# The role of proopiomelanocortin neurons in age-related cognitive decline

> **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $282,524

## Abstract

Cognitive decline is a common sequela of mammalian aging, from rodents to humans. As it often results in
the inability to live independently, slowing or preventing the loss of cognition with age would significantly
increase the quality of life for older adults. While the etiology of age-related cognitive impairment is unknown,
there is increasing evidence that age-related changes in neurotransmitters may play an important role.
Neurotransmitters produced from proopiomelanocortin (POMC) are of particular interest because they
modulate cognition, metabolic rate and other age-related phenotypes, and their levels are known to decrease
with age. Furthermore, when administered systemically, or into the brain, they improve memory, attention, and
cognition and delay the decline in cognition in mouse models of Alzheimer’s disease. However, which POMC-
producing neurons are responsible for the age-related decline in brain POMC, the mechanism by which this
occurs, and its contribution to age-dependent cognitive decline are not known. Our studies will yield insight into
mechanisms responsible for age-related changes in POMCHipp neurons and reveal whether interventions that
delay aging act, in part, by modulating these neurons. Filling these gaps in knowledge is essential f or
development of interventions to reverse cognitive aging. The proposed work is enabled by a novel combination
of technology including retrograde labeling of POMCHipp neurons and mouse genetic models that together allow
us to specifically target these neurons. This will allow us to analyze age-dependent changes in the number and
projection density (Aim 1) and gene expression (Aim 2) of POMCHipp neurons that may provide insight into the
decline in cognition with age. We will further determine whether these changes can be reversed by treatment
with rapamycin, a drug that increases lifespan in mice while ameliorating age-related declines in cognition, as
well the age-related dysfuncton of Arc POMCPVN neurons. Finally, in Aim 3 we will specifically activate or inhibit
the function of Arc POMCHipp neurons and measure the impact on cognition. Our approach is highly innovative
and will define the role POMCHipp neurons in the mechanisms responsible for cognitive decline with age, and
provide a framework for studies to develop interventions to reduce age-related cognitive decline. This JPI
project will provide the preliminary data, mentorship, and resources for the development of a competitive,
independent research grant proposal in the field of geroscience.

## Key facts

- **NIH application ID:** 10077917
- **Project number:** 5P20GM125528-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** AMANDA L SHARPE
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $282,524
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077917

## Citation

> US National Institutes of Health, RePORTER application 10077917, The role of proopiomelanocortin neurons in age-related cognitive decline (5P20GM125528-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077917. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*