We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior. Pharmacologically, modulating histone acetylation with acetyl-L-carnitine (LAC) or acetyl-N-cysteine (NAC) rapidly increases xCT and activates a network with mGlu2 receptors to prime an enhanced glutamate homeostasis that promotes both pro-resilient and antidepressant-like responses. Pharmacological xCT blockage counteracts NAC prophylactic effects. GFAP+-Cre-dependent overexpression of xCT in vDG mimics pharmacological actions in promoting resilience. This work establishes a mechanism by which vDG protection leads to stress resilience and antidepressant responses via epigenetic programming of an xCT-mGlu2 network.
Pubmed ID: 29024663 RIS Download
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This polyclonal secondary targets IgY (H+L)
View all literature mentionsThis monoclonal targets Metabotropic Glutamate Receptor 2
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis polyclonal targets CREB1
View all literature mentionsThis polyclonal targets Green Fluorescent Protein (GFP)
View all literature mentionsThis polyclonal targets CREB
View all literature mentionsThis polyclonal targets GFAP - Astrocyte Marker
View all literature mentionsMus musculus with name B6.Cg-Tg(Gfap-cre)73.12Mvs/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6NCrl from IMSR.
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View all literature mentionsSoftware Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsDatabase for mapping gene expression profiles to pathways and genomes. Repository of microarray gene expression profile data for Synechocystis PCC6803 (syn), Bacillus subtilis (bsu), Escherichia coli W3110 (ecj), Anabaena PCC7120 (ana), and other species contributed by the Japanese research community.
View all literature mentionsMus musculus with name C57BL/6NCrl from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Gfap-cre)73.12Mvs/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Gfap-cre)73.12Mvs/J from IMSR.
View all literature mentionsThis polyclonal secondary targets IgY (H+L)
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