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To address this question, we co\u2010culture astrocytes with genetically labeled neurons, permitting their separation by flow cytometry, and test whether the presence of neurons influences the astrocyte transcriptome. We find that numerous pathways are regulated in the co\u2010cultured astrocytes, in a time\u2010dependent matter coincident with synaptic maturation. In particular, the induction of glutathione metabolic genes is prominent, resulting in increased glutathione production. We show that the induction of the glutathione pathway is mediated by astrocytic metabotropic glutamate receptors. Using a candidate approach, we identify direct binding of the nuclear factor E2\u2010related factor, NRF2, to several of the induced genes. Blocking nuclear accumulation of astrocytic NRF2 abolishes neuron\u2010induced glutathione gene induction and glutathione production. 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