Evaluation of the protective effect of oestradiol against toxicity induced by 6-hydroxydopamine and 1-methyl-4-phenylpyridinium ion (MPP+) towards dopaminergic mesencephalic neurones in primary culture
Identifieur interne : 000285 ( France/Analysis ); précédent : 000284; suivant : 000286Evaluation of the protective effect of oestradiol against toxicity induced by 6-hydroxydopamine and 1-methyl-4-phenylpyridinium ion (MPP+) towards dopaminergic mesencephalic neurones in primary culture
Auteurs : Sophie Callier [France, Canada] ; Maryvonne Le Saux [France] ; Anne-Marie Lhiaubet [France] ; Thérèse Di Paolo [Canada] ; William Rostene [France] ; Didier Pelaprat [France]Source :
- Journal of neurochemistry [ 0022-3042 ] ; 2002.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Recent findings suggest that gonadal steroid hormones are neuroprotective and may provide clinical benefits in delaying the development of Parkinson's disease. In this report we investigated the ability of oestradiol to protect mesencephalic dopaminergic neurones cultured in serum-free or serum-supplemented medium from toxicity induced by 6-hydroxy-dopamine or 1-methyl-4-phenylpyridinium ion (MPP+). The efficiency of both toxins and oestradiol was evaluated by tyrosine hydroxylase (TH) immunocytochemistry, [3H]dopamine ([3H]DA) uptake, length of dopaminergic processes and lactate dehydrogenase (LDH) release measurement. In cultures grown in serum-supplemented medium, a 2-h pre-treatment with high concentrations (10-100 μM) of 17β-oestradiol or 17α-oestradiol, the stereoisomer with weak oestrogenic activity, protected both dopaminergic and non-dopaminergic neurones from toxicity induced by 6-hydroxydopamine (6-OHDA; 40 or 100 μM) and by the high MPP+ concentrations (50 μM) necessary to obtain significant neuronal death under those culture conditions. At these concentrations, MPP+ was no longer selective for dopaminergic neurones but affected all cells present in the culture. In contrast, the hormonal treatments did not protect against selective degeneration of dopaminergic neurones induced by lower MPP+ concentrations (below 10 μM), related to inhibition of complex I of respiratory chain. In cultures grown in serum-free medium, oestradiol concentrations higher than 1 μM induced neuronal degeneration and no protection against 6-OHDA or MPP+ toxicity was observed at lower concentrations of the steroid. The neuroprotective effects of 17a- or 17p-oestradiol evidenced in this model might be due to the antioxidant properties of these compounds. However, other non-genomic effects of the steroids cannot be excluded.
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Hopital saint Antoine</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><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="Pelaprat, Didier" sort="Pelaprat, Didier" uniqKey="Pelaprat D" first="Didier" last="Pelaprat">Didier Pelaprat</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Unité 339 INSERM. Hopital saint Antoine</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>17α-Estradiol</term><term>17β-Estradiol</term><term>Animal</term><term>Antioxidant</term><term>Cell death</term><term>Dopaminergic neuron</term><term>In vitro</term><term>Midbrain</term><term>Neuroprotective agent</term><term>Neurotoxin</term><term>Parkinson disease</term><term>Rat</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Mésencéphale</term><term>Neurone dopaminergique</term><term>Neurotoxine</term><term>Mort cellulaire</term><term>Neuroprotecteur</term><term>17α-Oestradiol</term><term>17β-Oestradiol</term><term>Antioxydant</term><term>In vitro</term><term>Animal</term><term>Parkinson maladie</term><term>Rat</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recent findings suggest that gonadal steroid hormones are neuroprotective and may provide clinical benefits in delaying the development of Parkinson's disease. In this report we investigated the ability of oestradiol to protect mesencephalic dopaminergic neurones cultured in serum-free or serum-supplemented medium from toxicity induced by 6-hydroxy-dopamine or 1-methyl-4-phenylpyridinium ion (MPP<sup>+</sup>). The efficiency of both toxins and oestradiol was evaluated by tyrosine hydroxylase (TH) immunocytochemistry, [<sup>3</sup>H]dopamine ([<sup>3</sup>H]DA) uptake, length of dopaminergic processes and lactate dehydrogenase (LDH) release measurement. In cultures grown in serum-supplemented medium, a 2-h pre-treatment with high concentrations (10-100 μM) of 17β-oestradiol or 17α-oestradiol, the stereoisomer with weak oestrogenic activity, protected both dopaminergic and non-dopaminergic neurones from toxicity induced by 6-hydroxydopamine (6-OHDA; 40 or 100 μM) and by the high MPP<sup>+</sup> concentrations (50 μM) necessary to obtain significant neuronal death under those culture conditions. At these concentrations, MPP<sup>+</sup> was no longer selective for dopaminergic neurones but affected all cells present in the culture. In contrast, the hormonal treatments did not protect against selective degeneration of dopaminergic neurones induced by lower MPP<sup>+</sup> concentrations (below 10 μM), related to inhibition of complex I of respiratory chain. In cultures grown in serum-free medium, oestradiol concentrations higher than 1 μM induced neuronal degeneration and no protection against 6-OHDA or MPP<sup>+</sup> toxicity was observed at lower concentrations of the steroid. The neuroprotective effects of 17a- or 17p-oestradiol evidenced in this model might be due to the antioxidant properties of these compounds. However, other non-genomic effects of the steroids cannot be excluded.</div></front></TEI><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Callier, Sophie" sort="Callier, Sophie" uniqKey="Callier S" first="Sophie" last="Callier">Sophie Callier</name></region><name sortKey="Le Saux, Maryvonne" sort="Le Saux, Maryvonne" uniqKey="Le Saux M" first="Maryvonne" last="Le Saux">Maryvonne Le Saux</name><name sortKey="Lhiaubet, Anne Marie" sort="Lhiaubet, Anne Marie" uniqKey="Lhiaubet A" first="Anne-Marie" last="Lhiaubet">Anne-Marie Lhiaubet</name><name sortKey="Pelaprat, Didier" sort="Pelaprat, Didier" uniqKey="Pelaprat D" first="Didier" last="Pelaprat">Didier Pelaprat</name><name sortKey="Rostene, William" sort="Rostene, William" uniqKey="Rostene W" first="William" last="Rostene">William Rostene</name></country><country name="Canada"><noRegion><name sortKey="Callier, Sophie" sort="Callier, Sophie" uniqKey="Callier S" first="Sophie" last="Callier">Sophie Callier</name></noRegion><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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