50 µM) than required to produce neuropathology in GABAergic, serotonergic, and cholinergic neurons (100 ppm, approximately 200 µM). Further, PFOS exposure led to dopamine-dependent functional deficits, without altering acetylcholine-dependent paralysis. Mitochondrial content was affected by PFOS at far lower exposure level than required to induce pathology (≥1 ppm, approximately 2 µM). Perfluorooctane sulfonate exposure also enhanced oxidative stress. Further, mutation in mitochondrial superoxide dismutase rendered animals more vulnerable. Neuroprotective approaches such as antioxidants, PFAS-protein dissociation, and targeted (mitochondrial) radical and electron scavenging were neuroprotective, suggesting specific mechanisms of action. In general, other tested PFAS were less neurotoxic. The primary impact is to prompt research into potential adverse outcomes related to PFAS-induced dopaminergic neurotoxicity in humans.

Environmental exposures impact the nervous system in a life stage-specific manner

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Julia Tigges ◽  
Tamara Schikowski ◽  
Ellen Fritsche
Keyword(s):  
Nervous System ◽  
Life Stage ◽  
Environmental Pollutants ◽  
Toxicity Assessment ◽  
Test Methods ◽  
Adverse Outcomes ◽  
Assessment Process ◽  
Health Concern ◽  
Adverse Health Effects

Abstract Exposure to environmental pollutants like chemicals or air pollution is major health concern for the human population. Especially the nervous system is a sensitive target for environmental toxins with exposures leading to life stage-dependent neurotoxicity. Developmental and adult neurotoxicity are characterized by specific adverse outcomes ranging from neurodevelopmental disorders to neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. The risk assessment process for human health protection is currently undergoing a paradigm change toward new approach methods that allow mechanism-based toxicity assessment. As a flagship project, an in vitro battery of test methods for developmental neurotoxicity evaluation is currently supported by the Organization for Economic Co-operation and Development (OECD). A plethora of stem cell-based methods including brain spheres and organoids are currently further developed to achieve time- and cost-saving tools for linking MoA-based hazards to adverse health effects observed in humans.

scholarly journals Stochastic left–right neuronal asymmetry in Caenorhabditis elegans

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150407 ◽  
Author(s):  
Amel Alqadah ◽  
Yi-Wen Hsieh ◽  
Rui Xiong ◽  
Chiou-Fen Chuang
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Calcium Signalling ◽  
Model Organism ◽  
Brain Asymmetry ◽  
C Elegans ◽  
Left And Right ◽  
Left Right Asymmetry ◽  
Neuronal Asymmetry

Left–right asymmetry in the nervous system is observed across species. Defects in left–right cerebral asymmetry are linked to several neurological diseases, but the molecular mechanisms underlying brain asymmetry in vertebrates are still not very well understood. The Caenorhabditis elegans left and right amphid wing ‘C’ (AWC) olfactory neurons communicate through intercellular calcium signalling in a transient embryonic gap junction neural network to specify two asymmetric subtypes, AWC OFF (default) and AWC ON (induced), in a stochastic manner. Here, we highlight the molecular mechanisms that establish and maintain stochastic AWC asymmetry. As the components of the AWC asymmetry pathway are highly conserved, insights from the model organism C. elegans may provide a window onto how brain asymmetry develops in humans. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Repeated Noise Exposure Does Not Reach Hazardous Levels During Total Joint Arthroplasty

2020 ◽  
Vol 185 (9-10) ◽  
pp. e1551-e1555
Author(s):  
Sean E Slaven ◽  
Benjamin M Wheatley ◽  
Daniel L Christensen ◽  
Sameer K Saxena ◽  
Robert J McGill
Keyword(s):  
Noise Exposure ◽  
Weighted Average ◽  
Sound Level ◽  
Health Concern ◽  
Exposure Level ◽  
Total Knee ◽  
Time Weighted Average ◽  
Exposure Levels ◽  
Occupational Standards ◽  
Level Meter

Abstract Introduction Noise exposure is an occupational health concern for certain professions, especially military servicemembers and those using power tools on a regular basis. The purpose of this study was to quantify noise exposure during total hip arthroplasty (THA) and total knee arthroplasty (TKA) cases compared to the recommended standard for occupational noise exposure. Materials and Methods A sound level meter was used to record cumulative and peak noise exposure levels in 10 primary THA and 10 primary TKA surgeries, as well as 10 arthroscopy cases as controls. Measurements at the distance of the surgeon were taken in all cases. In TKA cases, measurements were taken at 3 feet and 8 feet from the surgeon, to simulate the position of the anesthetist and circulating nurse, respectively. Results Time-weighted average was significantly higher in THA (64.7 ± 5.2 dB) and TKA (64.5 ± 6.8 dB) as compared to arthroscopic cases (51.1 ± 7.5 dB, P < 0.001) and higher at the distance of the surgeon (64.5 ± 6.8 dB) compared to the anesthetist (52.9 ± 3.8 dB) and the circulating nurse (54.8 ± 11.2 dB, P = 0.006). However, time-weighted average was below the recommended exposure level of 85 dB for all arthroplasty cases. Peak levels did not differ significantly between surgery type or staff role, and no values above the ceiling limit of 140 dB were recorded. Surgeon’s daily noise dose percentage per case was 1.78% for THA and 2.04% for TKA. Conclusion Noise exposure in THA and TKA was higher than arthroscopic cases but did not exceed occupational standards. A daily dose percentage of approximately 2% per case indicates that repeated noise exposure likely does not reach hazardous levels in modern arthroplasty practice.

Studies of Emissions from Oil Fires

1999 ◽  
Vol 1999 (1) ◽  
pp. 541-547 ◽  
Author(s):  
Mervin F. Fingas ◽  
Patrick Lambert ◽  
Ken Li ◽  
Zhendi Wang ◽  
Francine Ackerman ◽  
...  
Keyword(s):  
Crude Oil ◽  
Ground Level ◽  
Health Concern ◽  
Exposure Level ◽  
Emission Data ◽  
Combustion Gases ◽  
Aldehydes And Ketones ◽  
Polycyclic Aromatic ◽  
Exposure Levels

ABSTRACT Over 35 meso-scale burns were conducted to study various aspects of diesel and crude oil burning in situ. Extensive sampling and monitoring of these burns were conducted at downwind stations, upwind stations, and in the smoke plume. Particulate samples were taken in air and analyzed for polycyclic aromatic hydrocarbons (PAHs). PAHs were found to be lower in the soot than in the starting oil, although higher concentrations of the larger molecular PAHs were found in the soot and residue, especially for diesel burns. Particulates in the air were measured by several means, and were found to be greater than recommended exposure levels up to 500 meters downwind at ground level, depending on the size and type of fire. Diesel fires emit much more particulate matter and have longer exposure zones. Combustion gases, including carbon dioxide and carbon monoxide, were below exposure level maximums. Volatile organic compound (VOCs) emissions were measured, but the levels were less than from an evaporating crude oil spill. Over 140 compounds were identified and quantified. Carbonyls, including aldehydes and ketones, were found to be below human health concern levels. Emission data from over 30 experimental burns were used to develop prediction equations for over 150 specific compounds or emission categories. These were used to calculate safe distances and levels of concern for a standard burn size of 500 square meters, an amount that would typically be contained in a boom. The safe distance for a crude oil burn of this size is about 500 m and for a diesel burn, much farther.

Addressing Food Insecurity and Overweight/Obesity in Hospitalized Low-Income Latino Patients

2019 ◽  
Vol 25 (3) ◽  
pp. 241-248
Author(s):  
Trina Lorraine Gipson-Jones ◽  
Bertha L. Davis ◽  
Ché Matthew Harris
Keyword(s):  
Public Health ◽  
Type 2 Diabetes ◽  
Food Insecurity ◽  
Low Income ◽  
Adverse Outcomes ◽  
Hospital Utilization ◽  
Health Concern ◽  
Public Health Concern ◽  
Disease Risks

Food insecurity (FI), the limited or unreliable availability of safe and nutritious food, is a pressing public health concern affecting millions of U.S. citizens. Unfortunately, FI tends to impact those who are most vulnerable (e.g., low-income minorities) and potentially increases obesity risks, diet-sensitive disease risks (e.g., hypertension and type 2 diabetes), and hospital utilization. Low-income Latino patients may be particularly sensitive to adverse outcomes based on unaddressed socioeconomic needs. Nurses are in a prime position to assess and address FI in these patients. Our article will discuss how nurses can be advocates in combating FI in Latino patients with overweight/obesity.

scholarly journals Choline Transport and de novo Choline Synthesis Support Acetylcholine Biosynthesis in Caenorhabditis elegans Cholinergic Neurons

Genetics ◽  
2007 ◽  
Vol 177 (1) ◽  
pp. 195-204 ◽  
Author(s):  
Gregory P. Mullen ◽  
Eleanor A. Mathews ◽  
Mai H. Vu ◽  
Jerrod W. Hunter ◽  
Dennis L. Frisby ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
De Novo ◽  
Cholinergic Neurons ◽  
Choline Transport

scholarly journals Mitochondrial Dysfunction Confers Resistance to Multiple Drugs in Caenorhabditis elegans

2010 ◽  
Vol 21 (6) ◽  
pp. 956-969 ◽  
Author(s):  
Iryna O. Zubovych ◽  
Sarah Straud ◽  
Michael G. Roth
Keyword(s):  
Drug Resistance ◽  
Caenorhabditis Elegans ◽  
Mitochondrial Protein ◽  
Drug Resistant ◽  
Wild Type ◽  
C Elegans ◽  
Mitochondrial Inhibitors ◽  
Mitochondrial Superoxide ◽  
Genes Encoding ◽  
Multiple Drugs

In a previous genetic screen for Caenorhabditis elegans mutants that survive in the presence of an antimitotic drug, hemiasterlin, we identified eight strong mutants. Two of these were found to be resistant to multiple toxins, and in one of these we identified a missense mutation in phb-2, which encodes the mitochondrial protein prohibitin 2. Here we identify two additional mutations that confer drug resistance, spg-7 and har-1, also in genes encoding mitochondrial proteins. Other mitochondrial mutants, isp-1, eat-3, and clk-1, were also found to be drug-resistant. Respiratory complex inhibitors, FCCP and oligomycin, and a producer of reactive oxygen species (ROS), paraquat, all rescued wild-type worms from hemiasterlin toxicity. Worms lacking mitochondrial superoxide dismutase (MnSOD) were modestly drug-resistant, and elimination of MnSOD in the phb-2, har-1, and spg-7 mutants enhanced resistance. The antioxidant N-acetyl-l-cysteine prevented mitochondrial inhibitors from rescuing wild-type worms from hemiasterlin and sensitized mutants to the toxin, suggesting that a mechanism sensitive to ROS is necessary to trigger drug resistance in C. elegans. Using genetics, we show that this drug resistance requires pkc-1, the C. elegans ortholog of human PKCε.

scholarly journals An economical and highly adaptable optogenetics system for individual and population-level manipulation of Caenorhabditis elegans

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
M. Koopman ◽  
L. Janssen ◽  
E. A. A. Nollen
Keyword(s):  
Caenorhabditis Elegans ◽  
Light Stimulus ◽  
Cholinergic Neurons ◽  
Model Organisms ◽  
Parameter Study ◽  
Multiple Model ◽  
Excitable Cells ◽  
Specific Expression ◽  
C Elegans ◽  
Age Related

Abstract Background Optogenetics allows the experimental manipulation of excitable cells by a light stimulus without the need for technically challenging and invasive procedures. The high degree of spatial, temporal, and intensity control that can be achieved with a light stimulus, combined with cell type-specific expression of light-sensitive ion channels, enables highly specific and precise stimulation of excitable cells. Optogenetic tools have therefore revolutionized the study of neuronal circuits in a number of models, including Caenorhabditis elegans. Despite the existence of several optogenetic systems that allow spatial and temporal photoactivation of light-sensitive actuators in C. elegans, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, modular, and adjustable optogenetics device for use on different microscopes and worm trackers, which we called the OptoArm. Results The OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles, and light color. We demonstrate OptoArm’s power in a population-based multi-parameter study on the contributions of motor circuit cells to age-related motility decline. We found that individual components of the neuromuscular system display different rates of age-dependent deterioration. The functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit ageing. Conclusion We have assembled an economical, reliable, and highly adaptable optogenetics system which can be deployed to address diverse biological questions. We provide a detailed description of the construction as well as technical and biological validation of our set-up. Importantly, use of the OptoArm is not limited to C. elegans and may benefit studies in multiple model organisms, making optogenetics more accessible to the broader research community.

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