Selenomethionine reduces visual deficits due to developmental methylmercury exposures.
Developmental exposures to methylmercury (MeHg) have life-long behavioral effects. Many micronutrients, including selenium, are involved in cellular defenses against oxidative stress and may reduce the severity of MeHg-induced deficits. Zebrafish embryos (<4 h post fertilization, hpf) were exposed to combinations of 0.0-0.30 microM MeHg and/or selenomethionine (SeMet) until 24 hpf then placed in clean medium. Fish were tested as adults under low light conditions ( approximately 60 microW/m(2)) for visual responses to a rotating black bar. Dose-dependent responses to MeHg exposure were evident (ANOVA, P<0.001) as evidenced by reduced responsiveness, whereas SeMet did not induce deficits except at 0.3 microM. Ratios of SeMet:MeHg of 1:1 or 1:3 resulted in responses that were indistinguishable from controls (ANOVA, P<0.001). No gross histopathologies were observed (H&E stain) in the retina or optic tectum at any MeHg concentration. Whole-cell, voltage-gated, depolarization-elicited outward K(+) currents of bipolar cells in intact retina of slices adult zebrafish were recorded and outward K(+) current amplitude was larger in bipolar cells of MeHg-treated fish. This was due to the intense response of cells expressing the delayed rectifying I(K) current; cells expressing the transient I(A) current displayed a slight trend for smaller amplitude among MeHg-treated fish. Developmental co-exposure to SeMet reduced but did not eliminate the increase in the MeHg-induced I(K) response, however, I(A) responses increased significantly over MeHg-treated fish to match control levels. Electrophysiological deficits parallel behavioral patterns in MeHg-treated fish, i.e., initial reactions to the rotating bar were followed by periods of inactivity and then a resumption of responses.
Weber
Daniel N
DN
Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee, 600 E. Greenfield Ave., Milwaukee, WI 53204, United States. dweber@uwm.edu
Connaughton
Victoria P
VP
Dellinger
John A
JA
Klemer
David
D
Udvadia
Ava
A
Carvan
Michael J
MJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004596:Electroretinography; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D008297:Male; D020262:Mercury Poisoning, Nervous System / Q000517:prevention & control*; D008767:Methylmercury Compounds / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011297:Prenatal Exposure Delayed Effects; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D051245:Retinal Bipolar Cells / Q000187:drug effects* / Q000502:physiology; D012645:Selenomethionine / Q000494:pharmacology*; D013477:Superior Colliculi / Q000187:drug effects* / Q000196:embryology; D014795:Visual Pathways / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D015027:Zebrafish
D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D015221:Potassium Channels; D012645:Selenomethionine