How the enriched get richer? Experience-dependent modulation of microRNAs and the therapeutic effects of environmental enrichment.

Abstract Environmental enrichment and physical exercise have many well-established health benefits. Although these environmental manipulations are known to delay symptom onset and progression in a variety of neurological and psychiatric conditions, the mechanisms underlying these effects remains poorly understood. A notable candidate molecular mechanism involves microRNAs, which are small noncoding RNAs that are important regulators of gene expression. Research investigating the many diverse roles of microRNAs has greatly expanded over the past decade, with several promising preclinical and clinical studies highlighting the role of dysregulated microRNA expression (in the brain, blood and other peripheral systems) in understanding the aetiology of disease. Altered microRNA levels have also been described following environmental interventions such as exercise and environmental enrichment in non-clinical populations and wild-type animals, as well as some brain disorders and preclinical models. Recent studies exploring the effects of environmental interventions on miRNA levels in the brain have revealed a variety of changes that are likely to have important downstream effects on gene expression, and thus regulate a variety of cellular processes. Here, we review the literature on differential expression of miRNAs in rodents following environmental enrichment and exercise, in both healthy control animals and preclinical models of neurological and psychiatric disorders.