Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat.

Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat.
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DOI:
10.1016/j.etap.2011.12.027
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发表时间:
2012-03
影响因子:
4.3
通讯作者:
Henderson GI
Henderson GI
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Rathinam ML;Watts LT;Narasimhan M;Riar AK;Mahimainathan L;Henderson GI

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Primary cultures of fetal rat cortical neurons and astrocytes were used to test the hypothesis that astrocyte-mediated control of neuronal glutathione (GSH) is a potent factor in neuroprotection against rotenone and paraquat. In neurons, rotenone (0.025 to 1μM) for 4 and 24 h decreased viability as did paraquat (2 to 100μM). Rotenone (30nM) decreased neuronal viability and GSH by 24% and 30%, while ROS were increased by 56%. Paraquat (30μM) decreased neuronal viability and GSH by 36% and 70%, while ROS were increased by 23%. When neurons were co-cultured with astrocytes, their GSH increased 1.5 fold and 5 fold at 12 and 24 h. Co-culturing with astrocytes blocked neuronal death and damage by rotenone and paraquat. Astrocyte-mediated neuroprotection was dependent on the activity of components of the γ-glutamyl cycle. These studies illustrate the importance of astrocyte-mediated glutathione homeostasis for protection of neurons from rotenone and paraquat and the role of the γ-glutamyl cycle in this neuroprotection
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