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Interactions between diet and cognition

Award Number: R01DK123423
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Interactions between diet and cognition - Project Summary Consumption of an obesity-promoting “Western diet” (WD) is strongly associated with cognitive impairment and dementia risk, even independent of obesity 1-5. The hippocampus (HPC), a brain region classically associated with memory function and more recently with energy balance, is particularly vulnerable to the negative effects of WD consumption 4, 6. Emerging evidence from both humans and rodent models identifies the juvenile and adolescent stages as especially vulnerable developmental periods for WD-induced HPC dysfunction 5, 7-9. Our preliminary results presented herein reveal that juvenile and adolescent WD consumption is associated with long-lasting memory impairments and hyperphagia during adulthood. Remarkedly, these negative outcomes are present in the absence of obesity and persist despite a healthy diet intervention beginning at adult onset. This proposal will discover the biological mechanisms mediating early life WD-induced programming of disordered memory performance and eating behavior during adulthood. We recently discovered a functional link between early life sugar consumption, the gut microbiome, and HPC dysfunction 10. Applying an analogous approach with our novel early life WD model (sugar + saturated fat + processed foods), we have identified substantial gut microbiome changes in early life WD-fed vs. control rats, including alterations in bacterial populations that are correlated with HPC-dependent memory performance. The functional relevance of these results will be mechanistically evaluated in this proposal. Given that WD- induced microbiome changes are associated with changes in brain acetylcholine (ACh) signaling 11, and that HPC ACh signaling promotes memory function 12-18, additional experiments will explore our novel hypothesis that aberrant HPC ACh signaling is a neural basis for WD-associated HPC dysfunction. This hypothesis is supported by our preliminary results showing that early life WD yields long-lasting reductions in markers of ACh tone, and that nonspecific cholinergic receptor agonism reverses early life WD-associated HPC-dependent memory impairments. Proposed experiments utilize state-of-the-art in vivo imaging and pharmacological approaches to identify mechanisms linking early life WD consumption, HPC dysfunction, and ACh signaling. In addition to regulating memory function, the HPC has emerged as a key brain region in the higher- order control of food intake 6, 19. Our preliminary results show that early life WD consumption yields increased caloric intake driven by elevated meal size, an effect that persists even after a healthy diet intervention. Additional preliminary data reveal that HPC ACh binding dynamically increases throughout the course of a meal, and this effect is highly predictive of meal size. We will expand these results by evaluating how early life WD influences dynamic HPC ACh binding during meal consumption and sensitivity to various physiological satiation signals. Collective results from the proposal will identify novel neurobiological mechanisms through which the early life dietary environment programs for impaired cognition and altered energetic outcomes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $548,819 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	6	5/21/2025	NON-COMPETING CONTINUATION	$54,880
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	4/9/2025	NON-COMPETING CONTINUATION	$493,939
2025	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	2/13/2025	COMPETING CONTINUATION	$31,832
2025	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/13/2025	NON-COMPETING CONTINUATION	-$31,832
														Subtotal = $548,819

Issue Date FY: 2024 ( Subtotal = $502,968 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	2/5/2024	COMPETING CONTINUATION	$502,968
2024	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $502,968

Issue Date FY: 2022 ( Subtotal = $413,946 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/27/2022	NON-COMPETING CONTINUATION	$413,946
														Subtotal = $413,946

Issue Date FY: 2021 ( Subtotal = $429,329 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/14/2021	NON-COMPETING CONTINUATION	$429,329
														Subtotal = $429,329

Issue Date FY: 2020 ( Subtotal = $459,584 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/13/2020	NON-COMPETING CONTINUATION	$459,584
														Subtotal = $459,584

Issue Date FY: 2019 ( Subtotal = $482,161 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/18/2019	NEW	$482,161
														Subtotal = $482,161

Grand Total All Awards = $2,836,807

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Interactions between diet and cognition

Award Number: R01DK123423

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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