| First Author | Peña CJ | Year | 2017 |
| Journal | Science | Volume | 356 |
| Issue | 6343 | Pages | 1185-1188 |
| PubMed ID | 28619944 | Mgi Jnum | J:243966 |
| Mgi Id | MGI:5912745 | Doi | 10.1126/science.aan4491 |
| Citation | Pena CJ, et al. (2017) Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science 356(6343):1185-1188 |
| abstractText | Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. This work establishes a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2. |
