Cognitive impairment induced by psychological stress is time-of-day of exposure dependent in female rats

Circadian rhythms have evolved in almost all organisms to adapt day-night cycle and control a broad range of bodily functions including appetite, activity and response to environmental disturbances. Here, for the first time, we performed terrified-sound stress model in female rats during different time of a day (in daytime or nighttime) for 21 days to explore the effects of circadian rhythms on psychological stress (PS)-induced cognitive impairment outcome. Our results showed that PS in daytime (PS-D) led to a worse impaired short-term memory but not spatial learning memory. As for PS during nighttime (PS-N), a more severe impairment in spatial learning performance was discovered accompanying with a less impaired short-term memory performance. Further GO enrichment and KEGG analysis of DEGs found items including axon guidance, negative regulation of neuron apoptotic process, memory and synapse organization and cell projection, and pathways including axon guidance, GABAergic synapse, calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway and circadian entrainment, indicating that the mechanisms were related to neurons and synapse. Golgi staining discovered that a decreased number of interactions and dendritic spines only in PS-N, which was consistent with the lower expression of PSD95 in hippocampus. What's more, BDNF was significantly decreased in both stressed groups, while SYN had no change. All these results demonstrated that circadian rhythms have a great influence on cognitive performance and hippocampal neuron after being stressed, and it seems that PS in nighttime will come with more severe cognitive impairment.