Neuroprotection of midbrain dopamine neurons by nicotine is gated by cytoplasmic Ca2+.
Identifieur interne : 001551 ( Main/Exploration ); précédent : 001550; suivant : 001552Neuroprotection of midbrain dopamine neurons by nicotine is gated by cytoplasmic Ca2+.
Auteurs : Damien Toulorge [France] ; Serge Guerreiro ; Audrey Hild ; Uwe Maskos ; Etienne C. Hirsch ; Patrick P. MichelSource :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2011.
English descriptors
- KwdEn :
- Animals, Calcium (metabolism), Calcium Channels, T-Type (metabolism), Calmodulin (metabolism), Cell Survival (drug effects), Cytoplasm (metabolism), Dopamine (metabolism), Glial Cell Line-Derived Neurotrophic Factor (metabolism), Ion Channel Gating (drug effects), Mesencephalon (cytology), Mesencephalon (drug effects), Mesencephalon (metabolism), Mice, Models, Neurological, Neurons (drug effects), Neurons (metabolism), Neuroprotective Agents (pharmacology), Nicotine (pharmacology), Potassium Channel Blockers (pharmacology), Proto-Oncogene Proteins c-akt (metabolism), Rats, Receptors, Nicotinic (metabolism), Signal Transduction (drug effects), Tetraethylammonium (pharmacology), Tissue Culture Techniques, alpha7 Nicotinic Acetylcholine Receptor.
- MESH :
- chemical , metabolism : Calcium, Calcium Channels, T-Type, Calmodulin, Dopamine, Glial Cell Line-Derived Neurotrophic Factor, Proto-Oncogene Proteins c-akt, Receptors, Nicotinic.
- cytology : Mesencephalon.
- drug effects : Cell Survival, Ion Channel Gating, Mesencephalon, Neurons, Signal Transduction.
- metabolism : Cytoplasm, Mesencephalon, Neurons.
- chemical , pharmacology : Neuroprotective Agents, Nicotine, Potassium Channel Blockers, Tetraethylammonium.
- Animals, Mice, Models, Neurological, Rats, Tissue Culture Techniques, alpha7 Nicotinic Acetylcholine Receptor.
Abstract
Epidemiological and experimental evidence indicates that nicotine is protective for Parkinson disease vulnerable dopamine neurons, but the underlying mechanism of this effect remains only partly characterized. To address this question, we established rat midbrain cultures maintained in experimental conditions that favor the selective and spontaneous loss of dopamine neurons. We report here that nicotine afforded neuroprotection to dopamine neurons (EC(50)=0.32 μM) but only in a situation where cytosolic Ca(2+) (Ca(2+)(cyt)) was slightly and chronically elevated above control levels by concurrent depolarizing treatments. By a pharmacological approach, we demonstrated that the rise in Ca(2+)(cyt) was necessary to sensitize dopamine neurons to the action of nicotine through a mechanism involving α-bungarotoxin-sensitive (presumably α7) nicotinic acetylcholine receptors (nAChRs) and secondarily T-type voltage-gated calcium channels. Confirming the role played by α7 nAChRs in this effect, nicotine had no protective action in midbrain cultures prepared from genetically engineered mice lacking this receptor subtype. Signaling studies revealed that Ca(2+)(cyt) elevations evoked by nicotine and concomitant depolarizing treatments served to activate a survival pathway involving the calcium effector protein calmodulin and phosphatidylinositol 3-kinase. Collectively, our data support the idea that the protective action of nicotine for dopamine neurons is activity-dependent and gated by Ca(2+)(cyt).
DOI: 10.1096/fj.11-182824
PubMed: 21507900
Affiliations:
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Hirsch</name></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21507900</idno><idno type="pmid">21507900</idno><idno type="doi">10.1096/fj.11-182824</idno><idno type="wicri:Area/PubMed/Corpus">000954</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000954</idno><idno type="wicri:Area/PubMed/Curation">000914</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000914</idno><idno type="wicri:Area/PubMed/Checkpoint">000914</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000914</idno><idno type="wicri:Area/Ncbi/Merge">000D08</idno><idno type="wicri:Area/Ncbi/Curation">000D08</idno><idno type="wicri:Area/Ncbi/Checkpoint">000D08</idno><idno type="wicri:Area/Main/Merge">001629</idno><idno type="wicri:Area/Main/Curation">001551</idno><idno type="wicri:Area/Main/Exploration">001551</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Neuroprotection of midbrain dopamine neurons by nicotine is gated by cytoplasmic Ca2+.</title><author><name sortKey="Toulorge, Damien" sort="Toulorge, Damien" uniqKey="Toulorge D" first="Damien" last="Toulorge">Damien Toulorge</name><affiliation wicri:level="3"><nlm:affiliation>Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, Unité Mixte de Recherche-S975, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, Unité Mixte de Recherche-S975, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Guerreiro, Serge" sort="Guerreiro, Serge" uniqKey="Guerreiro S" first="Serge" last="Guerreiro">Serge Guerreiro</name></author><author><name sortKey="Hild, Audrey" sort="Hild, Audrey" uniqKey="Hild A" first="Audrey" last="Hild">Audrey Hild</name></author><author><name sortKey="Maskos, Uwe" sort="Maskos, Uwe" uniqKey="Maskos U" first="Uwe" last="Maskos">Uwe Maskos</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name></author></analytic><series><title level="j">FASEB journal : official publication of the Federation of American Societies for Experimental Biology</title><idno type="eISSN">1530-6860</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Calcium (metabolism)</term><term>Calcium Channels, T-Type (metabolism)</term><term>Calmodulin (metabolism)</term><term>Cell Survival (drug effects)</term><term>Cytoplasm (metabolism)</term><term>Dopamine (metabolism)</term><term>Glial Cell Line-Derived Neurotrophic Factor (metabolism)</term><term>Ion Channel Gating (drug effects)</term><term>Mesencephalon (cytology)</term><term>Mesencephalon (drug effects)</term><term>Mesencephalon (metabolism)</term><term>Mice</term><term>Models, Neurological</term><term>Neurons (drug effects)</term><term>Neurons (metabolism)</term><term>Neuroprotective Agents (pharmacology)</term><term>Nicotine (pharmacology)</term><term>Potassium Channel Blockers (pharmacology)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>Rats</term><term>Receptors, Nicotinic (metabolism)</term><term>Signal Transduction (drug effects)</term><term>Tetraethylammonium (pharmacology)</term><term>Tissue Culture Techniques</term><term>alpha7 Nicotinic Acetylcholine Receptor</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term><term>Calcium Channels, T-Type</term><term>Calmodulin</term><term>Dopamine</term><term>Glial Cell Line-Derived Neurotrophic Factor</term><term>Proto-Oncogene Proteins c-akt</term><term>Receptors, Nicotinic</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Mesencephalon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term><term>Ion Channel Gating</term><term>Mesencephalon</term><term>Neurons</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cytoplasm</term><term>Mesencephalon</term><term>Neurons</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Neuroprotective Agents</term><term>Nicotine</term><term>Potassium Channel Blockers</term><term>Tetraethylammonium</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Mice</term><term>Models, Neurological</term><term>Rats</term><term>Tissue Culture Techniques</term><term>alpha7 Nicotinic Acetylcholine Receptor</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Epidemiological and experimental evidence indicates that nicotine is protective for Parkinson disease vulnerable dopamine neurons, but the underlying mechanism of this effect remains only partly characterized. To address this question, we established rat midbrain cultures maintained in experimental conditions that favor the selective and spontaneous loss of dopamine neurons. We report here that nicotine afforded neuroprotection to dopamine neurons (EC(50)=0.32 μM) but only in a situation where cytosolic Ca(2+) (Ca(2+)(cyt)) was slightly and chronically elevated above control levels by concurrent depolarizing treatments. By a pharmacological approach, we demonstrated that the rise in Ca(2+)(cyt) was necessary to sensitize dopamine neurons to the action of nicotine through a mechanism involving α-bungarotoxin-sensitive (presumably α7) nicotinic acetylcholine receptors (nAChRs) and secondarily T-type voltage-gated calcium channels. Confirming the role played by α7 nAChRs in this effect, nicotine had no protective action in midbrain cultures prepared from genetically engineered mice lacking this receptor subtype. Signaling studies revealed that Ca(2+)(cyt) elevations evoked by nicotine and concomitant depolarizing treatments served to activate a survival pathway involving the calcium effector protein calmodulin and phosphatidylinositol 3-kinase. Collectively, our data support the idea that the protective action of nicotine for dopamine neurons is activity-dependent and gated by Ca(2+)(cyt).</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Guerreiro, Serge" sort="Guerreiro, Serge" uniqKey="Guerreiro S" first="Serge" last="Guerreiro">Serge Guerreiro</name><name sortKey="Hild, Audrey" sort="Hild, Audrey" uniqKey="Hild A" first="Audrey" last="Hild">Audrey Hild</name><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name><name sortKey="Maskos, Uwe" sort="Maskos, Uwe" uniqKey="Maskos U" first="Uwe" last="Maskos">Uwe Maskos</name><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Toulorge, Damien" sort="Toulorge, Damien" uniqKey="Toulorge D" first="Damien" last="Toulorge">Damien Toulorge</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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