Transcriptional profiling of mouse prefrontal cortex and nucleus accumbens under chronic jet lag

Chronic jet lag (CJL) induced by shifting light-dark cycles repeatedly is a commonly used protocol to mimic the environmental light/dark changes encountered by shift workers. We conducted RNA sequencing using prefrontal cortex (PFC) and nucleus accumbens (NAc) tissues from these animals, which are brains regions strongly implicated in the pathology of various neurological and psychiatric conditions. Our results reveal the alterations of brain activities and systematic reprogramming of gene expression in brain tissues under CJL, building hypothesis for how CJL increases the susceptibility to neurological and psychiatric diseases. 8-week-old male C57BL/6J mice purchased from Model Animal Research Center of Nanjing University were assigned to different cages randomly with approximately 5 animals per cage. Animals were housed in light-tight cabinets with time-controlled illumination. Food and sterilized water were accessible ad libitum. The mice were housed under 12 hour light: 12 hour dark (12L12D) for 2 weeks for entrainment prior to CJL treatment. For CJL group, lights on and off times were advanced by 6 hours every 2 days whereas for control group they remain unchanged. On CJL Day 10, PFC and NAc were harvested from 3 control and 3 CJL treated animals at Zeitgeber Time 1 (ZT1, 1 hour after lights on; ZT0 is defined as the time of lights on) and ZT13, respectively.通过反复切换明暗周期诱导的慢性时差（chronic jet lag, CJL）是模拟倒班工作者所经历的环境明暗节律变化的常用实验范式。我们对该类动物的前额叶皮层（prefrontal cortex, PFC）与伏隔核（nucleus accumbens, NAc）组织进行了RNA测序，这两个脑区与多种神经及精神疾病的病理过程密切相关。本研究结果揭示了慢性时差环境下脑活动的改变以及脑组织内基因表达的系统性重编程，为解析慢性时差如何提升神经及精神疾病易感性提供了假说基础。实验采用购自南京大学模型动物研究中心的8周龄雄性C57BL/6J小鼠，将其随机分组饲养于笼盒中，每笼约5只。所有小鼠均饲养于具备时间可控光照的避光柜内，可自由采食饲料与灭菌饮用水。在进行慢性时差处理前，小鼠先在12小时光照:12小时黑暗（12L12D）的光周期条件下饲养2周以完成节律同步化。慢性时差组的光照启闭时间每2天提前6小时，而对照组的光照周期则保持恒定不变。在慢性时差处理第10天，分别于授时因子时间1（ZT1，光照开启后1小时；ZT0定义为光照开启时刻）与ZT13时刻，从3只对照组小鼠与3只慢性时差处理组小鼠体内采集前额叶皮层与伏隔核组织。