Gas5 regulates early life stress-induced anxiety and spatial memory

Abstract

The early life stress (ES) of maternal separation (MS) evokes anxiety and memory deficits. Emerging studies have shown that MS-induced gene expression in the hippocampus is operated at the level of transcription. However, the involvement of non-coding RNAs in MS-induced behavioural deficits is poorly understood. Here, we have explored the role of synapse-enriched long non-coding RNAs (lncRNAs) in anxiety and memory upon MS. We observed that MS led to an enhancement of expression of the lncRNA Gas5 (Growth Arrest Specific-5) in the hippocampus; accompanied by increased levels of anxiety and deficits in spatial memory. The knockdown of Gas5 in early life could reduce anxiety and partially rescue the spatial memory deficit of maternally separated adult mice following MS. Gene Ontology analysis revealed that Gas5 exerts its function by regulating RNA metabolism and translation. Our study highlights the importance of MS-regulated lncRNA in anxiety and spatial memory.SIGNIFICANCE STATEMENTThe mechanism of early-life stress-induced gene expression and its implications in associated behavioural deficits are poorly resolved. The study fills this void by identifying lncRNA as a regulatory factor linked with early life stress of maternal separation. This study demonstrates that the reversal of Gas5 expression, a synapse-enriched lncRNA, enables the partial rescue of anxiety and memory deficits. Our study highlights an RNA-based approach to alleviate the adverse effects of early life stress.