Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.
OBJECTIVE
Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on shortterm memory using a Drosophila model of Parkinson disease.


METHODS
Transgenic strains of Drosophila melanogaster.


METHODS
Using the GAL4-UAS system, human alpha-synuclein was expressed throughout the nervous system of adult flies. Alpha-synuclein expressing flies (alpha S flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. MEASURMENTS AND RESULTS: When sleep deprived at an intermediate stage of the pathology, alpha S flies showed persistent short-term memory deficits that lasted > or = 3 days. Cognitive deficits were not observed in younger alpha S flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived alpha S flies. Blocking D1-like receptors during sleep deprivation prevented persistent shortterm memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits.


CONCLUSIONS
These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.
Seugnet
Laurent
L
Washington University School of Medicine, St. Louis, MO 63110, USA.
Galvin
James E
JE
Suzuki
Yasuko
Y
Gottschalk
Laura
L
Shaw
Paul J
PJ
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D001362:Avoidance Learning; D002755:Choice Behavior / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D007266:Inhibition, Psychological; D008027:Light; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D009042:Motivation; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D016627:Oxidopamine / Q000037:antagonists & inhibitors; D020734:Parkinsonian Disorders / Q000235:genetics / Q000523:psychology*; D012333:RNA, Messenger / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012892:Sleep Deprivation / Q000523:psychology*; D051844:alpha-Synuclein / Q000235:genetics
C093147:Dop1R1 protein, Drosophila; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D051844:alpha-Synuclein; D016627:Oxidopamine; D003474:Curcumin