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

Dissel, S, Klose, M, Donlea, J, Cao, L, English, D, Winsky-Sommerer, Raphaelle-Valia, van Swinderen, B and Shaw, PJ (2016) Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease Neurobiology of Sleep and Circadian Rhythms, 2. pp. 15-26.

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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.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Dissel, SUNSPECIFIEDUNSPECIFIED
Klose, MUNSPECIFIEDUNSPECIFIED
Donlea, JUNSPECIFIEDUNSPECIFIED
Cao, LUNSPECIFIEDUNSPECIFIED
English, DUNSPECIFIEDUNSPECIFIED
Winsky-Sommerer, Raphaelle-ValiaR.Winsky-Sommerer@surrey.ac.ukUNSPECIFIED
van Swinderen, BUNSPECIFIEDUNSPECIFIED
Shaw, PJUNSPECIFIEDUNSPECIFIED
Date : 28 September 2016
Identification Number : 10.1016/j.nbscr.2016.09.001
Copyright Disclaimer : © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/cc-by-nc-nd/4.0/).
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 21 Sep 2016 12:46
Last Modified : 18 Aug 2017 14:42
URI: http://epubs.surrey.ac.uk/id/eprint/812268

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