Luke T Geiger, Julie-Anne Balouek, Lorna A Farrelly, Andy S Chen, Megan Tang, Shannon N Bennett, Eric J Nestler, Benjamin A Garcia, Ian Maze, Catherine Jensen Peña
Early-life stress increases sensitivity to subsequent stress, which has been observed among humans, other animals, at the level of cellular activity, and at the level of gene expression. However, the molecular mechanisms underlying such long-lasting sensitivity are poorly understood. We tested the hypothesis that persistent changes in transcription and transcriptional potential were maintained at the level of the epigenome, through changes in chromatin. We used a combination of bottom-up mass spectrometry, viral-mediated epigenome-editing, behavioral quantification, and RNA-sequencing in a mouse model of early-life stress, focusing on the ventral tegmental area (VTA), a brain region critically implicated in motivation, reward learning, stress response, and mood and drug disorders...
March 14, 2024: bioRxiv