title: [Copper intoxication decreases lifespan and induces neurologic alterations in Drosophila melanogaster].
abstract: Wilson disease is a hereditary disorder caused by mutations of the ATP7B gene, which leads to intoxication with copper as a result of an unbalance of copper homeostasis. The clinical manifestations resulting from this intoxication are related to the affectation of liver and the encephalon in most cases. Several animal models are currently available for the study of the malady. However, in such models no neurological symptoms are observed, which limits their use for the study of pathogenic effects of this disease on the central nervous system. The aim of the present study was to evaluate if copper feeding could induce a disease state in Drosophila melanogaster to model Wilson disease. The effect of the feeding of copper at the doses of 31 microM and 47 microM on the survival was initially evaluated. Next, behavioral experiments were conducted to determine whether the motor performance was altered by the 47 microM concentration. The results suggest that copper treatment decreases the viability of the flies. In addition, the decrease of viability was associated to an increase and decrease of spontaneous motor activity at early and late stages of the intoxication, respectively. Finally, the role of the dopaminergic neurotransmission system on the observed motor alterations was evaluated. The dopamine precursor L-dopa increased motor activity. In contrast, D2 receptor antagonist, Fluphenazine, was able to block both the increase and decrease of motor activity scores induced by copper. These results suggest that Drosophila melanogaster could be used as a model organism for the study of possible interventions with potential neuroprotective effects in Wilson disease.
authors.affiliation: Sección de Neuroquímica Clínica, Instituto de Investigaciones Clínicas Dr. Américo Negrette, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela. jlarcaya@yahoo.com
authors.forename: José Luis
authors.initials: JL
authors.lastname: Arcaya
authors.forename: Carlos Mario
authors.initials: CM
authors.lastname: Tejeda
authors.forename: Ubalguis
authors.initials: U
authors.lastname: Salazar
authors.forename: Ernesto José
authors.initials: EJ
authors.lastname: Silva
authors.forename: Karla
authors.initials: K
authors.lastname: Urdaneta
authors.forename: Krystal
authors.initials: K
authors.lastname: Varela
mesh_terms: D000367:Age Factors; D000818:Animals; D019327:Copper Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D018450:Disease Progression; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D059290:Dopaminergic Neurons / Q000187:drug effects; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005476:Fluphenazine / Q000494:pharmacology; D006527:Hepatolenticular Degeneration; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008136:Longevity / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D012494:Sampling Studies; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D015259:Dopamine Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007980:Levodopa; D019327:Copper Sulfate; D005476:Fluphenazine