# Role of age-accumulated circRNAs in long-term memory

> **NIH NIH R21** · UNIVERSITY OF NEVADA RENO · 2020 · $31,500

## Abstract

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.

## Key facts

- **NIH application ID:** 10019305
- **Project number:** 3R21AG058955-02S1
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Pedro Miura
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,500
- **Award type:** 3
- **Project period:** 2020-02-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019305

## Citation

> US National Institutes of Health, RePORTER application 10019305, Role of age-accumulated circRNAs in long-term memory (3R21AG058955-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019305. Licensed CC0.

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