Relationship between circadian rhythm-related genes and extracellular matrix: implications for sleep deprivation

昼夜节律相关基因与细胞外基质的关系:对睡眠剥夺的影响

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作者:Xuejuan Liu, Jia Sun, Zexia Ling, Tong Dong

Background

Sleep deprivation (SD) can lead to the development of various pathological disorders. The extracellular matrix (ECM) compositions and circadian rhythm genes are two pivotal variables of SD. However, their relationships remain undefined during SD.

Conclusion

The current findings suggest a correlation between ECM composition MMP9 and circadian rhythm-related genes PER2 and TIMELESS in mouse hippocampus after SD, providing a novel understanding of the disorders after SD.

Methods

A mouse SD model was established using a modified multiplatform water environment method. The expression of nerve growth factor (NGF) in mouse hippocampus was detected by an immunofluorescence (IF) method. Protein expression was assessed by western blot, and mRNA analysis was performed by quantitative real-time PCR (qRT-PCR). The differentially expressed genes after SD, the genes associated with stromal score, and gene expression correlation were analyzed by bioinformatic analysis.

Results

The mouse model of SD was successfully established, as evidenced by the changed morphology, increased Bax and NGF levels, and downregulated Bcl-2 in mouse hippocampus after SD. The differentially expressed genes after SD were closely associated with the ECM compositions. The ECM composition metalloproteinase 9 (MMP9) was under-expressed in mouse hippocampus after SD. The hippocampal MMP9 expression was correlated with the expression levels of circadian genes PER2, PER3, TIMELESS, FBXL3, and NFIL3. PER2 and TIMELESS were upregulated in mouse hippocampus after SD.

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