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Role of age-accumulated circRNAs in long-term memory

Award Number: R21AG058955
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2023

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Role of age-accumulated circRNAs in long-term memory - Project Summary for Supplemental Activities ONLY Age-related cognitive declines are prominent features of normal aging. Understanding the molecular changes and how nervous system function is altered by the process of aging is important to understand loss of memory with age and in neurodegenerative diseases. As in humans, the nematode C. elegans experiences cognitive declines during aging, but the causes of these declines are not well-understood. One good indicator of age- related changes in neuronal function are the levels of the transcription factor CREB (cAMP responsible element binding protein). Preliminary work from our parent grant has shown that removing the age-accumulated circular RNA, circ-crh-1, derived from the host CREB results in C. elegans with a longer mean life-span, suggesting that circ-crh-1 accelerates normal aging. CircRNAs may have roles in healthy brain function, particularly learning and memory, due to their localization at synapses; however, their direct role in long-term memory has never been tested. Moreover, altered circRNA levels have been found to be associated with neurodegenerative diseases such as Alzheimer’s. In this administrative supplement for the U.S.-Japan BRCP collaborative research initiative, we propose to (1) test generated mutants of circRNAs including circ-crh-1 in long-term associative memory (LTAM), and (2) use our developed tools to profile genome-wide expression changes of circRNAs before and after LTAM training. Through these studies, the contributions of specific circRNAs and their global changes in functional cognition will be used to identify the best targets of therapeutic intervention to treat cognitive decline with age. Our proposal is a joint effort from UNR (Drs. Miura and Van Der Linden) with OIST (Dr. Maruyama) in Japan, and provides unique opportunities for the PIs to learn sophisticated methods in LTAM. In return, the PIs will provide instruction to trainees in the host lab on aging and circRNA profiling analysis. The proposal aligns naturally with NIA’s plan and will significantly advance work on the parent grant (R21AG058955) to create new knowledge on the role of individual circRNAs in age-related behaviors such as cognitive decline.


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: 2024 ( Subtotal = -$18,258 )
2024	2020	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Aging Research	000	2	1/11/2024	SUPPLEMENT FOR EXPANSION	-$18,258
														Subtotal = -$18,258

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	001	2	4/26/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2019	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	000	2	4/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	001	2	2/5/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2019	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	000	2	2/5/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $31,500 )
2020	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	000	2	4/6/2020	SUPPLEMENT FOR EXPANSION	$31,500
														Subtotal = $31,500

Issue Date FY: 2019 ( Subtotal = $179,012 )
2019	2019	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	000	2	5/30/2019	NON-COMPETING CONTINUATION	$179,012
														Subtotal = $179,012

Issue Date FY: 2018 ( Subtotal = $215,012 )
2018	2018	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Aging Research	000	1	9/5/2018	NEW	$215,012
														Subtotal = $215,012

Grand Total All Awards = $407,266

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Role of age-accumulated circRNAs in long-term memory

Award Number: R21AG058955

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2023

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