# MECHANISMS OF AGING AT THE NEUROMUSCULAR JUNCTION

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1989 · $204,384

## Abstract

The neuromuscular junction (NMJ) serves as a model in the analysis of
aglng of synapses. We propose to evaluate the mechanisms of two improtant
age changes at the NMJ - altered transmitter release and increased
outgrowth and retraction of motor nerve terminals.

Indirect data indicate that the alteration in synaptic transmission in
aging NMJ is due to altered nerve terminal depolarization or calcium
influx. Because mamalian motor nerve terminals are too small for
intracellular recording, these two key parameters of synaptic efficacy
will be evaluated with new voltage- or calcium-sensitive fluorescent
dyes. With additional electrophysiologic techniques, the ion channel
properties of synaptic terminals will be determined as a function of age
and directly related ion channel properties of synaptic terminals will be
determined as a function of age and directly related to altered
transmitter release in individual identified junctions. By comparing
muscles in which there is age related increase, decrease, or unchanged
transmitter release in individual identified junctions. By comparing
muscles in which there is age-related increase, decrease, or unchanged
transmitter release, physiologically relevant age changes can be
separated from those that do not correlate with altered transmitter
release. Also age changes in propogation or wave-form of depolarization
and those involving calcium channels can be distinguished. This new
approach will also shed light on synaptic function in young animals.

Two hypotheses will be tested which account for the morphologic
remodelling of NMJ in aging mice. The first is that adhesion of nerve
terminal to synaptic matrix is reduced, allowing nerve terminal
outgrowth. The following predictions will be tested with
immunocytochemical and tissue culture techniques; 1. During regeneration
in vivo or outgrowth of ciliary ganglion cells on cryostat sections in
vitro, preferential adhesion to synaptic sites will be diminished in old
muscle; 2. Intrinsic neuronal or extrinsic matrix components related to
adhesion will be reduced with age; and 3. Outgrowth sites of nerve
terminals will be associated with reduced density of adhesive components.
A second hdypotheseis is that nerve terminal remodelling in old mice
results form diminution of supply or detabolism and removal of membrane
components. Microimmunocuytochemical methods have been devised to compare
amounts of transported material individual motor nerves. These studies
will elucidate mechanisms of morphologic instabilty of aging synapses.

## Key facts

- **NIH application ID:** 3120684
- **Project number:** 1R01AG008886-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** NORMAN ROBBINS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $204,384
- **Award type:** 1
- **Project period:** 1989-05-02 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120684

## Citation

> US National Institutes of Health, RePORTER application 3120684, MECHANISMS OF AGING AT THE NEUROMUSCULAR JUNCTION (1R01AG008886-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120684. Licensed CC0.

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