Astrocyte Mediated Protection of Fetal Cerebral Cortical Neurons from Rotenone and Paraquat

Overview

Journal Environ Toxicol Pharmacol

Date 2012 Feb 4

PMID 22301167

Citations 18

Authors

Mary Latha Rathinam

Lora Talley Watts

Madhusudhanan Narasimhan

Amanjot Kaur Riar

Lenin Mahimainathan

George I Henderson

Affiliations

Soon will be listed here.

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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