MicroRNAs as effectors of brain function

In the relatively short time since their discovery, the miRNAs have been shown to be essential for neuronal development, survival, function, and plasticity. MiRNAs are regulated in response to ischemia and ischemic preconditioning, and male and female mice show both common and unique responses to ischemia, which may contribute to sexually dimorphic responses to ischemia. These findings warrant further studies to examine the role of ischemia-regulated miRNAs on cell death and/or neuroprotection and to identify new targets for alternative strategies for the treatment or prevention of stroke. Given that miRNAs are encoded within the genome, it is conceivable that mutations in miRNA genes and/or their mRNA target sequences, could disrupt normal post-transcriptional gene regulation and lead to disease phenotypes. This may be particularly true for familial diseases, such as stroke, where protein coding gene mutations have not been identified. MiRNAs are also rapidly emerging as biomarkers for diseases, including brain injury, neurodegeneration, and psychiatric disorders.22 Accordingly, there is evidence for altered miRNA expression in peripheral blood isolated from ischemic stroke patients,23,24 suggesting the possibility that blood miRNAs can be used as biomarkers for brain injury, including cerebral ischemia. The first decade of miRNA research has greatly impacted our understanding of the mechanisms underlying normal and altered cellular function, despite technical limitations due to the complexity of miRNAs. In the next decade of miRNA studies, efforts to advance and evolve the tools necessary for analysis and validation of miRNAs, should be fully supported, as these tools will be essential in establishing direct correlations between miRNA-mediated posttranscriptional gene expression and disease, a matter of great importance to human health.