| First Author | Nasca C | Year | 2017 |
| Journal | Neuron | Volume | 96 |
| Issue | 2 | Pages | 402-413.e5 |
| PubMed ID | 29024663 | Mgi Jnum | J:256101 |
| Mgi Id | MGI:6114361 | Doi | 10.1016/j.neuron.2017.09.020 |
| Citation | Nasca C, et al. (2017) Role of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in Resilience to Stress. Neuron 96(2):402-413.e5 |
| abstractText | 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. |
