# DEGENERATION, REPAIR AND AGING IN THE CNS

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1993 · $192,745

## Abstract

The research proposed in this application is intended to examine the
effects of age on plasticity and repair in the damaged dopamine (DA)
system.  The primary model to be used in this research is the
MPTP-treated mouse.  A comparative analysis of the effects of GM1
ganglioside and putative DAergic neurotrophic factors in young mice with
and without significant substantia nigra (SN) DA cell loss and in aged
mice with significant SN cell loss will be performed.  These studies will
provide information concerning the ability of trophic factors to
stimulate recovery in the DA system under different lesion conditions and
to assess the effect of age on the trophic response.  The specific aims
of the proposed research are to: 1)compare the effects of GM1
ganglioside, bFGF, IFG-I, BDNF and EGF and the effects of GM1 alone and
in combination with the above-mentioned trophic factors in young mice
with different degrees of MPTP-induced damage and in aged mice.  These
studies will assess in vivo regenerative capacity and response of the DA
system to trophic influences under the conditions mentioned above; 2)
examine possible mechanisms responsible for increases in striatal DA in
young MPTP-lesioned mice and in medial forebrain bundle transected rats,
and; 3) examine possible mechanisms contributing to age-related decline
in GMl effectiveness.  Mechanistic issues will be addressed with in vivo
studies and more directly by studying GM1 and trophic factor effects on
cultured DA neurons exposed to the toxin MPP+.  These studies will
specifically examine the extent to which GM1-induced recovery in the DA
system is due to a biochemical up-regulation of remaining DA neurons
and/or a sprouting response.  DA turnover, DA uptake, tyrosine
hydroxylase (TH) and GAP-43 immunohistochemistry and TH, GAP-43, and
tubulin in situ hybridization will be studied in vivo and in vitro.
These studies, should provide basic information concerning the effects of
GM1 and other trophic agents on the damaged DA system in young and aged
animals and provide further insight into basic mechanisms of these
responses.  This work might have potential clinical significance for the
future treatment of degenerative CNS disorders and particularly disorders
such as Parkinson's disease which are associated with aging.

## Key facts

- **NIH application ID:** 3122254
- **Project number:** 5R01AG010280-02
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** JAY S SCHNEIDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $192,745
- **Award type:** 5
- **Project period:** 1992-09-30 → 1995-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122254

## Citation

> US National Institutes of Health, RePORTER application 3122254, DEGENERATION, REPAIR AND AGING IN THE CNS (5R01AG010280-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122254. Licensed CC0.

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