Identifying Sleep Regulatory Genes Using aDrosophilaModel of Insomnia
2800 Neuroscience
Dopamine
Filamins
612
Fatty Acids, Nonesterified
Animals, Genetically Modified
03 medical and health sciences
Contractile Proteins
0302 clinical medicine
Avoidance Learning
Basic Helix-Loop-Helix Transcription Factors
Animals
Drosophila Proteins
Humans
Analysis of Variance
Behavior, Animal
Gene Expression Profiling
Lipids
Circadian Rhythm
Disease Models, Animal
Cholesterol
Gene Expression Regulation
Drosophila
Female
DOI:
10.1523/jneurosci.5629-08.2009
Publication Date:
2009-06-03T17:37:34Z
AUTHORS (8)
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-lflies 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-lflies lose their ability to sleep when placed into constant darkness. Whole-genome profiling identified genes that are modified inins-lflies. 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 theins-lflies 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.
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