These studies suggest that miRNAs can not only be used to diagnose, but can also be used for treatment response. Conclusion and future directions Based on studies showing the involvement of miRNAs in neural plasticity, neurogenesis, and stress response, it is clear that miRNAs may participate in the pathogenesis of MDD. More direct evidence comes from human postmortem brain studies showing aberrant expression of miRNAs in the prefrontal cortical area. From these, as well as animal studies showing a blunted response Inhibitors,research,lifescience,medical in NLII rats, one can assume that miRNAs may actively

participate in developing the MDD phenotype. Despite these findings, one needs to find an integrated view of miRNA networks and the pathways that are affected by these miRNAs. It is well established that a combination of miRNAs is a much more powerful regulator than individual miRNAs. Interestingly, differential c-expression of a group of miRNAs has not only been shown to play a direct role in human disease pathogenesis, but they also help Inhibitors,research,lifescience,medical in identifying the nature of disordered pathways implicated in such pathogenesis.34-37 A set of miRNAs that are significantly affected in MDD, and the corresponding set of mRNAs that are affected in the same samples, will help resolve this issue. The affected miRNAs and mRNAs are likely to interact with and regulate each other, either directly

as targets or indirectly Inhibitors,research,lifescience,medical as part of larger regulatory networks. One can also identify sets of miRNAs that are not correlated in expression across individuals in the control group, yet are positively correlated in the MDD group and vice versa. There is a possibility that the correlated miRNAs and mRNAs are likely to be

driven in their expression by the same (possibly overlapping) set Inhibitors,research,lifescience,medical of transcription factors or epigenetic influences. If a given miRNA is driven by one transcription factor in the control group and by a different transcription factor in the MDD group, this may result in no change in its mean expression levels across groups, yet may be detectable by observing shifts in the miRNAs that are tuclazepam Inhibitors,research,lifescience,medical correlated across individuals. In addition, it is important to determine whether the changes in miRNA/mRNA network are similar or different across different brain areas and more so, whether they are cell type-specific and are reversible. Also important is to examine the potential reasons for altered miRNA expression. Is it because of genetic changes in the promoter region FG-4592 upstream of primary miRNA gene transcripts, the pre-miRNA hairpin, or the mature miRNA, or due to RNA editing of transcripts or epigenetic suppression of the chromosomal region encoding the miRNAs? A variety of enzymes are responsible for processing miRNAs. These include Drosha, Dicer and cofactors DGCR8, TRBR and PACT. Several of these proteins have been shown to be modified post-translationally in a dynamic manner.