Affordable Access

Oxidative stress and age-related neuronal deficits.

Authors
  • Joseph, J A
  • Denisova, N
  • Villalobos-Molina, R
  • Erat, S
  • Strain, J
Type
Published Article
Journal
Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid
Publication Date
Jan 01, 1996
Volume
28
Issue
1-3
Pages
35–40
Identifiers
PMID: 8871939
Source
Medline
License
Unknown

Abstract

Research from our laboratory has indicated that the loss of sensitivity that occurs in several receptor systems as a function of age may be an index of an increasing inability to respond to oxidative stress (OS). This loss occurs partially as a result of altered signal transduction (ST). Assessments have involved determining the nature of age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model, we have found that 1. Reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from striatal slices from both young and old animals could be restored with alpha-tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be induced with radiation exposure; and 4. Pre-incubation of the striatal slices with cholesterol decreased subsequent deleterious effects of NO or OH. on DA release. Thus, cholesterol, which increases in neuronal membranes as a function of age, may function as a potent antioxidant and protectant against neuronal damage. These results suggest that therapeutic efforts to restore cognitive deficits in aging and age-related disease might begin with antioxidant reversal of ST decrements.

Report this publication

Statistics

Seen <100 times