A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.
Identifieur interne : 001264 ( Ncbi/Curation ); précédent : 001263; suivant : 001265A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.
Auteurs : Thomas Riemensperger [Allemagne] ; Abdul-Raouf Issa ; Ulrike Pech ; Hélène Coulom ; M Vân Nguy ; Marlène Cassar ; Mélanie Jacquet ; André Fiala ; Serge BirmanSource :
- Cell reports [ 2211-1247 ] ; 2013.
English descriptors
- KwdEn :
- Animals, Animals, Genetically Modified, Brain (metabolism), Disease Models, Animal, Dopamine (metabolism), Dopaminergic Neurons (metabolism), Drosophila Proteins (metabolism), Drosophila melanogaster (metabolism), Female, Green Fluorescent Proteins (genetics), Humans, Locomotion (genetics), Locomotion (physiology), Mushroom Bodies (innervation), Oxidative Stress, Parkinson Disease (metabolism), Parkinson Disease (physiopathology), Reflex, Startle (genetics), Reflex, Startle (physiology), Signal Transduction, TRPC Cation Channels (metabolism), alpha-Synuclein (biosynthesis), alpha-Synuclein (genetics).
- MESH :
- chemical , biosynthesis : alpha-Synuclein.
- chemical , genetics : Green Fluorescent Proteins, alpha-Synuclein.
- chemical , metabolism : Dopamine, Drosophila Proteins, TRPC Cation Channels.
- genetics : Locomotion, Reflex, Startle.
- innervation : Mushroom Bodies.
- metabolism : Brain, Dopaminergic Neurons, Drosophila melanogaster, Parkinson Disease.
- physiology : Locomotion, Reflex, Startle.
- physiopathology : Parkinson Disease.
- Animals, Animals, Genetically Modified, Disease Models, Animal, Female, Humans, Oxidative Stress, Signal Transduction.
Abstract
Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.
DOI: 10.1016/j.celrep.2013.10.032
PubMed: 24239353
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pubmed:24239353Le document en format XML
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<term>alpha-Synuclein (genetics)</term>
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<front><div type="abstract" xml:lang="en">Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.</div>
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