Sunday, June 1, 2025 6/1/2025

Diversity Supplement toTraffic-related air pollution exacerbates AD-relevant phenotypes in a genetically susceptible rat model via neuroinflammatory mechanism(s)

Award Number: R01AG074709
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Diversity Supplement toTraffic-related air pollution exacerbates AD-relevant phenotypes in a genetically susceptible rat model via neuroinflammatory mechanism(s) - Project Summary Epidemiological studies have reported a strong positive association between traffic-related air pollution (TRAP) and risk of neurodegenerative disease, including Alzheimer’s Disease (AD) and AD-related dementias (ADRD). Since human exposure to TRAP will continue to increase as a result of expanding global industrialization and urbanization, there is an urgent need to identify which components in TRAP endanger the human brain, and to identify how TRAP promotes neurodegenerative disease. The work described in this Diversity supplement will address these data gaps by leveraging a novel in vitro neuron-astrocyte-microglia triculture model that more faithfully recapitulates in vivo neuroinflammatory responses than standard neuron monocultures or neuron- astrocyte co-cultures to test the hypothesis that TRAP-derived fine particulate matter (PM2.5) interacts directly with microglia in the brain to promote AD-relevant pathology. The scientific premise for this hypothesis includes experimental evidence previously reported by our research team demonstrating that chronic exposure to ambient TRAP collected from a heavily-trafficked tunnel in Northern California and delivered unchanged in real-time to rats in an adjacent vivarium: (1) decreased the time-to onset and increased the magnitude of AD/ADRD-relevant phenotypes, including neuron cell loss in the entorhinal cortex and hippocampus; (2) TRAP promoted microglial activation, but had no effect on astrogliosis as determined by quantitative immunohistochemical analyses of IBA- 1/CD68 and GFAP expression; and (3) significantly increased the number of particles in the ultrafine PM size range present in the hippocampus of TRAP-exposed animals relative to filtered air controls. The research goals of this Diversity supplement are to (1) compare the neurotoxicity of TRAP-derived PM2.5 vs. TRAP-derived soluble gases in the triculture model; (2) determine whether microglia mediate the neurotoxic effects of TRAP- derived PM; and (3) assess the influence of sex and genotype on microglia response to TRAP. This research is complementary to and extends the research described in the parent grant, which is focused on examining the influence of chronic exposure to different sources of TRAP vehicular emissions on AD-relevant pathology in an animal model and examining the role of the lung-brain axis in mediating the effects of TRAP on the brain. The training goals of this Diversity supplement include: (1) develop the trainee’s knowledge and technical skill set to enable them to successfully conduct research on environmental influences on neurodegenerative disease; (2) guide the trainee’s research activity to ensure the generation of data needed to support their preparation of a competitive F31 application and advance to candidacy; (3) enhance the trainee’s professional skills; and (4) actively work with the trainee to build their professional networks to enhance their likelihood of transitioning to an independent career in academic research.


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 = $822,955 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Aging Research	001	3	3/26/2025	NON-COMPETING CONTINUATION	$684,780
2025	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Aging Research	002	2	5/5/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Aging Research	000	2	10/9/2024	EXTENSION WITH OR WITHOUT FUNDS	$138,175
														Subtotal = $822,955

Issue Date FY: 2024 ( Subtotal = $840,279 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Aging Research	001	2	7/25/2024	SUPPLEMENT FOR EXPANSION	$71,377
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Aging Research	000	2	5/3/2024	EXTENSION WITH OR WITHOUT FUNDS	$768,902
														Subtotal = $840,279

Grand Total All Awards = $1,663,234

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Diversity Supplement toTraffic-related air pollution exacerbates AD-relevant phenotypes in a genetically susceptible rat model via neuroinflammatory mechanism(s)

Award Number: R01AG074709

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer