Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease
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 disr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-01-01
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| Series: | Neurobiology of Sleep and Circadian Rhythms |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2451994416300153 |
| _version_ | 1819261646766342144 |
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| author | Stephane Dissel Markus Klose Jeff Donlea Lijuan Cao Denis English Raphaelle Winsky-Sommerer Bruno van Swinderen Paul J. Shaw |
| author_facet | Stephane Dissel Markus Klose Jeff Donlea Lijuan Cao Denis English Raphaelle Winsky-Sommerer Bruno van Swinderen Paul J. Shaw |
| author_sort | Stephane Dissel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T19:45:07Z |
| format | Article |
| id | doaj.art-675989bb79cb445db6e7636bbe1f4110 |
| institution | Directory Open Access Journal |
| issn | 2451-9944 |
| language | English |
| last_indexed | 2024-12-23T19:45:07Z |
| publishDate | 2017-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Sleep and Circadian Rhythms |
| spelling | doaj.art-675989bb79cb445db6e7636bbe1f41102022-12-21T17:33:33ZengElsevierNeurobiology of Sleep and Circadian Rhythms2451-99442017-01-0121526Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's diseaseStephane Dissel0Markus Klose1Jeff Donlea2Lijuan Cao3Denis English4Raphaelle Winsky-Sommerer5Bruno van Swinderen6Paul J. Shaw7Department of Neuroscience, Washington University, St. Louis, 660 S. Euclid Ave, St. Louis, MO, USADepartment of Neuroscience, Washington University, St. Louis, 660 S. Euclid Ave, St. Louis, MO, USADepartment of Neurobiology, University of California: Los Angeles, Los Angeles, CA, USADepartment of Neuroscience, Washington University, St. Louis, 660 S. Euclid Ave, St. Louis, MO, USADepartment of Neuroscience, Washington University, St. Louis, 660 S. Euclid Ave, St. Louis, MO, USASurrey Sleep Research Centre, Faculty of Health and Medical Sciences University of Surrey Guildford Surrey, GU2 7XH, United KingdomQueensland Brain Institute, The University of Queensland, Brisbane, Qld 4072, AustraliaDepartment of Neuroscience, Washington University, St. Louis, 660 S. Euclid Ave, St. Louis, MO, USA; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2451994416300153 |
| spellingShingle | Stephane Dissel Markus Klose Jeff Donlea Lijuan Cao Denis English Raphaelle Winsky-Sommerer Bruno van Swinderen Paul J. Shaw Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease Neurobiology of Sleep and Circadian Rhythms |
| title | Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease |
| title_full | Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease |
| title_fullStr | Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease |
| title_full_unstemmed | Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease |
| title_short | Enhanced sleep reverses memory deficits and underlying pathology in drosophila models of Alzheimer's disease |
| title_sort | enhanced sleep reverses memory deficits and underlying pathology in drosophila models of alzheimer s disease |
| url | http://www.sciencedirect.com/science/article/pii/S2451994416300153 |
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