A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.
Identifieur interne : 000D86 ( Main/Exploration ); précédent : 000D85; suivant : 000D87A 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
Affiliations:
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Le document en format XML
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Electronic address: triemen@gwdg.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Genetics and Physiopathology of Neurotransmission, Neurobiology Unit, CNRS, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France; Molecular Neurobiology of Behaviour, Johann-Friedrich-Blumenbach Institute, Georg-August-University of Goettingen, Schwann-Schleiden Research Center, Julia-Lermontowa Weg 3, 37077 Goettingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Issa, Abdul Raouf" sort="Issa, Abdul Raouf" uniqKey="Issa A" first="Abdul-Raouf" last="Issa">Abdul-Raouf Issa</name></author><author><name sortKey="Pech, Ulrike" sort="Pech, Ulrike" uniqKey="Pech U" first="Ulrike" last="Pech">Ulrike Pech</name></author><author><name sortKey="Coulom, Helene" sort="Coulom, Helene" uniqKey="Coulom H" first="Hélène" last="Coulom">Hélène Coulom</name></author><author><name sortKey="Nguy, M Van" sort="Nguy, M Van" uniqKey="Nguy M" first="M Vân" last="Nguy">M Vân Nguy</name></author><author><name sortKey="Cassar, Marlene" sort="Cassar, Marlene" uniqKey="Cassar M" first="Marlène" last="Cassar">Marlène Cassar</name></author><author><name sortKey="Jacquet, Melanie" sort="Jacquet, Melanie" uniqKey="Jacquet M" first="Mélanie" last="Jacquet">Mélanie Jacquet</name></author><author><name sortKey="Fiala, Andre" sort="Fiala, Andre" uniqKey="Fiala A" first="André" last="Fiala">André Fiala</name></author><author><name sortKey="Birman, Serge" sort="Birman, Serge" uniqKey="Birman S" first="Serge" last="Birman">Serge Birman</name></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Animals, Genetically Modified</term><term>Brain (metabolism)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Dopaminergic Neurons (metabolism)</term><term>Drosophila Proteins (metabolism)</term><term>Drosophila melanogaster (metabolism)</term><term>Female</term><term>Green Fluorescent Proteins (genetics)</term><term>Humans</term><term>Locomotion (genetics)</term><term>Locomotion (physiology)</term><term>Mushroom Bodies (innervation)</term><term>Oxidative Stress</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (physiopathology)</term><term>Reflex, Startle (genetics)</term><term>Reflex, Startle (physiology)</term><term>Signal Transduction</term><term>TRPC Cation Channels (metabolism)</term><term>alpha-Synuclein (biosynthesis)</term><term>alpha-Synuclein (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Green Fluorescent Proteins</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Drosophila Proteins</term><term>TRPC Cation Channels</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Locomotion</term><term>Reflex, Startle</term></keywords><keywords scheme="MESH" qualifier="innervation" xml:lang="en"><term>Mushroom Bodies</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Dopaminergic Neurons</term><term>Drosophila melanogaster</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Locomotion</term><term>Reflex, Startle</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Animals, Genetically Modified</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Oxidative Stress</term><term>Signal Transduction</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Basse-Saxe</li></region><settlement><li>Göttingen</li></settlement></list><tree><noCountry><name sortKey="Birman, Serge" sort="Birman, Serge" uniqKey="Birman S" first="Serge" last="Birman">Serge Birman</name><name sortKey="Cassar, Marlene" sort="Cassar, Marlene" uniqKey="Cassar M" first="Marlène" last="Cassar">Marlène Cassar</name><name sortKey="Coulom, Helene" sort="Coulom, Helene" uniqKey="Coulom H" first="Hélène" last="Coulom">Hélène Coulom</name><name sortKey="Fiala, Andre" sort="Fiala, Andre" uniqKey="Fiala A" first="André" last="Fiala">André Fiala</name><name sortKey="Issa, Abdul Raouf" sort="Issa, Abdul Raouf" uniqKey="Issa A" first="Abdul-Raouf" last="Issa">Abdul-Raouf Issa</name><name sortKey="Jacquet, Melanie" sort="Jacquet, Melanie" uniqKey="Jacquet M" first="Mélanie" last="Jacquet">Mélanie Jacquet</name><name sortKey="Nguy, M Van" sort="Nguy, M Van" uniqKey="Nguy M" first="M Vân" last="Nguy">M Vân Nguy</name><name sortKey="Pech, Ulrike" sort="Pech, Ulrike" uniqKey="Pech U" first="Ulrike" last="Pech">Ulrike Pech</name></noCountry><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Riemensperger, Thomas" sort="Riemensperger, Thomas" uniqKey="Riemensperger T" first="Thomas" last="Riemensperger">Thomas Riemensperger</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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