Hippocampal Transcriptome Analysis in a Mouse Model of Chronic Unpredictable Stress Insomnia

<b>Background</b>: This study aimed to develop a model for understanding stress-induced sleep disturbances and to explore the potential interactions between sleep disturbances and mood disturbances. <b>Methods</b>: The chronic unpredictable mild stress (CUMS) group was established using the CUMS method, while the CUMS+Noise group was subjected to an additional 8-h exposure to noise in conjunction with the CUMS protocol. Each group was tested for anxiety and depressive-like behavior using the open-field, elevated plus maze, tail suspension, and forced swimming tests in male C57BL/6J mice. Subsequently, we assessed sleep status using sleep recordings and a standardized scoring system alongside the pentobarbital sodium-induced sleep test. <b>Results</b>: The mice in both model groups exhibited anxiety-like behavior. Sleep disturbances observed in the CUMS+Noise group were characterized by disruptions in sleep duration and circadian rhythm. This observation was supported by a marked reduction in multiple sleep time intervals and single sleep duration, as well as a significant increase in sleep duration at the final time interval of ZT23-24. To further investigate the potential mechanisms of interaction, we conducted an analysis of hub genes present in the hippocampal sequencing data utilizing weighted gene co-expression network analysis (WGCNA). Pearson correlation analysis revealed a significant association between the hub genes <i>Alb</i>, <i>P2rx1</i>, and <i>Npsr1</i> and key phenotypic traits. However, PCR experiments indicated that only <i>Alb</i> showed a significant difference, which aligns with the sequencing results. <b>Conclusions</b>: Albumin is a crucial transporter protein for thyroid hormones and plays a vital role in their metabolism. The interaction between sleep disorders and anxiety-like behavior may be closely linked to the dysfunctional transportation of thyroid hormones by albumin.