Rotenone induces non-specific central nervous system and systemic toxicity.
Identifieur interne : 002B62 ( Main/Exploration ); précédent : 002B61; suivant : 002B63Rotenone induces non-specific central nervous system and systemic toxicity.
Auteurs : Nicolas Lapointe [Canada] ; Michel St-Hilaire ; Maria-Grazia Martinoli ; Julie Blanchet ; Peter Gould ; Claude Rouillard ; Francesca CicchettiSource :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2004.
English descriptors
- KwdEn :
- Animals, Brain (drug effects), Brain (pathology), Disease Models, Animal, Dopamine (metabolism), Motor Activity (drug effects), Neurodegenerative Diseases (chemically induced), Neurodegenerative Diseases (pathology), Neurodegenerative Diseases (physiopathology), Neurons (drug effects), Neurons (pathology), Parkinson Disease, Secondary (chemically induced), Rats, Rotenone (toxicity).
- MESH :
- chemical , metabolism : Dopamine.
- chemically induced : Neurodegenerative Diseases, Parkinson Disease, Secondary.
- drug effects : Brain, Motor Activity, Neurons.
- pathology : Brain, Neurodegenerative Diseases, Neurons.
- physiopathology : Neurodegenerative Diseases.
- chemical , toxicity : Rotenone.
- Animals, Disease Models, Animal, Rats.
Abstract
We investigated the dopaminergic (DA) neuronal degeneration in animals subjected to systemic treatment of rotenone via subcutaneous delivery. Behavioral observations revealed a hypokinetic period in rats sacrificed at 3 and 5 days, and dystonic episodes in animals sacrificed at 8 days. Less than 20% of the total number of animals given rotenone depicted brain lesions after 8 days of treatment, as demonstrated by a significant loss of DA fibers in the striatum, but not of DA nigral neurons. Tyrosine hydroxylase-negative striatal territories were characterized by post-synaptic toxicity as demonstrated by a decreased number of interneurons labeled for choline acetyltransferase, NADPH-diaphorase, parvalbumin, and projection neurons labeled for calbindin and nerve growth factor inducible-B (NGFI-B). Post-synaptic neurodegeneration was demonstrated further by abundant striatal staining for Fluoro-Jade. Decrease in the nuclear orphan receptor Nurr1 expression was the only significant change observed at the level of the substantia nigra. Autopsy reports confirmed that animals suffered from severe digestion problems. These data suggest that hypokinesia observed between 3 and 5 days is the result of general health problems rather than a specific motor deficit associated to Parkinson's disease (PD) symptoms. Overall, the effects of rotenone toxicity are widespread, and subcutaneous administration of this toxin does not provide the neuropathological and behavioral basis for a relevant and reliable PD model.
DOI: 10.1096/fj.03-0677fje
PubMed: 14766796
Affiliations:
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Julie" sort="Blanchet, Julie" uniqKey="Blanchet J" first="Julie" last="Blanchet">Julie Blanchet</name></author><author><name sortKey="Gould, Peter" sort="Gould, Peter" uniqKey="Gould P" first="Peter" last="Gould">Peter Gould</name></author><author><name sortKey="Rouillard, Claude" sort="Rouillard, Claude" uniqKey="Rouillard C" first="Claude" last="Rouillard">Claude Rouillard</name></author><author><name sortKey="Cicchetti, Francesca" sort="Cicchetti, Francesca" uniqKey="Cicchetti F" first="Francesca" last="Cicchetti">Francesca Cicchetti</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2004">2004</date><idno type="RBID">pubmed:14766796</idno><idno type="pmid">14766796</idno><idno type="doi">10.1096/fj.03-0677fje</idno><idno type="wicri:Area/PubMed/Corpus">001356</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001356</idno><idno type="wicri:Area/PubMed/Curation">001356</idno><idno 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xml:lang="en">We investigated the dopaminergic (DA) neuronal degeneration in animals subjected to systemic treatment of rotenone via subcutaneous delivery. Behavioral observations revealed a hypokinetic period in rats sacrificed at 3 and 5 days, and dystonic episodes in animals sacrificed at 8 days. Less than 20% of the total number of animals given rotenone depicted brain lesions after 8 days of treatment, as demonstrated by a significant loss of DA fibers in the striatum, but not of DA nigral neurons. Tyrosine hydroxylase-negative striatal territories were characterized by post-synaptic toxicity as demonstrated by a decreased number of interneurons labeled for choline acetyltransferase, NADPH-diaphorase, parvalbumin, and projection neurons labeled for calbindin and nerve growth factor inducible-B (NGFI-B). Post-synaptic neurodegeneration was demonstrated further by abundant striatal staining for Fluoro-Jade. Decrease in the nuclear orphan receptor Nurr1 expression was the only significant change observed at the level of the substantia nigra. Autopsy reports confirmed that animals suffered from severe digestion problems. These data suggest that hypokinesia observed between 3 and 5 days is the result of general health problems rather than a specific motor deficit associated to Parkinson's disease (PD) symptoms. Overall, the effects of rotenone toxicity are widespread, and subcutaneous administration of this toxin does not provide the neuropathological and behavioral basis for a relevant and reliable PD model.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Blanchet, Julie" sort="Blanchet, Julie" uniqKey="Blanchet J" first="Julie" last="Blanchet">Julie Blanchet</name><name sortKey="Cicchetti, Francesca" sort="Cicchetti, Francesca" uniqKey="Cicchetti F" first="Francesca" last="Cicchetti">Francesca Cicchetti</name><name sortKey="Gould, Peter" sort="Gould, Peter" uniqKey="Gould P" first="Peter" last="Gould">Peter Gould</name><name sortKey="Martinoli, Maria Grazia" sort="Martinoli, Maria Grazia" uniqKey="Martinoli M" first="Maria-Grazia" last="Martinoli">Maria-Grazia Martinoli</name><name sortKey="Rouillard, Claude" sort="Rouillard, Claude" uniqKey="Rouillard C" first="Claude" last="Rouillard">Claude Rouillard</name><name sortKey="St Hilaire, Michel" sort="St Hilaire, Michel" uniqKey="St Hilaire M" first="Michel" last="St-Hilaire">Michel St-Hilaire</name></noCountry><country name="Canada"><noRegion><name sortKey="Lapointe, Nicolas" sort="Lapointe, Nicolas" uniqKey="Lapointe N" first="Nicolas" last="Lapointe">Nicolas Lapointe</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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