Abstract

Although it is widely accepted that sleep must serve an essential biological function, little is known about molecules that underlie sleep regulation. Given that insomnia is a common sleep disorder that disrupts the ability to initiate and maintain restorative sleep, a better understanding of its molecular underpinning may provide crucial insights into sleep regulatory processes. Thus, we created a line of flies using laboratory selection that share traits with human insomnia. After 60 generations, insomnia-like (ins-l) flies sleep 60 min a day, exhibit difficulty initiating sleep, difficulty maintaining sleep, and show evidence of daytime cognitive impairment. ins-l flies are also hyperactive and hyperresponsive to environmental perturbations. In addition, they have difficulty maintaining their balance, have elevated levels of dopamine, are short-lived, and show increased levels of triglycerides, cholesterol, and free fatty acids. Although their core molecular clock remains intact, ins-l flies lose their ability to sleep when placed into constant darkness. Whole-genome profiling identified genes that are modified in ins-l flies. Among those differentially expressed transcripts, genes involved in metabolism, neuronal activity, and sensory perception constituted over-represented categories. We demonstrate that two of these genes are upregulated in human subjects after acute sleep deprivation. Together, these data indicate that the ins-l flies are a useful tool that can be used to identify molecules important for sleep regulation and may provide insights into both the causes and long-term consequences of insomnia.

Department(s)

Biological Sciences

Keywords and Phrases

4 Aminobutyric Acid; 4 Aminobutyric Acid A Receptor; Cholesterol; Dopamine; Fatty Acid; Filamin A; Malate Dehydrogenase (Decarboxylating); Serotonin; Triacylglycerol, 4 Aminobutyric Acid Brain Level; Animal Experiment; Animal Model; Arousal; Article; Cognitive Defect; Controlled Study; Darkness; Dopamine Brain Level; Drosophila; Female; Gene Expression Profiling; Gene Identification; Human; Hyperactivity; Insomnia; Learning; Locomotion; Male; Molecular Clock; Nerve Cell; Nonhuman; Normal Human; Priority Journal; Serotonin Brain Level; Sleep; Sleep Deprivation; Vision, Analysis Of Variance; Animals; Animals, Genetically Modified; Avoidance Learning; Basic Helix-Loop-Helix Transcription Factors; Behavior, Animal; Cholesterol; Circadian Rhythm; Contractile Proteins; Disease Models, Animal; Dopamine; Drosophila; Drosophila Proteins; Fatty Acids, Nonesterified; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Lipids; Locomotion; Malate Dehydrogenase; Male; Microfilament Proteins; Neurotransmitter Agents; Oligonucleotide Array Sequence Analysis; Peptide Hormones; Phenotype; Sleep; Sleep Deprivation; Sleep Initiation And Maintenance Disorders; Statistics, Nonparametric; Stress, Psychological; Triglycerides; Wakefulness

International Standard Serial Number (ISSN)

1529-2401

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2009 L. Seugnet et. al., All rights reserved.

PubMed ID

19494137

Included in

Biology Commons

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