# The Role of Oligodendrocytes in Cognitive Decline after Alcohol and Aging

> **NIH NIH R21** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2024 · $227,335

## Abstract

PROJECT SUMMARY
Cognition declines with age, and severe and prolonged use of alcohol (alcohol use disorder, AUD) could be
accelerating and worsening these aging processes. The timing and magnitude of cognitive dysfunction
correlates with the emergence of white matter loss in frontal and temporal lobes (frontotemporal intercortical
myelinated axons), suggesting that myelin deficits may underlie these cognitive changes. However, the
direct functional contribution these brain changes may (or may not) have on reduced cognitive abilities after
alcohol in aged individuals is unknown, as are the underlying mechanisms. Thus, more direct empirical
testing is greatly needed. The experiments of this proposal are designed to probe the mechanistic overlap
of AUD and aging on white matter tracks by drilling down specifically on mechanisms involving myelinating
cells of the central nervous system (oligodendrocytes, OLs). We use transgenic technology and cell fate
mapping to track the birth and development of oligodendroglial populations involved in myelinating
frontotemporal axons to learn about the cellular processes that lead to impaired remyelination capacity after
alcohol exposure in older mice. We posit that in aged animals, alcohol induces delays in OL differentiation
that prevents proper myelin ensheathment of intracortical axons and advances cognitive decline. Our
experimental design tackles these research questions with precision, scaling from molecular—to
phenotypic—to behavior. Manipulating these cellular processes allows for testing the direct link between
myelin formation and cognitive functioning. Our comprehensive assessment of cognitive abilities as a
function of age and sex also fills a critical gap by dissecting differential sensitivities that are clinically
important for consideration. These essential first steps provide a solid foundation for a larger project on
aging and alcohol interactions and whether reversal is possible with therapeutic targeting of cellular
development in humans, opening new avenues for discovery of treatment strategies for alcohol and age-
related cognitive dysfunction and dementia.

## Key facts

- **NIH application ID:** 10896500
- **Project number:** 1R21AA031376-01A1
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Heather Noël Richardson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $227,335
- **Award type:** 1
- **Project period:** 2024-05-10 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896500

## Citation

> US National Institutes of Health, RePORTER application 10896500, The Role of Oligodendrocytes in Cognitive Decline after Alcohol and Aging (1R21AA031376-01A1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10896500. Licensed CC0.

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