Identifying sleep regulatory genes using a Drosophila model of insomnia. Export

@article{citeulike:4735974, 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.}, author = {Seugnet, L. and Suzuki, Y. and Thimgan, M. and Donlea, J. and Gimbel, S. I. and Gottschalk, L. and Duntley, S. P. and Shaw, P. J.}, citeulike-article-id = {4735974}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.5629-08.2009}, citeulike-linkout-1 = {http://www.jneurosci.org/cgi/content/abstract/29/22/7148}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19494137}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19494137}, day = {3}, doi = {10.1523/JNEUROSCI.5629-08.2009}, issn = {1529-2401}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, keywords = {f1000, sleep}, month = {June}, number = {22}, pages = {7148--7157}, posted-at = {2009-06-23 14:53:43}, priority = {2}, title = {Identifying sleep regulatory genes using a Drosophila model of insomnia.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.5629-08.2009}, volume = {29}, year = {2009} }

TY - JOUR ID - citeulike:4735974 L3 - citeulike-article-id:4735974 N2 - 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. IS - 22 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience SN - 1529-2401 EP - 7157 TI - Identifying sleep regulatory genes using a Drosophila model of insomnia. VL - 29 SP - 7148 KW - f1000 KW - sleep AU - Seugnet, L AU - Suzuki, Y AU - Thimgan, M AU - Donlea, J AU - Gimbel, SI AU - Gottschalk, L AU - Duntley, SP AU - Shaw, PJ PY - 2009/06/03/ UR - http://dx.doi.org/10.1523/JNEUROSCI.5629-08.2009 ER -