Social isolation is a growing public health concern across the lifespan. Specifically, isolation early in life, during critical periods of brain development, increases the risk of psychiatric disorders later in life. Previous studies of isolation models in mice have shown distinct neurological abnormalities in various regions of the brain, but the mechanism linking the experience of isolation to these phenotypes is unclear. In this study, we show that ΔFosB, a long-lived transcription factor associated with neuronal activity, chronic stress, and drug-induced neuroplasticity, is upregulated in the prelimbic/infralimbic (PL/IL) region of the cortex and hippocampus of adult C57BL/6J mice transiently isolated for two weeks post-weaning. Additionally, a related transcription factor, FosB, is also increased in the PL/IL in socially isolated females.In contrast, both ΔFosB and FosB are increased in male mice isolated for six weeks from weaning until tissue collection. These results show that short-term isolation during the critical post-weaning period has long-lasting and sex-dependent effects on gene expression in brain and that FosB/ΔFosB expression provides a potential mechanistic link between post-weaning social isolation and associated neurological abnormalities.

社会隔离是整个生命周期中日益关注的公共卫生问题。具体而言，在生命的早期，大脑发育的关键时期进行隔离会增加在生命后期出现精神疾病的风险。先前对小鼠隔离模型的研究表明，大脑各个区域都有明显的神经异常，但是将隔离经验与这些表型联系起来的机制尚不清楚。在这项研究中，我们显示ΔFosB是与神经元活动，慢性应激和药物诱导的神经可塑性相关的长寿命转录因子，在成年C57BL的皮质和海马区的前缘/下缘（PL / IL）区上调/ 6J小鼠在断奶后暂时隔离了两周。另外，在社会隔离的女性中，相关的转录因子FosB在PL / IL中也增加。相反，从断奶到收集组织六周的雄性小鼠，ΔFosB和FosB均增加。这些结果表明，在断奶后的关键时期进行短期隔离对大脑中的基因表达具有长期且性别依赖性的作用，并且FosB /ΔFosB的表达为断奶后的社会隔离与相关的神经系统异常之间提供了潜在的机制联系。 。