Developmental lead exposure affects dopaminergic neuron morphology and modifies basal slowing response in Caenorhabditis elegans: Effects of ethanol

Albrecht, Paula A.; Fernandez-Hubeid, Lucia E.; Deza-Ponzio, Romina; Martins, Airton C.; Aschner, Michael; Virgolini, Miriam Beatríz

doi:10.1016/j.neuro.2022.06.005

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…Interestingly, this response was improved after EtOH (200 mm) only in the Pb-exposed animals that overexpress tyrosine hydroxylase (TH) or are null-mutant of the vesicular transporter (VMAT), whereas the strains lacking the DOP-4 receptor or TH-deficient showed a non-significant-reversal by the drug. These results suggest that EtOH may exert a compensatory effect in the DAergic synapse functional alterations reported in the Pb-exposed animals ( Albrecht P. A. et al, 2022 ).…”

Section: Introductionmentioning

confidence: 68%

The intertwining between lead and ethanol in the model organism Caenorhabditis elegans

Albrecht

Fernandez-Hubeid²,

Deza-Ponzio³

et al. 2022

Front. Toxicol.

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Caenorhabditis elegans (C. elegans) is a model organism widely used to evaluate the mechanistic aspects of toxicants with the potential to predict responses comparable to those of mammals. We report here the consequences of developmental lead (Pb) exposure on behavioral responses to ethanol (EtOH) in C. elegans. In addition, we present data on morphological alterations in the dopamine (DA) synapse and DA-dependent behaviors aimed to dissect the neurobiological mechanisms that underlie the relationship between these neurotoxicants. Finally, the escalation to superior animals that parallels the observed effects in both experimental models with references to EtOH metabolism and oxidative stress is also discussed. Overall, the literature revised here underpins the usefulness of C. elegans to evidence behavioral responses to a combination of neurotoxicants in mechanistic-orientated studies.

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Section: Introductionmentioning

confidence: 68%

The intertwining between lead and ethanol in the model organism Caenorhabditis elegans

Albrecht

Fernandez-Hubeid²,

Deza-Ponzio³

et al. 2022

Front. Toxicol.

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“…Because they show degeneration earlier than the cell bodies, dendrites are often the focus when studying neurodegeneration in CEP neurons (15,20,(33)(34)(35). Thus, the first step of the algorithm automatically crops the images such that only the dendrites are in view.…”

Section: Dendrite Detectionmentioning

confidence: 99%

An unbiased, automated platform for scoring dopaminergic neurodegeneration inC. elegans

Clark

Kalmanson

Morton

et al. 2023

Preprint

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Caenorhabditis elegans (C. elegans) has served as a simple model organism to study dopaminergic neurodegeneration, as it enables quantitative analysis of cellular and sub-cellular morphologies in live animals. These isogenic nematodes have a rapid life cycle and transparent body, making high-throughput imaging and evaluation of fluorescently tagged neurons possible. However, the current state-of-the-art method for quantifying dopaminergic degeneration requires researchers to manually examine images and score dendrites into groups of varying levels of neurodegeneration severity, which is time consuming, subject to bias, and limited in data sensitivity. We aim to overcome the pitfalls of manual neuron scoring by developing an automated, unbiased image processing algorithm to quantify dopaminergic neurodegeneration in C. elegans. The algorithm can be used on images acquired with different microscopy setups and only requires two inputs: a maximum projection image of the four cephalic neurons in the C. elegans head and the pixel size of the user’s camera. We validate the platform by detecting and quantifying neurodegeneration in nematodes exposed to rotenone, cold shock, and 6-hydroxydopamine using 63x epifluorescence, 63x confocal, and 40x epifluorescence microscopy, respectively. Analysis of tubby mutant worms with altered fat storage showed that, contrary to our hypothesis, increased adiposity did not sensitize to stressor-induced neurodegeneration. We further verify the accuracy of the algorithm by comparing code-generated, categorical degeneration results with manually scored dendrites of the same experiments. The platform, which detects 19 different metrics of neurodegeneration, can provide comparative insight into how each exposure affects dopaminergic neurodegeneration patterns.

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“…Dendrite detection. Because they show degeneration earlier than the cell bodies, dendrites are often the focus when studying neurodegeneration in CEP neurons [15,20,[34][35][36]. Thus, the first step of the algorithm automatically crops the images such that only the dendrites are in view.…”

Section: A Unbiased Automatic Algorithm For Neurodegeneration Detectionmentioning

confidence: 99%

An unbiased, automated platform for scoring dopaminergic neurodegeneration in C. elegans

et al. 2023

View full text Add to dashboard Cite

Caenorhabditis elegans (C. elegans) has served as a simple model organism to study dopaminergic neurodegeneration, as it enables quantitative analysis of cellular and sub-cellular morphologies in live animals. These isogenic nematodes have a rapid life cycle and transparent body, making high-throughput imaging and evaluation of fluorescently tagged neurons possible. However, the current state-of-the-art method for quantifying dopaminergic degeneration requires researchers to manually examine images and score dendrites into groups of varying levels of neurodegeneration severity, which is time consuming, subject to bias, and limited in data sensitivity. We aim to overcome the pitfalls of manual neuron scoring by developing an automated, unbiased image processing algorithm to quantify dopaminergic neurodegeneration in C. elegans. The algorithm can be used on images acquired with different microscopy setups and only requires two inputs: a maximum projection image of the four cephalic neurons in the C. elegans head and the pixel size of the user’s camera. We validate the platform by detecting and quantifying neurodegeneration in nematodes exposed to rotenone, cold shock, and 6-hydroxydopamine using 63x epifluorescence, 63x confocal, and 40x epifluorescence microscopy, respectively. Analysis of tubby mutant worms with altered fat storage showed that, contrary to our hypothesis, increased adiposity did not sensitize to stressor-induced neurodegeneration. We further verify the accuracy of the algorithm by comparing code-generated, categorical degeneration results with manually scored dendrites of the same experiments. The platform, which detects 20 different metrics of neurodegeneration, can provide comparative insight into how each exposure affects dopaminergic neurodegeneration patterns.

show abstract

Developmental lead exposure affects dopaminergic neuron morphology and modifies basal slowing response in Caenorhabditis elegans: Effects of ethanol

Cited by 7 publications

References 49 publications

The intertwining between lead and ethanol in the model organism Caenorhabditis elegans

The intertwining between lead and ethanol in the model organism Caenorhabditis elegans

An unbiased, automated platform for scoring dopaminergic neurodegeneration inC. elegans

An unbiased, automated platform for scoring dopaminergic neurodegeneration in C. elegans

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