Source:http://linkedlifedata.com/resource/pubmed/id/19100287
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2009-1-26
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholinesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Atropine,
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Reactivators,
http://linkedlifedata.com/resource/pubmed/chemical/HI 6,
http://linkedlifedata.com/resource/pubmed/chemical/Oximes,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridinium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Soman,
http://linkedlifedata.com/resource/pubmed/chemical/olanzapine
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0161-813X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
72-80
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19100287-Acetylcholine,
pubmed-meshheading:19100287-Acetylcholinesterase,
pubmed-meshheading:19100287-Animals,
pubmed-meshheading:19100287-Atropine,
pubmed-meshheading:19100287-Benzodiazepines,
pubmed-meshheading:19100287-Cholinesterase Reactivators,
pubmed-meshheading:19100287-Corpus Striatum,
pubmed-meshheading:19100287-Hippocampus,
pubmed-meshheading:19100287-Male,
pubmed-meshheading:19100287-Maze Learning,
pubmed-meshheading:19100287-Neurogenesis,
pubmed-meshheading:19100287-Oximes,
pubmed-meshheading:19100287-Pyridinium Compounds,
pubmed-meshheading:19100287-Rats,
pubmed-meshheading:19100287-Rats, Sprague-Dawley,
pubmed-meshheading:19100287-Seizures,
pubmed-meshheading:19100287-Soman
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pubmed:year |
2009
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pubmed:articleTitle |
Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning.
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pubmed:affiliation |
TNO Defence, Security and Safety, BU Biological and Chemical Protection, Rijswijk, The Netherlands. marloes.joosen@tno.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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