# MODEL OF DEMENTIA--SENESCENCE ACCELERATED

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 1993 · $130,608

## Abstract

There is no satisfactory treatment available to prevent, delay   or
reverse the geriatric learning and memory dysfunction which is the
hallmark of age-related dementia. The proposed research will evaluate
whether the Senescence Accelerated Mouse (SAM P/8) is a useful model to
study age-related changes in learning and memory.  The SAM P/8 strain has
a 37% increase in the rate of aging  beyond maturation but develops
learning dysfunction at twice the rate of mice with normal life spans
such as its geneticcounteer part the SAM R/1 or the C57BL/6Nnia strains.
Preliminary data indicates that CAT activity shows an age-related
decrease cholinomimetic administration will only enhance retention in
older SAM mice if the dose is increased above that needed to enhance
retention in age-matched controls having a normal life span.  We will
examine the ability of the SAM P/8 mice to learn and remember aversive
and appetitive tasks of varying degrees of complexity.  The ability of
the SAM P/8 mice to learn and remember will be compared to its genetic
control, SAM R/1, which does not show accelerated aging and the
C57BL/6Nnia mouse strain which is the most widely used strain of mice in
aging studies.  SAM P/8 mice show an age dependent increase in granules
in the hippocampus which react positively to period acid Schiff's
reaction (PAS).  These PAS-positive granules appear at a much early age
in SAM P/8 mice than in the SAM R/1 or C57BL strains.  We will examine
more closely the age-related increase in PAS-positive staining granules
in the hippocampus of SAM P/8 mice to learning and memory dysfunction and
changes in hippocampus neurotransmitter activity.  We will relate the
alterations in learning and memory dysfunction to changes in pre- and
post-synaptic markers for four neurotransmitter systems which are
particularly important for memory processing in the hippocampus (i.e.,
cholinergic, GABAergic, glutaminergic and noradrenergic).   We will
examine the ability of pharmacological manipulations of these
neurotransmitters systems to alleviate memory dysfunction may be the
cause of an age-related impairment of learning and memory in SAM P/8
mice, studies of the other major transmitters of the hippocampus known
to be involved in memory processing is needed to determine whether a
general decline in neurotransmitter function occurs with age or whether
it is specific to the cholinergic system.  These experiments should allow
us to determine which neurotransmitter(s) is responsible for the learning
and memory dysfunction in SAM P/8 mice.

## Key facts

- **NIH application ID:** 3121170
- **Project number:** 5R01AG009321-03
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **SAM.gov UEI:** JNBLLTBTLLD8
- **Principal Investigator:** JAMES F FLOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $130,608
- **Award type:** 5
- **Project period:** 1991-06-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121170

## Citation

> US National Institutes of Health, RePORTER application 3121170, MODEL OF DEMENTIA--SENESCENCE ACCELERATED (5R01AG009321-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121170. Licensed CC0.

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