Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system
Identifieur interne : 001B84 ( Main/Exploration ); précédent : 001B83; suivant : 001B85Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system
Auteurs : Ken Nakamura [États-Unis] ; Lisa Won [États-Unis] ; Alfred Heller [États-Unis] ; Un Jung Kang [États-Unis]Source :
- Brain Research [ 0006-8993 ] ; 2000.
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Abstract
Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson’s disease (PD), and could initiate dopaminergic neuronal degeneration. Nevertheless, we have previously demonstrated that mesencephalic dopaminergic neurons in primary monolayer cultures are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. To extend this finding to a system that more closely resembles the in vivo situation, we characterized the effects of glutathione depletion on reaggregate cultures derived from ventral mesencephalic and their striatal target neurons, as well as supporting elements including glia. Dopaminergic neurons were found to be more resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, than other nigrostriatal neurons, while striatal target cells exhibited an intermediate susceptibility when examined after 48 h. Glutathione depletion, however, decreased the intracellular content of catecholamines after 48 h and eventually led to the loss of dopaminergic neurons after 7 days. Our data indicate that the intrinsic resistance of dopaminergic neurons to the toxicity of glutathione depletion occurs in a variety of experimental paradigms, and suggest that global glutathione depletion alone is unlikely to account for the selective loss of dopaminergic neurons in PD. Rather, it is more likely that either the selective loss of glutathione from dopaminergic neurons, or the combination of glutathione loss with other insults contributes to the preferential death of dopaminergic neurons in PD.
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DOI: 10.1016/S0006-8993(00)02425-2
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Nevertheless, we have previously demonstrated that mesencephalic dopaminergic neurons in primary monolayer cultures are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. To extend this finding to a system that more closely resembles the in vivo situation, we characterized the effects of glutathione depletion on reaggregate cultures derived from ventral mesencephalic and their striatal target neurons, as well as supporting elements including glia. Dopaminergic neurons were found to be more resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, than other nigrostriatal neurons, while striatal target cells exhibited an intermediate susceptibility when examined after 48 h. Glutathione depletion, however, decreased the intracellular content of catecholamines after 48 h and eventually led to the loss of dopaminergic neurons after 7 days. Our data indicate that the intrinsic resistance of dopaminergic neurons to the toxicity of glutathione depletion occurs in a variety of experimental paradigms, and suggest that global glutathione depletion alone is unlikely to account for the selective loss of dopaminergic neurons in PD. Rather, it is more likely that either the selective loss of glutathione from dopaminergic neurons, or the combination of glutathione loss with other insults contributes to the preferential death of dopaminergic neurons in PD.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Nakamura, Ken" sort="Nakamura, Ken" uniqKey="Nakamura K" first="Ken" last="Nakamura">Ken Nakamura</name></region><name sortKey="Heller, Alfred" sort="Heller, Alfred" uniqKey="Heller A" first="Alfred" last="Heller">Alfred Heller</name><name sortKey="Kang, Un Jung" sort="Kang, Un Jung" uniqKey="Kang U" first="Un Jung" last="Kang">Un Jung Kang</name><name sortKey="Kang, Un Jung" sort="Kang, Un Jung" uniqKey="Kang U" first="Un Jung" last="Kang">Un Jung Kang</name><name sortKey="Won, Lisa" sort="Won, Lisa" uniqKey="Won L" first="Lisa" last="Won">Lisa Won</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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