Chronic exposure to rotenone models sporadic Parkinson's disease in Drosophila melanogaster.
Parkinson's disease (PD) is a movement disorder characterized by the selective degeneration of nigrostriatal dopaminergic neurons. Both familial and sporadic cases present tremor, rigidity, slowness of movement, and postural instability. Although major insights into the genes responsible for some rare hereditary cases have arisen, the etiology of sporadic cases remains unknown. Epidemiological studies have suggested an association with environmental toxins, mainly mitochondrial complex I inhibitors such as the widely used pesticide rotenone. In recent years, Drosophila melanogaster has been used as a model of several neurodegenerative diseases, including a genetic model of PD. Here, we studied the neurodegenerative and behavioral effects of a sublethal chronic exposure to rotenone in Drosophila. After several days, the treated flies presented characteristic locomotor impairments that increased with the dose of rotenone. Immunocytochemistry analysis demonstrated a dramatic and selective loss of dopaminergic neurons in all of the brain clusters. The addition of l-dopa (3,4-dihydroxy-L-phenylalanine) into the feeding medium rescued the behavioral deficits but not neuronal death, as is the case in human PD patients. In contrast, the antioxidant melatonin (N-acetyl-5-methoxytryptamine) alleviated both symptomatic impairment and neuronal loss, supporting the idea that this agent may be beneficial in the treatment of PD. Therefore, chronic exposure to pesticides recapitulates key aspects of PD in Drosophila and provides a new in vivo model for studying the mechanisms of dopaminergic neurodegeneration.
Coulom
Hélène
H
Laboratoire de Génétique et Physiologie du Développement, Centre National de la Recherche Scientifique, UniversitédelaMéditerranée, Developmental Biology Institute of Marseille, Campus de Luminy, F-13288 Marseille Cedex 9, France.
Birman
Serge
S
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D004298:Dopamine / Q000032:analysis; D018491:Dopamine Agonists / Q000627:therapeutic use; D004331:Drosophila melanogaster / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D007306:Insecticides / Q000633:toxicity*; D007980:Levodopa / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012402:Rotenone / Q000633:toxicity*
D000975:Antioxidants; D018491:Dopamine Agonists; D007306:Insecticides; D012402:Rotenone; D007980:Levodopa; D042967:Electron Transport Complex I; D008550:Melatonin; D004298:Dopamine