Linked Life Data

9757026

Source:http://linkedlifedata.com/resource/pubmed/id/9757026

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1998-12-10
pubmed:abstractText
Synapse loss in cerebral cortex and hippocampus is a prominent feature of Alzheimer's disease (AD) that is correlated with cognitive impairment. Postsynaptic regions of dendrites are subjected to particularly high levels of calcium influx and oxidative stress as a result of local activation of glutamate receptors, and are therefore likely to be sites at which neurodegenerative processes are initiated in AD. Data suggest that neurons may die in AD by a process called apoptosis which involves a stereotyped series of biochemical changes that culminate in nuclear fragmentation, and that amyloid beta-peptide (Abeta) may play a role in such apoptosis. We now report that Abeta induces apoptosis-related biochemical changes in cortical synaptosomes, and in dendrites of cultured hippocampal neurons. Exposure of synaptosomes to Abeta resulted in loss of membrane phospholipid asymmetry, caspase activation, and mitochondrial membrane depolarization. Cytosolic extracts from synaptosomes exposed to Abeta induced chromatin condensation and fragmentation in isolated nuclei indicating that signals capable of inducing nuclear apoptosis can be generated locally in synapses. Exposure of cultured hippocampal neurons to Abeta resulted in caspase activation and mitochondrial membrane depolarization in dendrites and cell bodies. A caspase inhibitor prevented Abeta-induced mitochondrial membrane depolarization in synaptosomes, and mitochondrial membrane depolarization and nuclear apoptosis in cultured hippocampal neurons. Collectively, the data demonstrate that apoptotic biochemical cascades can be activated in synapses and dendrites by Abeta, and suggest that such 'synaptic apoptosis' may contribute to synaptic dysfunction and degeneration in AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-8993
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Elsevier Science B.V.
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
807
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-76
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites.
pubmed:affiliation
Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, 211 Sanders-Brown Building, University of Kentucky, Lexington, KY 40536, USA. mmattson@aging.coa.uky.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.