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

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 remain poorly understood. A notable candidate molecular mechanism is that of microRNA, a family of 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 in some brain disorders and associated preclinical models. Recent studies exploring the effects of stimulating environments on microRNA levels in the brain have revealed an array of changes that are likely to have important downstream effects on gene expression, and thus may regulate a variety of cellular processes. Here we review literature that explores the differential expression of microRNAs in rodents following environmental enrichment and exercise, in both healthy control animals and preclinical models of relevance to neurological and psychiatric disorders. •Stimulating environments and physical exercise promote brain health.•Experience-dependent changes to microRNA expression occur following environmental modifications.•microRNA composition is altered after environmental enrichment and exercise in healthy controls.•Changes to microRNA expression may underlie the benefit of environmental interventions in brain disorders.•microRNA-directed therapies are an exciting prospect in the future of precision medicine.