# NEUROPATHOLOGY OF THE AGING SYMPATHETIC NERVOUS SYSTEM

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1992 · $207,153

## Abstract

Dysfunction of the aged human autonomic nervous system is an increasingly
recognized, but poorly understood, clinical problem, the pathologic basis
of which is largely unknown.  Our initial studies of aging human
sympathetic ganglia have demonstrated:  i) neuroaxonal dystrophy comparable
to that we have characterized in aged experimental animals; ii)
preferential damage of prevertebral versus paravertebral sympathetic
ganglia; iii) an age-related increase in the number of dystrophic axons;
and, iv) selective involvement of NPY containing nerve terminals.  The
studies proposed in this research plan represent a significant expansion of
our initial investigation of aging human sympathetic ganglia to precisely
characterize the pathologic effects of age on the human sympathetic nervous
system, to integrate these findings with animal models of aging, and
ultimately to define the pathogenesis of autonomic dysfunction in aging.

We will characterize neuroaxonal dystrophy in human ganglia and determine
if it is associated with a particular clinical entity or presentation.
Other studies will investigate the dendritic structure of aging principal
sympathetic neurons and identify the origin of dystrophic nerve terminals
using intraneuronal labeling and lipophilic dyes (di-I) in both animal and
human ganglia.  In an attempt to identify the earliest alterations in human
dystrophic axons we will use immunoelectron microscopy to concentrate on
NPY containing nerve terminals, which are selectively targeted in human
aging.  RIAs will be used to quantitate the ganglionic content of NPY as a
measure of the severity of the axonopathy.  Finally, we will test the
proposed hypothesis that abnormal neurofilament metabolism underlies the
development of dystrophic axons in aging human sympathetic ganglia.
Specifically, e will:  test for unusual forms of ganglionic neurofilament
proteins by SDS-PAGE with Western blotting; immunohistochemically probe for
abnormally distributed neurofilament proteins and assay enzymes responsible
for neurofilament degradation (calpains); and, finally, attempt to mimic
the axonopathy in the sympathetic ganglia of young animals using local
application of calpain inhibitors in vivo.  Overall, this research proposal
represents a multi-faceted investigation into the effects of age on the
sympathetic nervous system.  Minimally, these investigations will yield a
wealth of data on aging human sympathetic ganglia and may provide clues to
the pathogenesis (and possible treatment) of autonomic dysfunction in aged
humans.

## Key facts

- **NIH application ID:** 3122284
- **Project number:** 1R01AG010299-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** ROBERT EDWARD SCHMIDT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $207,153
- **Award type:** 1
- **Project period:** 1992-05-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122284

## Citation

> US National Institutes of Health, RePORTER application 3122284, NEUROPATHOLOGY OF THE AGING SYMPATHETIC NERVOUS SYSTEM (1R01AG010299-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122284. Licensed CC0.

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