Hippocampal Synaptic Plasticity-Associated Protein Expression in a Rat Model of Rett Syndrome
Iyer, Archana Mahadevan
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Rett syndrome is a rare X-linked neurodevelopmental disorder. Mutations in the methyl CpG binding protein 2 (MeCP2) gene is the leading cause for most cases of Rett syndrome, generating severe cognitive impairment in females and some males at a very young age (Zhao et al., 2015). Research across the world from MecP2 null mice models of Rett syndrome reveals dysfunction in the hippocampal region of the brain that is associated with significant alterations in behavior, memory and locomotion. Already existing data from electrophysiology and western blot analysis show severe changes in protein expression, synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD). In our study, we assessed the role of specific synaptic proteins in a MeCP2 KO rat model, to compare the data with the existing mouse models and validate the use of rats as an animal model for Rett syndrome research. Immunoblot analysis revealed decreased expression of calcium calmodulin protein kinase II α (CaMKIIα) and NMDA receptor subunit- GluN2A in both dorsal and ventral hippocampus. No significant change was observed in the NMDA receptor subunit- GluN2B. However, the ratio of GluN2B/GluN2A was significantly increased in the dorsal hippocampus. No significant change was observed in the levels of protein kinase A (PKA), PSD95 and actin. Protein level values obtained in the rat model of MeCP2 knockout gene were comparable (with slight variations for GluN2B and PSD95) to the already published mouse models across the globe in different laboratories with similar experimental conditions. These data suggest that changes in protein expression could affect synaptic plasticity and alter the ratio of long-term potentiation/long-term depression, all of which could promote the clinical manifestations observed in Rett syndrome. Further, these findings indicate that the rat model can be used to study synaptic dysfunction in Rett syndrome related conditions.