Chronic exposure to methylmercury induces puncta formation in cephalic dopaminergic neurons in Caenorhabditis elegans

Tao Ke, Aristidis Tsatsakis, Abel Santamaría, Félix Alexandre Antunes Soare, Alexey A. Tinkov, Anca Oana Docea, Anatoly Skalny, Aaron B. Bowman, Michael Aschner

Research output: Contribution to journalArticle

Abstract

The neurotransmitter dopamine is a neuromodulator in the positive and negative regulation of brain circuits. Dopamine insufficiency or overload has been implicated in aberrant activities of neural circuits that play key roles in the pathogenesis of neurological and psychiatric diseases. Dopaminergic neurons are vulnerable to environmental insults. The neurotoxin methylmercury (MeHg) produces dopaminergic neuron damage in rodent as well as in Caenorhabditis elegans (C. elegans) models. Previous studies have demonstrated the utility of C. elegans as an alternative and complementary experimental model in dissecting out mechanism of MeHg-induced dopaminergic neurodegeneration. However, a sensitive pathological change that marks early events in neurodegeneration induced by environmental level of MeHg, is still lacking. By establishing a chronic exposure C. elegans model, for the first time, we have shown the propensity of MeHg (5 μM, 10 days) to induce bright puncta of dat-1::mCherry aggreagtes in the dendrites of cephalic (2 CEPs) dopaminergic neurons in a dose- and time-dependent manner, while these changes were not found in other dopaminergic neurons: anterior deirids (2 ADEs) and posterior deirids (2 PDEs), cholinergic neurons (2 AIYs) or glutamatergic neurons (2 PVDs). The bright puncta appear as an aggregation of mCherry proteins accumulating in dendrites. Further staining shows that the puncta were not inclusions in lysosome, or amyloid protein aggregates. In addition, features of the puncta including enlarged sphere shape (0.5–2 μm diameters), bright and accompanying with the shrinkage of the dendrite suggest that the puncta are likely composed of homologous mCherry molecules packaged at the dendritic site for exportation. Moreover, in the glutathione S-transferase 4 (gst-4) transcriptional reporter strain and RT-PCR assay, the expression levels of gst-4 and tubulins (tba-1 and tba-2) genes were not significantly modified under this chronic exposure paradigm, but gst-4 did show significant changes in an one day exposure paradigm. Collectively, these results suggest that CEP dopaminergic neurons are a sensitive target of MeHg, and the current exposure paradigm could be used as a model to investigate mechanism of dopaminergic neurotoxicity.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalNeuroToxicology
Volume77
DOIs
StatePublished - Mar 2020

Fingerprint

Dopaminergic Neurons
Caenorhabditis elegans
Neurons
Head
Dendrites
Glutathione Transferase
Neurotransmitter Agents
Dopamine
Amyloidogenic Proteins
Cholinergic Neurons
Neurotoxins
Tubulin
Lysosomes
Psychiatry
Rodentia
Networks (circuits)
Theoretical Models
Physical vapor deposition
Staining and Labeling
Cholinergic Agents

Keywords

  • C. elegansdopamine
  • Methylmercury
  • puncta formation
  • Toxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Chronic exposure to methylmercury induces puncta formation in cephalic dopaminergic neurons in Caenorhabditis elegans. / Ke, Tao; Tsatsakis, Aristidis; Santamaría, Abel; Antunes Soare, Félix Alexandre; Tinkov, Alexey A.; Docea, Anca Oana; Skalny, Anatoly; Bowman, Aaron B.; Aschner, Michael.

In: NeuroToxicology, Vol. 77, 03.2020, p. 105-113.

Research output: Contribution to journalArticle

Ke, T, Tsatsakis, A, Santamaría, A, Antunes Soare, FA, Tinkov, AA, Docea, AO, Skalny, A, Bowman, AB & Aschner, M 2020, 'Chronic exposure to methylmercury induces puncta formation in cephalic dopaminergic neurons in Caenorhabditis elegans', NeuroToxicology, vol. 77, pp. 105-113. https://doi.org/10.1016/j.neuro.2020.01.003
Ke, Tao ; Tsatsakis, Aristidis ; Santamaría, Abel ; Antunes Soare, Félix Alexandre ; Tinkov, Alexey A. ; Docea, Anca Oana ; Skalny, Anatoly ; Bowman, Aaron B. ; Aschner, Michael. / Chronic exposure to methylmercury induces puncta formation in cephalic dopaminergic neurons in Caenorhabditis elegans. In: NeuroToxicology. 2020 ; Vol. 77. pp. 105-113.
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