Functional Insight From Fruit Flies on Human ADHD Candidate Genes

Palle Duun Rohde, Ditte Demontis, Sandra Marie Neumann Arvidson, Lisbeth Strøm Madsen, Volker Loeschcke, Peter Sørensen, Anders Børglum, Torsten Nygaard Kristensen

Research output: Contribution to book/anthology/report/conference proceedingArticle in proceedingResearch

Abstract

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder emerging in early childhood with an average prevalence rate of 5% in children and 3.7% in adults. ADHD is characterized by inattention, impulsivity and hyperactivity. This, combined with educational and social dysfunctions, and increased risk of mental
comorbidities, makes ADHD a disorder with high individual and societal costs. We use Drosophila melanogaster as a model to investigate the phenotypic consequences of gene disruption of 14 genes with human orthologs,
selected by their proposed contribution to increased risk of developing ADHD. We use Minos mutants, where target genes have been disrupted by the Minos transposable element, to test the effect on locomotor activity.
By measuring the distance traveled, we find disparity in locomotor activity between control and Minos mutants. Impaired dopamine system underlies the majority of ADHD symptoms, and effective treatment is achieved with
amphetamines. We fed flies with either 1.5 mg/ml dexamphetamine dissolved in 5% w/w sucrose or a 5% w/w sucrose solution. Treatment with dexamphetamine increased activity of controls and some Minos lines, and decreased activity levels for other mutants. Decreased activity level, when treated with dexamphetamine, is seen when using other ADHD animal models. Our findings suggest involvement of the proposed candidate genes Genes, Brain, and Behavior 2015 36 Talk Abstracts in hyperactivity in D. melanogaster, providing functional evidence for their association with ADHD. Additional studies investigating conditional gene inactivation using UAS-GAL4 systems will further elucidate the importance of the investigated genes.
Original languageEnglish
Title of host publicationGenes, Brain, and Behavior 2015 : 17th Annual Meeting of the International Behavioural and Neural Genetics Society
Number of pages1
Place of PublicationUppsala
Publication date19 May 2015
Pages35
Publication statusPublished - 19 May 2015
Externally publishedYes
Event17th IBANGS Meeting 2015: The 17th Annual Genes, Brain & Behavior Meeting - Uppsala, Sweden
Duration: 19 May 201522 May 2015

Conference

Conference17th IBANGS Meeting 2015
Country/TerritorySweden
CityUppsala
Period19/05/201522/05/2015

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