The effects of Memantine and MK801 on NMDA receptor switching 2B and 2A subunits in hippocampal cell culture.
DOI:
https://doi.org/10.31157/an.v28i2.410Keywords:
Schizophrenia, synapses, SNARE, glutamate, development, NMDA receptor.Abstract
Background: Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder which onset begins in adolescence or early adulthood. Notwithstanding, the brain dysfunction occurs before the disease and involves the NMDA receptor switch from GluN2B to GluN2A at early neonatal period. We have recently postulated memantine (MEM) as an effective experimental treatment, which may have its root on the modulation of NMDA receptor subunit turnover during the postnatal period by preventing glutamatergic hypofunction in the maternal deprivation model of SCZ. Methods: To explore this possibility, here we have evaluated the turn-over of pre and postsynaptic glutamatergic synaptic components by using primary mouse hippocampal neurons during the synaptic formation period. Results: MK801 stimulation prevented the GluN2B to GluN2A molecular switch at 11 days in vitro (DIV). Importantly, vesicular glutamate transporter 2 (VGLUT2) was also reduced at this time point. MEM treatment reverted these effects by normalizing GluN2B, GluN2A and overexpressing VGLUT2 expression. Conclusion: Our data supports a mechanism by which behavioral abnormalities previously observed in animals after maternal deprivation may be prevented by MEM treatment by regulation of the glutamatergic synaptic molecular composition.
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September 2022-present © Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Open access articles under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. No commercial re-use is allowed.
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January 2014-December 2021 © Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Open access articles under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
