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

Background

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.

Methods

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.

Results

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 Alb, P2rx1, and Npsr1 and key phenotypic traits. However, PCR experiments indicated that only Alb showed a significant difference, which aligns with the sequencing results.

Conclusions

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.