Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease

Dissel, Stephane, Klose, Markus, Donlea, Jeff, Cao, Lijuan, English, Denis, Winsky-Sommerer, Raphaelle, van Swinderen, Bruno and Shaw, Paul J. (2017) Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease. Neurobiology of Sleep and Circadian Rhythms, 2 15-26. doi:10.1016/j.nbscr.2016.09.001


Author Dissel, Stephane
Klose, Markus
Donlea, Jeff
Cao, Lijuan
English, Denis
Winsky-Sommerer, Raphaelle
van Swinderen, Bruno
Shaw, Paul J.
Title Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease
Formatted title
Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease
Journal name Neurobiology of Sleep and Circadian Rhythms
ISSN 2451-9944
Publication date 2017-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.nbscr.2016.09.001
Open Access Status DOI
Volume 2
Start page 15
End page 26
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2018
Language eng
Formatted abstract
To test the hypothesis that sleep can reverse cognitive impairment during Alzheimer's disease, we enhanced sleep in flies either co-expressing human amyloid precursor protein and Beta-secretase (APP:BACE), or in flies expressing human tau. The ubiquitous expression of APP:BACE or human tau disrupted sleep. The sleep deficits could be reversed and sleep could be enhanced when flies were administered the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP). Expressing APP:BACE disrupted both Short-term memory (STM) and Long-term memory (LTM) as assessed using Aversive Phototaxic Suppression (APS) and courtship conditioning. Flies expressing APP:BACE also showed reduced levels of the synaptic protein discs large (DLG). Enhancing sleep in memory-impaired APP:BACE flies fully restored both STM and LTM and restored DLG levels. Sleep also restored STM to flies expressing human tau. Using live-brain imaging of individual clock neurons expressing both tau and the cAMP sensor Epac1-camps, we found that tau disrupted cAMP signaling. Importantly, enhancing sleep in flies expressing human tau restored proper cAMP signaling. Thus, we demonstrate that sleep can be used as a therapeutic to reverse deficits that accrue during the expression of toxic peptides associated with Alzheimer's disease.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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