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Int. J. Mol. Sci. 2018, 19(6), 1788; https://doi.org/10.3390/ijms19061788

Big Lessons from Tiny Flies: Drosophila melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

1
Institute of Pharmacology and the Gaston H. Glock Research Laboratories for Exploratory Drug Development, Center of Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
2
Department of Neurobiology, University of Vienna, A-1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Received: 22 May 2018 / Revised: 11 June 2018 / Accepted: 13 June 2018 / Published: 16 June 2018
(This article belongs to the Special Issue Drosophila Model and Human Disease)
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Abstract

The brain of Drosophila melanogaster is comprised of some 100,000 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g., motor activity, reward and aversion, memory formation, feeding, sexual appetite, etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference, etc. Flies harboring mutated human orthologs provide models which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput. View Full-Text
Keywords: Drosophila; dopamine; serotonin; neurodegeneration; neurotransmitter transporters; vesicular monoamine transporters Drosophila; dopamine; serotonin; neurodegeneration; neurotransmitter transporters; vesicular monoamine transporters
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Kasture, A.S.; Hummel, T.; Sucic, S.; Freissmuth, M. Big Lessons from Tiny Flies: Drosophila melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems. Int. J. Mol. Sci. 2018, 19, 1788.

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