Interestingly, they found that the synaptic enrichment was not simply related to the specificity of miRNA expression within neurons, but they arise from precursors that are expressed in the synaptic fractions and associated tightly

with postsynaptic density (PSD).65 Furthermore, the synaptic enrichment of miRNAs was related to structural features of their precursors, suggesting a basis by which pre- Inhibitors,research,lifescience,medical or pri-miRNA may be selectively and stably transported to dendrites.124 Since both Dicer and pre-RNAs are expressed in synaptic fractions and are strongly associated with PSD, it suggests that at least a portion of the mature miRNAs are locally processed near synapses. Dicer is released from PSD and its RNase III activity is markedly

enhanced following stimuli such Inhibitors,research,lifescience,medical as N-methyl-D-aspartate (NMDA) that can cause an increase in local calcium and activation of calpain. Dicer is expressed in PSDs, but is enzymatically inactive until conditions that activate calpain cause its liberation.65,68 These findings suggest that miRNAs are Inhibitors,research,lifescience,medical formed, at least in part, by the processing of miRNA precursors locally within dendritic spines, and synaptic stimulation may lead to local processing of miRNA precursors in proximity to the synapse. Synaptic efficacy can be regulated by modulating miRNA functions at the synapse and consequently synaptic plasticity due to the critical feature of miRNAs to regulate gene circuitry locally at the synapse in an activity-dependent fashion. This may Selleck Selumetinib provide Inhibitors,research,lifescience,medical a unique opportunity at the therapeutic level, where regulation of miRNA can be used to control plasticity at the synapse. miRNAs in MDD pathogenesis and treatment The diagnostic and prognostic values of miRNA have been established in various types of cancer.125 Inhibitors,research,lifescience,medical The

potential of miRNAs as diagnostic markers for psychiatric and neurodegenerative diseases has been advancing rapidly.31,126-128 Phosphoprotein phosphatase Both preclinical and clinical evidence demonstrates that miRNAs can be extensively involved in stress-related disorders and MDD, as well as the antidepressant response. Coping response to stress and miRNAs An individual’s ability to cope with stress is critical in the development of MDD. We recently examined miRNA expression in both the frontal cortex of rats who developed behavior (learned helpless [LH]) that resembles stress-induced depression and those who did not develop depression (nonlearned helpless [NLH]), even though they received similar inescapable shocks (Table I).