Toxicity of Annonaceae for dopaminergic neurons: Potential role in atypical parkinsonism in Guadeloupe
Identifieur interne : 000465 ( France/Analysis ); précédent : 000464; suivant : 000466Toxicity of Annonaceae for dopaminergic neurons: Potential role in atypical parkinsonism in Guadeloupe
Auteurs : Annie Lannuzel [France] ; Patrick P. Michel [France] ; Dominique Caparros-Lefebvre [France] ; Jacqueline Abaul ; Reynald Hocquemiller ; Merle Ruberg [France]Source :
- Movement Disorders [ 0885-3185 ] ; 2002-01.
Descripteurs français
- Pascal (Inist)
- Wicri :
- geographic : Guadeloupe.
- topic : Homme.
English descriptors
- KwdEn :
- Annonaceae, Annonaceae (adverse effects), Antiparkinson Agents (antagonists & inhibitors), Antiparkinson Agents (therapeutic use), Apoptosis (drug effects), Atypical, Cell Culture Techniques, Cell culture, Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins, Dopaminergic neuron, Drug Resistance, Etiology, Gabaergic neuron, Guadeloupe, Guadeloupe (epidemiology), Human, Humans, Immunohistochemistry, Levodopa (antagonists & inhibitors), Levodopa (therapeutic use), Membrane Glycoproteins, Membrane Transport Proteins (drug effects), Mesencephalon (drug effects), Mesencephalon (pathology), Nerve Tissue Proteins, Neurons (drug effects), Neurons (metabolism), Parkinsonian Disorders (drug therapy), Parkinsonian Disorders (epidemiology), Parkinsonism, Toxicity, apoptosis, movement disorders, neurotoxicology, parkinsonism.
- MESH :
- chemical , antagonists & inhibitors : Antiparkinson Agents, Levodopa.
- chemical , drug effects : Membrane Transport Proteins.
- geographic , epidemiology : Guadeloupe.
- adverse effects : Annonaceae.
- drug effects : Apoptosis, Mesencephalon, Neurons.
- drug therapy : Parkinsonian Disorders.
- epidemiology : Parkinsonian Disorders.
- chemical , metabolism : Dopamine, Neurons.
- pathology : Mesencephalon.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- Cell Culture Techniques, Dopamine Plasma Membrane Transport Proteins, Drug Resistance, Humans, Membrane Glycoproteins, Nerve Tissue Proteins.
Abstract
In the French West Indies there is an abnormally high frequency of levodopa‐resistant parkinsonism, suggested to be caused by consumption of fruit and infusions of tropical plants, especially Annona muricata (corossol, soursop). To determine whether toxic substances from this plant can cause the neuronal degeneration or dysfunction underlying the syndrome, we exposed mesencephalic dopaminergic neurons in culture to the total extract (totum) of alkaloids from Annona muricata root bark and to two of the most abundant subfractions, coreximine and reticuline. After 24 hours, 50% of dopaminergic neurons degenerated with 18 μg/ml totum, 4.3 μg/ml (13 μM) coreximine, or 100 μg/ml (304 μM) reticuline. The effects of the alkaloid totum were not restricted to the population of dopaminergic cells since GABAergic neurons were also affected by the treatment. Nuclei in dying neurons showed DNA condensation or fragmentation, suggesting that neuronal death occurred by apoptosis. Cell death was not excitotoxic and did not require toxin uptake by the dopamine transporter. Neurodegeneration was attenuated by increasing the concentration of glucose in the culture medium, which also reduced the effect of the dopaminergic neurotoxin MPP+, a mitochondrial respiratory chain inhibitor. Toxin withdrawal after short‐term exposure arrested cell death. Acute treatment with totum, coreximine, or reticuline reversibly inhibited dopamine uptake by a mechanism that was distinct from that causing neuronal death. GABA uptake was not reduced under the same conditions. This study suggests that alkaloids from A. muricata can modulate the function and the survival of dopaminergic nerve cells in vitro. It is therefore conceivable that repeated consumption could cause the neuronal dysfunction and degeneration underlying the West Indian parkinsonian syndrome. © 2002 Movement Disorder Society.
Url:
DOI: 10.1002/mds.1246
Affiliations:
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ISTEX:AD39733D539A8E3F82FD91ECED1722F0F74B48A5Le document en format XML
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Michel</name></author><author><name sortKey="Caparros Efebvre, Dominique" sort="Caparros Efebvre, Dominique" uniqKey="Caparros Efebvre D" first="Dominique" last="Caparros-Lefebvre">Dominique Caparros-Lefebvre</name></author><author><name sortKey="Abaul, Jacqueline" sort="Abaul, Jacqueline" uniqKey="Abaul J" first="Jacqueline" last="Abaul">Jacqueline Abaul</name></author><author><name sortKey="Hocquemiller, Reynald" sort="Hocquemiller, Reynald" uniqKey="Hocquemiller R" first="Reynald" last="Hocquemiller">Reynald Hocquemiller</name></author><author><name sortKey="Ruberg, Merle" sort="Ruberg, Merle" uniqKey="Ruberg M" first="Merle" last="Ruberg">Merle Ruberg</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:AD39733D539A8E3F82FD91ECED1722F0F74B48A5</idno><date when="2002" year="2002">2002</date><idno type="doi">10.1002/mds.1246</idno><idno type="url">https://api.istex.fr/document/AD39733D539A8E3F82FD91ECED1722F0F74B48A5/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000B32</idno><idno type="wicri:Area/Istex/Curation">000B32</idno><idno type="wicri:Area/Istex/Checkpoint">002B45</idno><idno type="wicri:doubleKey">0885-3185:2002:Lannuzel A:toxicity:of:annonaceae</idno><idno type="wicri:Area/Main/Merge">006259</idno><idno type="wicri:source">INIST</idno><idno type="RBID">Pascal:02-0207159</idno><idno type="wicri:Area/PascalFrancis/Corpus">002815</idno><idno type="wicri:Area/PascalFrancis/Curation">000506</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">002577</idno><idno type="wicri:doubleKey">0885-3185:2002:Lannuzel A:toxicity:of:annonaceae</idno><idno type="wicri:Area/Main/Merge">006616</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:11835443</idno><idno type="wicri:Area/PubMed/Corpus">003B95</idno><idno type="wicri:Area/PubMed/Curation">003B95</idno><idno type="wicri:Area/PubMed/Checkpoint">003899</idno><idno type="wicri:Area/Ncbi/Merge">000656</idno><idno type="wicri:Area/Ncbi/Curation">000656</idno><idno type="wicri:Area/Ncbi/Checkpoint">000656</idno><idno type="wicri:doubleKey">0885-3185:2002:Lannuzel A:toxicity:of:annonaceae</idno><idno type="wicri:Area/Main/Merge">006110</idno><idno type="wicri:Area/Main/Curation">004254</idno><idno type="wicri:Area/Main/Exploration">004254</idno><idno type="wicri:Area/France/Extraction">000465</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Toxicity of Annonaceae for dopaminergic neurons: Potential role in atypical parkinsonism in Guadeloupe</title><author><name sortKey="Lannuzel, Annie" sort="Lannuzel, Annie" uniqKey="Lannuzel A" first="Annie" last="Lannuzel">Annie Lannuzel</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Service de Neurologie, Centre hospitalier universitaire des Antilles et de la Guyane, Pointe‐à‐Pitre, Guadeloupe</wicri:regionArea><wicri:noRegion>Guadeloupe</wicri:noRegion><wicri:noRegion>Guadeloupe</wicri:noRegion></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. 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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2002-01">2002-01</date><biblScope unit="vol">17</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="84">84</biblScope><biblScope unit="page" to="90">90</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">AD39733D539A8E3F82FD91ECED1722F0F74B48A5</idno><idno type="DOI">10.1002/mds.1246</idno><idno type="ArticleID">MDS1246</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Annonaceae</term><term>Annonaceae (adverse effects)</term><term>Antiparkinson Agents (antagonists & inhibitors)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Apoptosis (drug effects)</term><term>Atypical</term><term>Cell Culture Techniques</term><term>Cell culture</term><term>Dopamine (metabolism)</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Dopaminergic neuron</term><term>Drug Resistance</term><term>Etiology</term><term>Gabaergic neuron</term><term>Guadeloupe</term><term>Guadeloupe (epidemiology)</term><term>Human</term><term>Humans</term><term>Immunohistochemistry</term><term>Levodopa (antagonists & inhibitors)</term><term>Levodopa (therapeutic use)</term><term>Membrane Glycoproteins</term><term>Membrane Transport Proteins (drug effects)</term><term>Mesencephalon (drug effects)</term><term>Mesencephalon (pathology)</term><term>Nerve Tissue Proteins</term><term>Neurons (drug effects)</term><term>Neurons (metabolism)</term><term>Parkinsonian Disorders (drug therapy)</term><term>Parkinsonian Disorders (epidemiology)</term><term>Parkinsonism</term><term>Toxicity</term><term>apoptosis</term><term>movement disorders</term><term>neurotoxicology</term><term>parkinsonism</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Membrane Transport Proteins</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>Guadeloupe</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Annonaceae</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Mesencephalon</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Mesencephalon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Culture Techniques</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Drug Resistance</term><term>Humans</term><term>Membrane Glycoproteins</term><term>Nerve Tissue Proteins</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Annona muricata</term><term>Annonaceae</term><term>Atypique</term><term>Culture cellulaire</term><term>Etiologie</term><term>Guadeloupe</term><term>Homme</term><term>Immunohistochimie</term><term>Neurone dopaminergique</term><term>Neurone gabaergique</term><term>Parkinsonisme</term><term>Toxicité</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Guadeloupe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In the French West Indies there is an abnormally high frequency of levodopa‐resistant parkinsonism, suggested to be caused by consumption of fruit and infusions of tropical plants, especially Annona muricata (corossol, soursop). To determine whether toxic substances from this plant can cause the neuronal degeneration or dysfunction underlying the syndrome, we exposed mesencephalic dopaminergic neurons in culture to the total extract (totum) of alkaloids from Annona muricata root bark and to two of the most abundant subfractions, coreximine and reticuline. After 24 hours, 50% of dopaminergic neurons degenerated with 18 μg/ml totum, 4.3 μg/ml (13 μM) coreximine, or 100 μg/ml (304 μM) reticuline. The effects of the alkaloid totum were not restricted to the population of dopaminergic cells since GABAergic neurons were also affected by the treatment. Nuclei in dying neurons showed DNA condensation or fragmentation, suggesting that neuronal death occurred by apoptosis. Cell death was not excitotoxic and did not require toxin uptake by the dopamine transporter. Neurodegeneration was attenuated by increasing the concentration of glucose in the culture medium, which also reduced the effect of the dopaminergic neurotoxin MPP+, a mitochondrial respiratory chain inhibitor. Toxin withdrawal after short‐term exposure arrested cell death. Acute treatment with totum, coreximine, or reticuline reversibly inhibited dopamine uptake by a mechanism that was distinct from that causing neuronal death. GABA uptake was not reduced under the same conditions. This study suggests that alkaloids from A. muricata can modulate the function and the survival of dopaminergic nerve cells in vitro. It is therefore conceivable that repeated consumption could cause the neuronal dysfunction and degeneration underlying the West Indian parkinsonian syndrome. © 2002 Movement Disorder Society.</div></front></TEI><affiliations><list><country><li>France</li></country><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Abaul, Jacqueline" sort="Abaul, Jacqueline" uniqKey="Abaul J" first="Jacqueline" last="Abaul">Jacqueline Abaul</name><name sortKey="Hocquemiller, Reynald" sort="Hocquemiller, Reynald" uniqKey="Hocquemiller R" first="Reynald" last="Hocquemiller">Reynald Hocquemiller</name></noCountry><country name="France"><noRegion><name sortKey="Lannuzel, Annie" sort="Lannuzel, Annie" uniqKey="Lannuzel A" first="Annie" last="Lannuzel">Annie Lannuzel</name></noRegion><name sortKey="Caparros Efebvre, Dominique" sort="Caparros Efebvre, Dominique" uniqKey="Caparros Efebvre D" first="Dominique" last="Caparros-Lefebvre">Dominique Caparros-Lefebvre</name><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><name sortKey="Ruberg, Merle" sort="Ruberg, Merle" uniqKey="Ruberg M" first="Merle" last="Ruberg">Merle Ruberg</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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