# AGING AND CENTRAL CHOLINGERIC SYSTEMS

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 1991 · $170,011

## Abstract

Deficits in cholinergic function have been implicated in the loss of
ability to learn and remember which occurs in Alzheimer's Disease and to
some extent in normal aging.  Several reports have indicated that both
muscarinic and nicotinic receptors are affected as a function of aging and
in Alzheimer's Disease.  Several subtypes of both muscarinic and neuronal
nicotinic receptors have been cloned but drugs selective enough to
distinguish between the subtypes do not currently exist.  Thus, antibodies
with selectivity to each of the subtypes of muscarinic nicotinic receptors
have been generated utilizing fusion proteins corresponding to the unique
portions of each molecule.  We propose to utilize these antibodies:

1.  To examine the hypothesis that certain subtypes of muscarinic (m1-m5)
or neuronal nicotinic receptors are specifically affected in Alzheimer's
Disease.
2.  To determine the effects of normal aging on the density of each of the
subtypes of muscarinic and nicotinic receptors in human brain.
3.  To determine the effects of normal aging on the density of the subtypes
of muscarinic and nicotinic receptors in rat brain.  Additionally,
experiments will be conducted using biochemical (cyclic AMP accumulation or
phosphoinositide hydrolysis) and physiological assays (prolactin release)
to examine the hypothesis that these responses are blunted in aging due to
changes in specific receptors.
4.  To examine the hypothesis that in aged rats the observed large
differences from rat to rat in the ability to learn is mirrored by a loss
of a specific subtype(s) of muscarinic or nicotinic cholinergic receptor in
the hippocampus or cortex.  Thus, as rats age some will perform well on a
Morris swim maze and some will perform poorly.  In collaboration with Dr.
Michela Gallagher at the University of North Carolina, we will examine the
density of each subtype of muscarinic and nicotinic receptor in the brains
of aged (24-26 mo.) rats which have been tested behaviorally within one
week of euthanasia.  Preliminary data from Dr. Gallagher's laboratory
demonstrate a change in muscarinic receptors from hippocampus of aged rats
that show a learning deficit but not from aged rats that do not show a
deficit.

These experiments should provide important information about the precise
aspects of cholinergic receptors affected in aging and in AD and may
provide insight into potential therapeutic targets for e.g. Alzheimer's
Disease as well as other cognitive disorders.

## Key facts

- **NIH application ID:** 3121825
- **Project number:** 1R01AG009884-01
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **SAM.gov UEI:** TF2CMKY1HMX9
- **Principal Investigator:** BARRY B WOLFE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $170,011
- **Award type:** 1
- **Project period:** 1991-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121825

## Citation

> US National Institutes of Health, RePORTER application 3121825, AGING AND CENTRAL CHOLINGERIC SYSTEMS (1R01AG009884-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3121825. Licensed CC0.

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