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  • Title: Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat.
    Author: Rathinam ML, Watts LT, Narasimhan M, Riar AK, Mahimainathan L, Henderson GI.
    Journal: Environ Toxicol Pharmacol; 2012 Mar; 33(2):353-60. PubMed ID: 22301167.
    Abstract:
    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 (0.025-1 μM) for 4 and 24 h decreased viability as did paraquat (2-100 μM). Rotenone (30 nM) decreased neuronal viability and GSH by 24% and 30%, while ROS were increased by 56%. Paraquat (30 μM) 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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