The miRNA-mediated gene regulatory network in hippocampus and hypothalamus of the aging mouse

Aging leads to time-dependent functional decline of all major organs. In particular, the aging brain is susceptible to cognitive decline and several neurodegenerative diseases. To characterize the aging process and understand the underlying molecular mechanisms, numerous studies have examined changes in gene expression in the aging mouse brain using high-throughput sequencing. However, microRNA-mediated post-transcriptional regulation of gene expression has not yet been comprehensively elucidated. In this study, we performed global analysis of mRNA and microRNA expression simultaneously in the hypothalamus and hippocampus of young and aged mice. We identified aging-dependent differentially expressed genes, most of which were specific to the hypothalamus or hippocampus. For mRNA sequencing, a total of 6 samples were prepared from each hippocampus and hypothalamus tissue, 3 biological replicates in young (2 months old) and aged mice (15 months old). For small-RNA sequencing, a total of 6 samples were prepared from each hippocampus and hypothalamus tissue, 3 biological replicates in young (2 months old) and aged mice (15 months old).衰老会导致所有主要器官出现随时间推移的功能衰退。尤为关键的是，衰老的大脑易发生认知衰退，并罹患多种神经退行性疾病。为解析衰老进程并阐明其潜在分子机制，已有众多研究借助高通量测序技术，对衰老小鼠大脑中的基因表达变化展开了分析。然而，微RNA（microRNA）介导的基因表达转录后调控机制，至今尚未得到全面阐释。本研究同时对年轻与衰老小鼠的下丘脑和海马体组织中的信使RNA（mRNA）与微RNA表达水平开展了全局分析，鉴定出了衰老依赖性差异表达基因，其中绝大多数仅在下丘脑或海马体中特异性表达。在mRNA测序环节，研究团队从海马体与下丘脑组织中各制备了6份样本，其中年轻小鼠（2月龄）与衰老小鼠（15月龄）各设3个生物学重复。在小RNA测序环节，研究团队同样从海马体与下丘脑组织中各制备了6份样本，其中年轻小鼠（2月龄）与衰老小鼠（15月龄）各设3个生物学重复。