Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-1-26
pubmed:abstractText
To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and the oxime HI-6 for reactivation of soman-inhibited acetylcholinesterase. We also investigated whether sub-chronic treatment with the reported neurogenesis enhancer olanzapine would stimulate neurogenesis and possibly normalize the anticipated long-term deleterious effects of soman intoxication. Animals were treated with HI-6 (125 mg/kg i.p.), followed after 30 min by soman (200 microg/kg s.c.) and atropine sulphate (16 mg/kg i.m.) 1 min thereafter. Soman poisoning led to an elevation of extracellular acetylcholine levels to 1500% over baseline values as assessed by striatal microdialysis. Brain acetylcholinesterase was inhibited over 95%. This was accompanied by short recurrent seizures lasting for 40 min. Osmotic minipumps releasing olanzapine (7.5 mg/kg/day) or vehicle were subcutaneously implanted 24 h post-intoxication. After drug delivery for 4 weeks, newborn cells were BrdU labeled. Learning and memory performance were assessed 8 weeks after soman poisoning, followed by analysis of surviving newborn cells (BrdU) and neurogenesis (doublecortin, DCX). Eight weeks after soman-intoxication a significantly impaired learning ability was found that was paralleled by significantly lower numbers of DCX-positive cells but no changes in the number of BrdU-labeled cells. Apparently, the present Olanzapine regime was ineffective. We conclude that soman poisoning has long lasting effects on learning ability, a finding that was accompanied by impaired neurogenesis. Although we confirm a correlation between impaired neurogenesis and cognitive deficits, establishing the true causal relationship between these processes in OP exposed animals awaits future research.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0161-813X
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
72-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning.
pubmed:affiliation
TNO Defence, Security and Safety, BU Biological and Chemical Protection, Rijswijk, The Netherlands. marloes.joosen@tno.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't