Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1996-8-19
pubmed:abstractText
Although there are numerous findings which suggest that the pathogenesis of age-related neurodegenerative disorders (e.g., AD and PD) may involve oxidative stress (OS), relationships between functional age-related neuronal deficits, especially those with behavioral correlates, and OS have been difficult to establish. We have attempted to establish such relationships by determining the role of OS in the loss of muscarinic receptor (mAChR) sensitivity in aging. These decrements are expressed as age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model we have found that: a) The reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); b) Striatal slices from old animals showed increased sensitivity (e.g., reduced DA release or oxo-enhancement of K(+)-ERDA) to the in vitro application of sodium nitroprusside, a potent NO generator or to H2O2 which treatment of striatal slices from young animals with these agents or exposure of young animals to low doses of whole-body 56Fe irradiation decreased mAChR sensitivity and signal transduction (ST). Protection from the NO- or H2O2-induced deficits could be prevented with Trolox, PBN or cholesterol pretreatment. Evidence derived from PC-12 cells suggests that OS may directly affect ST by decreasing Ca2+ flux and increasing the length of the recovery period (i.e., return to baseline Ca2+ levels) after KCI (30 mM) depolarization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
786
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
112-9
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Increased sensitivity to oxidative stress and the loss of muscarinic receptor responsiveness in senescence.
pubmed:affiliation
USDA-ARS Human Nutrition Research Center, Boston, Massachusetts 02111, USA.
pubmed:publicationType
Journal Article, Review