MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

Abstract

Despite dopamine-glutamate aberrant interaction that has long been considered a relevant landmark of psychosis pathophysiology, several aspects of these two neurotransmitters reciprocal interaction remain to be defined. The emerging role of postsynaptic density (PSD) proteins at glutamate synapse as a molecular "lego" making a functional hub where different signals converge may add a new piece of information to understand how dopamine-glutamate interaction may work with regard to schizophrenia pathophysiology and treatment. More recently, compelling evidence suggests a relevant role for microRNA (miRNA) as a new class of dopamine and glutamate modulators with regulatory functions in the reciprocal interaction of these two neurotransmitters. Here, we aimed at addressing the following issues: (i) Do miRNAs have a role in schizophrenia pathophysiology in the context of dopamine-glutamate aberrant interaction? (ii) If miRNAs are relevant for dopamine-glutamate interaction, at what level this modulation takes place? (iii) Finally, will this knowledge open the door to innovative diagnostic and therapeutic tools? The biogenesis of miRNAs and their role in synaptic plasticity with relevance to schizophrenia will be considered in the context of dopamine-glutamate interaction, with special focus on miRNA interaction with PSD elements. From this framework, implications both for biomarkers identification and potential innovative interventions will be considered.

Disruptions of sensorimotor gating, cytokines, glycemia, monoamines, and genes in both sexes of rats reared in social isolation can be ameliorated by oral chronic quetiapine administration

“…Levels of DA and 5-HT are reduced in the hippocampus, was similar to the findings of Brenes and Fornaguera (2009). In fact, multiple cross talks among dopamine and other central neurotransmitters (including glutamate and serotonin) may serve to interpret the pathogenesis of schizophrenia (Guillin et al, 2007;de Bartolomeis et al, 2014). IR-induced stress affects cortico-striatal ATP and DA, mediating pro-CK release and resulting in PPI deficits (Möller et al, 2013a), and it attenuates the 5-HT level in the brain, leading to increased demand for 5-HT (Brenes and Fornaguera, 2009).…”

Genetic and Morphological Features of Human iPSC-Derived Neurons with Chromosome 15q11.2 (BP1-BP2) Deletions

“…The iPSC-neurons from the control and the deletion bearing individuals were relatively premature. Our preliminary observations, which need to be confirmed using unbiased quantitative analyses, are an important step towards understanding the changes in dendritic spine number, shape and plasticity that have been reported in the pathogenesis of intellectual disability, Fragile X syndrome, ASD and SZ (19, 35, 36). Earlier rodent studies indicate that CYFIP1 overexpression or haploinsufficiency increase immature spine number, suggesting an important role for CYFIP1 in dendritic spine morphology (17).…”

Common developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS)

“…miRNAs influence gene expression at the transcription level, by promoting mRNA degradation and by inhibiting mRNA translation (Bartel, 2009; Younger and Corey, 2011). Earlier studies have shown that some miRNAs may be dysregulated in the brains of schizophrenia patients (de Bartolomeis et al, 2015; Hill et al, 2014). We performed small-RNA seq (Terranova et al, 2015) to identify and to measure the miRNA levels in NCC lines from the three controls (C1, C2, C4) and three schizophrenic patients (P1, P2, P3).…”