TY - JOUR
T1 - Early-life exposure to methylmercury in wildtype and pdr-1/parkin knockout C. elegans
AU - Martinez-Finley, Ebany J.
AU - Chakraborty, Sudipta
AU - Slaughter, James C.
AU - Aschner, Michael
N1 - Funding Information:
Acknowledgments This work was supported by the National Institute of Environmental Health Sciences (NIEHS) [R01ES07331, T32 ES007028] and the National Institutes of Health Loan Repayment Program. We would like to acknowledge the C. elegans Reverse Genetics Core Facility at UBC, which is part of the International C. elegans Gene Knockout Consortium and the Caenorhabditis Genetic Center (CGC) for providing the strains used in this manuscript. The authors would also like to acknowledge contributions from Chris Muller.
PY - 2013/8
Y1 - 2013/8
N2 - We examined the impact of early-life exposure to methylmercury (MeHg) on Caenorhabditis elegans (C. elegans) pdr-1 mutants, addressing gene-environment interactions. We tested the hypothesis that early-life exposure to MeHg and knockout (KO) of pdr-1 (mammalian: parkin/PARK2) exacerbates MeHg toxicity and damage to the dopaminergic (DAergic) system. pdr-1KO worms showed increased lethality and decreased lifespan following MeHg exposure. Mercury (Hg) content, measured with inductively coupled plasma-mass spectrometry was increased in pdr-1KO worms compared to wildtype (N2) controls. 2′7′ dichlorodihydrofluorescein diacetate assay revealed a significant increase in reactive oxygen species in both strains following MeHg exposure; however, while N2 worms showed an increase in skn-1 transcript levels following MeHg exposure, there was no difference in skn-1 induction in pdr-1KO worms. Dopamine-dependent behavioral analysis revealed an effect of MeHg on N2 wildtype worms, but no effect on pdr-1KO worms. Taken together, these results suggest that pdr-1KO worms are more sensitive to MeHg than wildtype worms, but MeHg does not exacerbate behavioral changes related to the absence of pdr-1.
AB - We examined the impact of early-life exposure to methylmercury (MeHg) on Caenorhabditis elegans (C. elegans) pdr-1 mutants, addressing gene-environment interactions. We tested the hypothesis that early-life exposure to MeHg and knockout (KO) of pdr-1 (mammalian: parkin/PARK2) exacerbates MeHg toxicity and damage to the dopaminergic (DAergic) system. pdr-1KO worms showed increased lethality and decreased lifespan following MeHg exposure. Mercury (Hg) content, measured with inductively coupled plasma-mass spectrometry was increased in pdr-1KO worms compared to wildtype (N2) controls. 2′7′ dichlorodihydrofluorescein diacetate assay revealed a significant increase in reactive oxygen species in both strains following MeHg exposure; however, while N2 worms showed an increase in skn-1 transcript levels following MeHg exposure, there was no difference in skn-1 induction in pdr-1KO worms. Dopamine-dependent behavioral analysis revealed an effect of MeHg on N2 wildtype worms, but no effect on pdr-1KO worms. Taken together, these results suggest that pdr-1KO worms are more sensitive to MeHg than wildtype worms, but MeHg does not exacerbate behavioral changes related to the absence of pdr-1.
KW - Dopamine
KW - Early-life exposure
KW - Large amino acid transporter
KW - Methylmercury
KW - Parkin
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U2 - 10.1007/s11064-013-1054-8
DO - 10.1007/s11064-013-1054-8
M3 - Article
C2 - 23609499
AN - SCOPUS:84879689165
SN - 0364-3190
VL - 38
SP - 1543
EP - 1552
JO - Neurochemical Research
JF - Neurochemical Research
IS - 8
ER -