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Instituto Nacional de Neurología y Neurocirugía

2023, Number 2

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Arch Neurocien 2023; 28 (2)

The effects of memantine and mk 801 on nmda receptor switching 2b and 2a subunits in hippocampal cell culture

Uribe E, Sanchez-Mendoza E

Language: English
References: 34
Page: 20-27
PDF size: 286.83 Kb.


ABSTRACT

Background: Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder whose onset begins in adolescence or early adulthood. Notwithstanding, brain dysfunction occurs before the disease onset and involves a switch in NMDA receptor subunit composition from GluN2B to GluN2A at early neonatal period. We have recently postulated memantine (MEM) as an effective experimental treatment, due to its effect on modulating NMDA receptor subunit turnover during the postnatal period, as it prevents glutamatergic hypofunction in the maternal deprivation model of SCZ. Methods: We evaluated the turnover 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). Vesicular glutamate transporter 2 (VGLUT2) was also reduced at this time point. MEM treatment reverted these effects by normalizing GluN2B, and GluN2A, and over-expressing VGLUT2 expression. Conclusion: Our data supports a molecular mechanism by which SCZ may be prevented with MEM treatment through regulation of the glutamatergic synaptic molecular composition.


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