m(6)A Modification Involves in Enriched Environment-Induced Neurogenesis and Cognition Enhancement

Although previous studies have shown that an enriched environment (EE) promotes neurogenesis and alters DNA and histone modifications, it remains largely unknown whether an EE affects epitranscriptome in the context of neuronal development. Here, we showed that EE exposure enhanced the pool of adult neural stem/progenitor cells (aNSPCs) and promoted neuronal differentiation of aNSPCs. EE exposure also improved cognitive capabilities and altered the expression of genes relating to neuronal development, neurogenesis, and memory. N-6-Methyladenosine (m(6)A) immunoprecipitation combined with deep sequencing (MeRIP-seq) data analysis revealed that EE exposure increased the global level of m(6)A and led to differential m(6)A mRNA modification. Differential m(6)A modification-associated genes are involved in neuronal development, neurogenesis, and so on. Notably, EE exposure decreased the protein level of m(6)A eraser Fto, but did not affect the protein level of m(6)A writers METTL3 and METTL14. Taken together, our results suggest that enriched environment exposure induces differential m(6)A mRNA modification and adds a novel layer to the interaction between the environment and epigenetics in the context of postnatal neuronal development.