Reduced expression of GluN2A induces a delay in neuron maturation

Decreased expression of GluN2A causes an imbalance in the GluN2A/GluN2B ratio that delays neuron maturation and induces a more immature phenotype, characterized by the presence of immature dendritic spines and increased branching. This delay in maturation leads in turn to enhanced responses to glutamate stimulus, which may cause sensitization for seizure outcome. AbstractNMDA receptors (NMDARs) play an important role in synaptic plasticity both in physiological and pathological conditions. GluN2A and GluN2B are the most expressed NMDAR regulatory subunits, in the hippocampus and other cognitive-related brain structures. GluN2B is characteristic of immature structures and GluN2A of mature ones. Changes in GluN2A expression were associated with complex phenotypes that led to complex neurodevelopmental disorders, including the occurrence of seizures. However, little is known about the role of GluN2A in these phenotypes. In this work, we reduced GluN2A expression in mature neuronal cultures and observed an altered GluN2A/GluN2B ratio. Furthermore, those neurons exhibit an increase in immature dendritic spines and dendritic branching, as well as an increased response to glutamate stimulus. This phenotype (considering GluN2A/GluN2B ratio, index branching and glutamate response) resembles those observed at immature neuronal stages in  vitro. We propose that this immature phenotype led to a higher response to glutamate stimulus which, in vivo, would be the basis of reduced threshol...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research