# GLUCOCORTICOIDS, STRESS, AND HIPPOCAMPAL AGING

> **NIH NIH R01** · MCGILL UNIVERSITY · 1993 · $79,502

## Abstract

One of the most intriguing features of brain aging is the tremendous
variability in the degree to which there is any loss of function. Certain
individuals function alertly and show no loss of intellectual ability even
into their 90's.  In contrast, as early as their mid-5O's, others show
memory disorders, language loss, disorientation, and in the extreme form,
develop clinical dementias, such as Alzheimer's diseasee. What are the
factors that might account for such impressive individual differences in
brain aging?

We are examining the way in which the hypothalamic-pituitary-adrenal (HPA)
axis might regulate how the brain ages.  There are at least two ways in
which this might occur: Increased exposure to adrenal glucocorticoids in
the aged rat might 1) accelerate or potentiate the loss of neurons and in
doing so increase the loss of cognitive function, or 2) decrease the
capacity of surviving cells to compensate for neuron loss, and this effect
also appears to involve a loss of function.  In these studies we are
attempting relate changes in HPA activity to individual differences in
hippocampal pathology in later life using animal models of both
"successful"(i.e. the absence of hippocampal pathology and cognitive
decline) and "unsuccessful" aging.  These experiments also involve long-
itudinal studies in order to determine the temporal relationship between
changes in HPA activity and hippocampal impairments.  Do changes in HPA
activity predict individual differences in the occurrence of hippocampal
degeneration? We are also examining the relationship between increased HPA
activity in later life and changes in other correlates of hippocampal
pathology (e.g., decreased glucose utilization, changes in NMDA receptor
bindin, neuron loss, changes in cholinergic systems,etc.).  Is there an
empirically valid profile of hippocampal decline and how is it related to
changes in HPA activity? Finall, we are examining whether increased
glucocorticoid levels in aged rats compromise function in the hippocampus
using the long-term potentiation model of synaptic plasticity. Is it
possible that increased glucocorticoid levels might not only potentiate the
loss of hippocampal neurons, but also compromise function in remaining
cells?

## Key facts

- **NIH application ID:** 3121354
- **Project number:** 5R01AG009488-03
- **Recipient organization:** MCGILL UNIVERSITY
- **SAM.gov UEI:** VJ62F6V2LE48
- **Principal Investigator:** Michael Joseph Meaney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $79,502
- **Award type:** 5
- **Project period:** 1991-04-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121354

## Citation

> US National Institutes of Health, RePORTER application 3121354, GLUCOCORTICOIDS, STRESS, AND HIPPOCAMPAL AGING (5R01AG009488-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121354. Licensed CC0.

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