Zocher Sara, Schilling Susan, Grzyb Anna N, Adusumilli Vijay S, Bogado Lopes Jadna, Günther Sandra, Overall Rupert W, Winter York, Kempermann Gerd
German Center for Neurodegenerative Diseases (DZNE) Dresden, Tatzberg 41, 01307 Dresden, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany.
Sci Adv. 2020 Aug 26;6(35):eabb1478. doi: 10.1126/sciadv.abb1478. eCollection 2020 Aug.
Individuals differ in their response to environmental stimuli, but the stability of individualized behaviors and their associated changes in brain plasticity are poorly understood. We developed a novel model of enriched environment to longitudinally monitor 40 inbred mice exploring 35 connected cages over periods of 3 to 6 months. We show that behavioral individuality that emerged during the first 3 months of environmental enrichment persisted when mice were withdrawn from the enriched environment for 3 additional months. Behavioral trajectories were associated with stable interindividual differences in adult hippocampal neurogenesis and persistent epigenetic effects on neuronal plasticity genes in the hippocampus. Using genome-wide DNA methylation sequencing, we show that one-third of the DNA methylation changes were maintained after withdrawal from the enriched environment. Our results suggest that, even under conditions that control genetic background and shared environment, early-life experiences result in lasting individualized changes in behavior, brain plasticity, and epigenetics.
个体对环境刺激的反应存在差异，但对于个体行为的稳定性及其相关的大脑可塑性变化，我们却知之甚少。我们开发了一种新颖的丰富环境模型，用于纵向监测40只近交系小鼠在3至6个月的时间里探索35个相连笼子的情况。我们发现，在环境丰富化的前3个月出现的行为个性，在小鼠从丰富环境中撤出并额外饲养3个月后依然存在。行为轨迹与成年海马神经发生中稳定的个体间差异以及海马体中神经元可塑性基因上持续的表观遗传效应相关。通过全基因组DNA甲基化测序，我们发现，从丰富环境撤出后，三分之一的DNA甲基化变化得以维持。我们的研究结果表明，即使在控制了遗传背景和共享环境的条件下，早期生活经历也会导致行为、大脑可塑性和表观遗传学方面持久的个性化变化。
