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

Mary Latha Rathinam, Lora Talley Watts, Madhusudhanan Narasimhan, Amanjot Kaur Riar, Lenin Mahimainathan, George I. Henderson

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalEnvironmental Toxicology and Pharmacology
Volume33
Issue number2
DOIs
StatePublished - Mar 1 2012

Keywords

  • γ-Glutamyl cycle
  • Astrocytes
  • Glutathione
  • Neurons
  • Paraquat
  • Rotenone

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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