Role of microRNAs in cognitive disorders
MiRNAs are small non-coding RNAs that work as post-transcriptional regulators of gene expression. Recent data demonstrated that miRNAs are expressed in the vertebrate nervous system. This expression is modulated by synaptic activity, which is essential for learning and memory formation. The EU-funded NEURO-MIR-NETWORKS (MicroRNA networks in neuronal development and plasticity) project analysed the role of miRNAs in protein synthesis, neuronal development and plasticity using hippocampus synapses as a model. The main goal of the project was the identification of miRNA-mediated pathways involved in synapse development to provide intervention strategies for mental illness. Researchers found that brain-enriched miRNA such as miR-137 are key for controlling synaptic efficacy and plasticity. MiR-137 association with ID and ASD supports the notion that glutamatergic dysfunction may contribute to the pathogenesis of miR-137-linked cognitive impairments. The study further suggested that miR-137 directly regulates excitatory synaptic function through the modulation of the AMPA type of glutamate receptor. The project researchers also examined the role of miRNAs in ASD using animal models. It was found that a valproic acid (VPA) rat model of ASD exhibits an enlargement of the amygdala, similar to that observed in adolescent ASD individuals. Recent research suggests that altered neuronal development and morphology in ASD cases may result from mistakes in the post-transcriptional processes that are tightly regulated by miRNAs. Researchers examined genome-wide transcriptomics expression in the amygdala of VPA rats and detected elevated miR-181c and miR-30d expression levels. The overexpression correlated with dysregulation of cognate targets of these miRNAs that are involved in neuronal system development. Collectively, project results provide a framework for understanding how dysregulation of miRNAs in the brain may contribute to the pathophysiology of ID and ASD. The neuronal disease-based animal models developed within this project may find applications in developing innovative miRNA-based therapies.
