# PROGRESSIVE CHOLINERGIC DYSFUNCTION IN AGING BRAIN

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 1993 · $127,940

## Abstract

Dysfunction of the cholinergic septo-hippocampal system is thought to be
a major factor underlying the memory loss and cognitive deficits
associated with aging.  The objective of this proposal is to clarify the
relationship between age-dependent loss or atrophy of cholinergic
neurons in the basal forebrain and the progression of age-related
impairments in hippocainpal information processing.  This objective will
be pursued in mature, middle-aged, and aged rats using neuroanatomical,
neurobehavioral, and neurophysiological techniques.  This proposal is
unique in correlating these multidisciplinary measures in individual
animals. These studies will characterize in detail the changes which
occur with normal aging in cholinergic neurons of the basal forebrain.
Progress along this line of research will provide the basis for
developing pharmacological strategies for the prevention and treatment
of age-related neurodegenerative disorders, such as Alzheimer's disease.

The specific aims of the research plan are:

1) To characterize age-dependent changes in the distribution and
morphology of cholinergic projection neurons in the brains of mature,
middle-aged, and aged rats.  This aim will be addressed by constructing
detailed cell maps of choline acetyltransferase (ChAT) immunoreactive
cells in the basal forebrain.

2) To relate the age-dependent changes in cholinergic projection neurons
determined in Specific Aim #1 to corresponding functional deficits in
behavioral tasks which require an intact septo-hippocampal cholinergic
system.  Animals which show age-dependent dysfunction will be examined
for specific patterns of atrophy in the basal forebrain cholinergic
system as determined in Specific Aim #1.

3) To utilize electrophysiological assessments of hippocampal cell
activity during continual tracking of delayed match-to-sample (DMTS) and
delayed nonmatch-to-sample (DNMTS) performance in aged rats as
signatures of age-dependent dysfunction of the septo-hippocampal
cholinergic projection system.

4) To retard or reverse age-dependent changes in functional, anatomical,
and electrophysiological indices of cholinergic system deterioration
through chronic administration of nerve growth factor (NGF).  This aim
will provide a critical test of the putative cholinergic mechanism of
NGF-induced facilitation of memory in aged rats.

## Key facts

- **NIH application ID:** 3122714
- **Project number:** 5R01AG010747-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **SAM.gov UEI:** H1HYA8Z1NTM5
- **Principal Investigator:** Rosemarie M Booze
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $127,940
- **Award type:** 5
- **Project period:** 1991-09-15 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122714

## Citation

> US National Institutes of Health, RePORTER application 3122714, PROGRESSIVE CHOLINERGIC DYSFUNCTION IN AGING BRAIN (5R01AG010747-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122714. Licensed CC0.

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