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Delayed effects of methylmercury on the mitochondria of dopaminergic neurons and developmental toxicity in zebrafish larvae (Danio rerio).
Aquat Toxicol 2016; 175:73-80AT

Abstract

Methylmercury (MeHg) is a known neurotoxicant affecting the central nervous system but effects on dopaminergic (DA) neurons are not well understood. Wild-type zebrafish (Danio rerio) and two transgenic lines: Tg(dat:eGFP) expressing enhanced green fluorescent protein (eGFP) in DA neuron clusters and Tg(dat:tom20 MLS-mCherry) expressing red fluorescence (mCherry) targeted to mitochondria of DA neurons were used to evaluate the effects of micromolar MeHg exposure on DA neuron and whole animal motor function during early development. Three-day-old larvae were exposed to micromolar concentrations of MeHg (0.03, 0.06, and 0.3μM) in system water. Exposure to 0.3μM MeHg caused mortality and significant morphological abnormalities including edema, curvature of the spine, and hemorrhages in zebrafish larvae after a 48h exposure period. At 0.06μM MeHg, the appearance of morphological abnormalities was delayed for 72h and far less severe, whereas 0.03μM MeHg did not cause any morphological defects or mortalities. A delayed but significant reduction in locomotor ability and mCherry fluorescence in specific brain regions in the 0.06μM MeHg exposed larvae suggests that DA neuron function rather than neuron numbers was compromised. Double immunolabeling with tyrosine hydroxylase and pan neural staining showed no effect of MeHg exposure. We have established Tg(dat:tom20 MLS-mCherry) zebrafish larvae as a model which can be used to assess MeHg neurotoxicity and that exposure to low dose MeHg (0.06μM) during development may predispose DA neurons to impairment caused by changes in mitochondrial dynamics.

Authors+Show Affiliations

Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada.Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada.Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada.Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada.Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ontario K1N 6N5, Canada. Electronic address: laurie.chan@uottawa.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26994370

Citation

Huang, Susie S Y., et al. "Delayed Effects of Methylmercury On the Mitochondria of Dopaminergic Neurons and Developmental Toxicity in Zebrafish Larvae (Danio Rerio)." Aquatic Toxicology (Amsterdam, Netherlands), vol. 175, 2016, pp. 73-80.
Huang SS, Noble S, Godoy R, et al. Delayed effects of methylmercury on the mitochondria of dopaminergic neurons and developmental toxicity in zebrafish larvae (Danio rerio). Aquat Toxicol. 2016;175:73-80.
Huang, S. S., Noble, S., Godoy, R., Ekker, M., & Chan, H. M. (2016). Delayed effects of methylmercury on the mitochondria of dopaminergic neurons and developmental toxicity in zebrafish larvae (Danio rerio). Aquatic Toxicology (Amsterdam, Netherlands), 175, pp. 73-80. doi:10.1016/j.aquatox.2016.03.004.
Huang SS, et al. Delayed Effects of Methylmercury On the Mitochondria of Dopaminergic Neurons and Developmental Toxicity in Zebrafish Larvae (Danio Rerio). Aquat Toxicol. 2016;175:73-80. PubMed PMID: 26994370.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delayed effects of methylmercury on the mitochondria of dopaminergic neurons and developmental toxicity in zebrafish larvae (Danio rerio). AU - Huang,Susie S Y, AU - Noble,Sandra, AU - Godoy,Rafael, AU - Ekker,Marc, AU - Chan,Hing Man, Y1 - 2016/03/07/ PY - 2016/02/01/received PY - 2016/03/03/revised PY - 2016/03/04/accepted PY - 2016/3/20/entrez PY - 2016/3/20/pubmed PY - 2016/12/20/medline KW - Delayed response KW - Dopaminergic neuron KW - Low dose exposure KW - Methylmercury KW - Mitochondria SP - 73 EP - 80 JF - Aquatic toxicology (Amsterdam, Netherlands) JO - Aquat. Toxicol. VL - 175 N2 - Methylmercury (MeHg) is a known neurotoxicant affecting the central nervous system but effects on dopaminergic (DA) neurons are not well understood. Wild-type zebrafish (Danio rerio) and two transgenic lines: Tg(dat:eGFP) expressing enhanced green fluorescent protein (eGFP) in DA neuron clusters and Tg(dat:tom20 MLS-mCherry) expressing red fluorescence (mCherry) targeted to mitochondria of DA neurons were used to evaluate the effects of micromolar MeHg exposure on DA neuron and whole animal motor function during early development. Three-day-old larvae were exposed to micromolar concentrations of MeHg (0.03, 0.06, and 0.3μM) in system water. Exposure to 0.3μM MeHg caused mortality and significant morphological abnormalities including edema, curvature of the spine, and hemorrhages in zebrafish larvae after a 48h exposure period. At 0.06μM MeHg, the appearance of morphological abnormalities was delayed for 72h and far less severe, whereas 0.03μM MeHg did not cause any morphological defects or mortalities. A delayed but significant reduction in locomotor ability and mCherry fluorescence in specific brain regions in the 0.06μM MeHg exposed larvae suggests that DA neuron function rather than neuron numbers was compromised. Double immunolabeling with tyrosine hydroxylase and pan neural staining showed no effect of MeHg exposure. We have established Tg(dat:tom20 MLS-mCherry) zebrafish larvae as a model which can be used to assess MeHg neurotoxicity and that exposure to low dose MeHg (0.06μM) during development may predispose DA neurons to impairment caused by changes in mitochondrial dynamics. SN - 1879-1514 UR - https://www.unboundmedicine.com/medline/citation/26994370/Delayed_effects_of_methylmercury_on_the_mitochondria_of_dopaminergic_neurons_and_developmental_toxicity_in_zebrafish_larvae__Danio_rerio__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-445X(16)30056-X DB - PRIME DP - Unbound Medicine ER -