Identify the key genes and pathways of melatonin in age-dependent mice hippocampus regulation by transcriptome analysis

Context: Dysregulation of energy metabolism is a fundamental contributor to all the hallmarks of brain aging. Melatonin, primarily secreted by the pineal gland, is closely associated with molecules and signaling pathways that sense and affect energy metabolism. However, the impact of melatonin on age-related mRNA expression in the hippocampus of mice at different ages remains poorly understood. Objective: The present study conducted transcriptome analysis of the hippocampus in melatonin-exposed mice at 9, 13, and 25 months of age. Differential gene analysis, GO and KEGG pathway enrichment analysis, GSEA analysis, as well as weighted gene co-expression network analysis (WGCNA), were performed on the transcriptome data. Results: Our study demonstrated that melatonin exerts a more pronounced regulatory effect on the transcriptome of 25-month old mice, and significantly enhances the expression level of TTR in the hippocampus of 13-month old mice. WGCNA analysis revealed that melatonin primarily modulates the energy metabolism of mouse hippocampus through the mTOR signaling pathway and AMPK signaling pathway. Conclusions: In conclusion, our study provides new insights into the comprehensive understanding of the mechanism of melatonin's age-dependent regulation of the mice hippocampus.