The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+ transcriptome with glucocorticoids being an important mediator of the LBN-induced molecular changes. LBN altered the NG2+ transcriptome and these transcriptional effects were correlated with glucocorticoids levels. The functional relevance of one LBN-induced candidate gene, Scn7a, could be confirmed by an increase in the density of voltage-gated sodium (Na_v) channel activated currents in hippocampal NG2+ cells. Scn7a remained upregulated until adulthood in LBN animals, which displayed impaired cognitive performance. Considering that Na_v channels are important for NG2+ cell-to-neuron communication, our findings provide novel insights into the disruption of this process in LBN mice.

早期逆境（ELA）对成人心理健康的有害影响的确切机制仍然难以捉摸。迄今为止，大多数研究仅针对神经元群体，而不认为神经元-神经胶质细胞串扰是与压力相关的脑功能完整性的至关重要的要素。在这里，我们以有限的床上用品和套料（LBN）范式的形式研究了ELA对具有神经稳态（NG2 +细胞）的独特特性的神经胶质亚群的影响。首先，我们在母体行为，后代应激反应的激活和LBN操作结果的异质性之间建立了联系。我们进一步表明，LBN靶向海马NG2 +转录组，糖皮质激素是LBN诱导的分子变化的重要介体。LBN改变了NG2 +转录组，这些转录作用与糖皮质激素水平相关。一种LBN诱导的候选基因的功能相关性，Scn7a可以通过海马NG2 +细胞中电压门控钠（Na _v）通道激活电流密度的增加来证实。Scn7a保持上调直至成年LBN动物成年，这显示出认知能力受损。考虑到娜_v通道是NG2 +细胞与神经元沟通很重要，我们的发现提供了新的见解在LBN小鼠这一进程的中断。