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Mancozeb-induced behavioral deficits precede structural neural degeneration
A Harrison Brody1, Eunice Chou, Janet M Gray
1Program in Neuroscience and Behavior, Poughkeepsie, NY, USA. albrody@vassar.edu
Abstract:
Manganese-containing fungicides like Mancozeb have been associated with neurodegenerative conditions like Parkinson's disease. We examined the behavioral damage and differential neuronal vulnerability resulting from Mancozeb exposure using Caenorhabditis elegans, an important mid-trophic level soil organism that is also a powerful model for studying mechanisms of environmental pollutant-induced neurodegenerative disease. The dopamine-mediated swim to crawl locomotory transition behavior is exquisitely vulnerable to Mancozeb, with functional impairment preceding markers of neuronal structural damage. The damage is partially rescued in mutants lacking the divalent metal transporter, SMF-1, demonstrating that some, but not all, of the damage is mediated by manganese. Increasing concentrations of Mancozeb recruit additional behavioral dysfunction, notably serotonin-mediated egg-laying behavior, but without evident serotonergic neuronal structural damage. Thus, measurements of behavioral dysfunction are a sensitive early marker of fungicide toxicity that could be exploited to examine further mechanisms of neuron damage and possible therapeutic interventions. These results also provide important insight into the consequences of fungicide use on the ecological behavior of nematodes.
Insights
Mancozeb fungicide exposure causes neurotoxicity in nematodes, impairing dopamine-mediated movement. Manganese contributes to this damage, highlighting behavioral changes as early indicators of fungicide neurotoxicity.
Area of Science:
- Environmental toxicology
- Neuroscience
- Ecotoxicology
Background:
- Manganese-containing fungicides, such as Mancozeb, are linked to neurodegenerative diseases.
- Environmental pollutants can induce neurodegenerative conditions.
- Caenorhabditis elegans serves as a model organism for studying neurodegenerative disease mechanisms.
Purpose of the Study:
- To investigate the neurobehavioral effects of Mancozeb exposure in Caenorhabditis elegans.
- To determine the role of manganese in Mancozeb-induced neurotoxicity.
- To identify early biomarkers of fungicide neurotoxicity.
Main Methods:
- Utilized Caenorhabditis elegans as a model organism.
- Assessed dopamine-mediated swim-to-crawl transition behavior.
- Examined serotonin-mediated egg-laying behavior.
- Investigated manganese transport using SMF-1 mutants.
Main Results:
- Mancozeb exposure impairs dopamine-mediated locomotion before structural neuronal damage.
- Manganese transport via SMF-1 partially mediates Mancozeb-induced damage.
- Higher Mancozeb concentrations affect serotonin-mediated egg-laying behavior without evident structural damage.
- Behavioral dysfunction serves as a sensitive marker for fungicide toxicity.
Conclusions:
- Behavioral assays are sensitive indicators of early-stage fungicide neurotoxicity.
- Mancozeb's neurotoxic effects involve manganese-dependent and independent pathways.
- Understanding fungicide impacts on nematode behavior is crucial for ecological risk assessment.
