Investigating the impacts of pharmacological slow wave sleep enhancement on cognition and memory traces in an alzheimers disease model
Active Project Grant Awarded Last action
- Award ID
- F30AG084312
- Recipient
-
The Trustees Of Columbia University In The City Of New York UEI QHF5ZZ114M72
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $157,029
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 52% complete
- Place of performance
- New York, USA
Award details come from USAspending.gov.
Description
- Abstract
- Alzheimer's disease (ad), a debilitating neurodegenerative condition projected to affect over 150 million people by 2050, is associated with major disruptions in sleep. Sleep is an essential, ubiquitous process in all animals and is now recognized as a significant modulator of ad pathology. Recent literature indicate there is a particularly strong bidirectional relationship between loss of slow-wave sleep (SWS), the deepest sleep stage, and severity of ad. Additionally, studies enhancing slow-wave activity (SWA) in ad and other mouse models of neurodegeneration show improved pathology, suggesting this intervention has promising therapeutic potential. However, there is a GAP in knowledge of whether this SWA enhancement is capable of improving memory deficits in ad and/or normalize sleep-wake disturbances, which are emerging biomarkers of ad. Here, i will test the hypothesis that pharmacological SWA enhancement in the APP/PS1 mouse of model of ad normalizes sleep-wake rhythms, decreases plaque burden, and improves memory performance by altering neural ensembles underlying memory. I will use a comparative approach to test the efficacy of two compounds, gaboxadol, a selective gabaa agonist, and trazadone, an FDA approved atypical antidepressant, that have been well-characterized for their SWA-enhancing effects. In aim 1A, i will use in vivo microdialysis and piezosleep recordings to investigate if administration of gaboxadol or trazadone to APP/PS1 mice normalizes characteristic sleep-wake disruptions in activity and interstitial a rhythms. In aim 1B, i will use electroencephalography (EEG) recordings to investigate if chronic administration of either drug to APP/PS1 mice improves associated disruptions to sleep architecture. I will additionally assess for decreases in plaque burden after both of these experiments. In aim 2, i will investigate if SWA enhancement with either drug is able to improve memory performance, and if this is mediated by systems-level alterations in memory traces, the proposed biological substrates underlying memory encoding, storage, and retrieval. I will use a custom brain wide mapping pipeline to investigate how memory traces are altered in the hippocampus (HPC), and additional relevant regions such as the amygdala (AMY), nucleus reuniens (NE), and retrosplenial cortex (RSC). Successful completion of this project will critically inform our understanding of the therapeutic potential of pharmacological SWA enhancement as a treatment strategy in ad. IT will further elucidate the regional and network-level changes that may mediate its effects. The research and scientific expertise additionally developed through this kirschstein-nrsa F30 fellowship award will support my long-term goal of becoming an independent physician-scientist.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $55,114 | |
| Amendment | $51,501 | |
| Original award | $50,414 |
Quick answers
Who received award F30AG084312?
F30AG084312 was awarded to The Trustees Of Columbia University In The City Of New York by National Institute on Aging (National Institutes of Health) on January 3, 2025.
How much is award F30AG084312 worth?
$157,029 has been obligated on F30AG084312.
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