Transcriptome analysis using RNA sequencing of the hippocampus of aged LPAR2-/- versus wildtype control mice

We assessed the effect of a deletion of the lysophosphatidic acid receptor, LPAR2 in mice on gene regulation in the hippocampus of aged mice by comparing RNA-seq expression profiles. Presynaptic LPAR2 fortifies the release of glutamate, hence increases neuronal excitability and baseline activity. LPAR2 deficiency prevents an age-associated hyperexcitability and decline of hippocampal long-term-potentiation and improves repose and attention in behaving animals. RNAseq was performed to assess if these protective features manifested at the expressional level of pro-longevity or pro-aging genes. A total number of 18126 genes was reliably detected, and 16420 passed the filtering criteria of >3 valid samples per group. GSEA gene set enrichment analysis was used for gene ranking and identication of top up- and downregulated genes and evaluation of their functions based on P-value, Q-value, fold change and abundance. Among the top downregulated genes were several typical neuronal activity markers including Fos, Fosb, Egr2 suggesting that indeed neuronal baseline activity was lower in LPAR2-/- hippocampus. Hippocampal RNA from middle aged to aged mice was analyzed by RNA sequencing of 7 biological replicates using an Illumina HiSeq4000 system.