title: Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.
abstract: Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders.
authors.affiliation: NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Electronic address: ved.chauhan@opwdd.ny.gov.
authors.forename: Ved
authors.initials: V
authors.lastname: Chauhan
authors.affiliation: NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Abha
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D000284:Administration, Oral; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008767:Methylmercury Compounds / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D008767:Methylmercury Compounds; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D000431:Ethanol; C031280:pyrazole; D000426:Alcohol Dehydrogenase
keywords: Alcohol; Alcohol dehydrogenase; Autism; Developmental disorders; Fetal alcohol spectrum disorder; Methylmercury; Oxidative stress