Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-10-22
pubmed:abstractText
Nerve growth factor regulates the developmental programmed cell death of certain neurons in the peripheral nervous system. The functions of nerve growth factor in the central nervous system are less well characterized. Nerve growth factor withdrawal results in the protein synthesis-dependent death of a large percentage of developing septal cholinergic neurons in sandwich tissue culture. In this study double labelling techniques were used to demonstrate that septal cholinergic neurons subjected to nerve growth factor withdrawal exhibit condensed chromatin and fragmented nuclei, and are labelled intensely for fragmented DNA. These degenerative changes are characteristic of apoptotic cell death. Half of the cholinergic neurons were committed to die and could no longer be rescued by nerve growth factor reapplication following approximately 16.5 h of nerve growth factor deprivation, whereas half of the cholinergic neurons could no longer be rescued by cycloheximide addition after only 9 h of nerve growth factor deprivation, suggesting that nerve growth factor and cycloheximide effect rescue by distinct mechanisms. Addition of a cyclic AMP analogue or depolarization with high K+, but not the general nuclease inhibitor aurintricarboxylic acid, prevented the death of cultured septal cholinergic neurons subjected to nerve growth factor withdrawal. Furthermore, these agents are capable of rescuing cholinergic neurons subjected to a period of nerve growth factor withdrawal after which addition of cycloheximide is no longer protective. Thus, nerve growth factor, cyclic AMP and high K+ can effect rescue after inhibition of translation ceases to be protective. These findings suggest that under defined conditions in vitro, withdrawal of nerve growth factor from septal cholinergic neurons during a critical period of development results in the apoptotic death of these CNS neurons, which can be prevented at the post-translational level by nerve growth factor, cyclic AMP and high K+.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-39
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Nerve growth factor withdrawal induces the apoptotic death of developing septal cholinergic neurons in vitro: protection by cyclic AMP analogue and high potassium.
pubmed:affiliation
Department of Anatomy, University of Cambridge, MRC Cambridge Centre for Brain Repair, U.K.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't