Transcriptomic Analysis of lncRNAs and their mRNA Networks in Cerebral Ischemia in Young and Aged Mice

Ischemic stroke comprises 75% of all strokes and it is associated with a great frailty and casualty rate. Certain data suggest multiple long non-coding Ribonucleic Acids (lncRNAs) assist the transcriptional, post-transcriptional, and epigenetic regulation of genes expressed in the CNS (Central Nervous System). However, these studies generally focus on differences in the expression patterns of lncRNAs and Messenger Ribonucleic Acids (mRNAs) in tissue samples before and after cerebral ischemic injury, ignoring the effects of age.

In this study, differentially expressed lncRNA analysis was performed based on RNAseq data from the transcriptomic analysis of murine brain microglia related to cerebral ischemia injury in mice at different ages (10 weeks and 18 months).

The results showed that the number of downregulate differentially expressed genes (DEGs) in aged mice was 37 less than in young mice. Among them, lncRNA Gm-15987, RP24- 80F7.5, XLOC_379730, XLOC_379726 were significantly down-regulated. Then, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these specific lncRNAs were mainly related to inflammation. Based on the lncRNA/mRNA coexpression network, the mRNA co-expressed with lncRNA was mainly enriched in pathways, such as immune system progression, immune response, cell adhesion, B cell activation, and T cell differentiation. Our results indicate that the downregulation of lncRNA, such as Gm-15987, RP24- 80F7.5, XLOC_379730, and XLOC_379726 in aged mice may attenuate microglial-induced inflammation via the progress of immune system progression immune response, cell adhesion, B cell activation, and T cell differentiation.

The reported lncRNAs and their target mRNA during this pathology have potentially key regulatory functions in the cerebral ischemia in aged mice while being important for diagnosing and treating cerebral ischemia in the elderly.