Memory impairments induced by neonatal excitotoxicity are associated with altered expression of NMDA receptor subunits NR2A and NR2B.

N-methyl-d-aspartate (NMDA) receptors are typically composed of two NR1 subunits and two NR2 (A-D) subunits. These receptors are overactivated during excitotoxicity, which can alter the expression of their subunits. Neonatal treatment with monosodium glutamate (MSG) induces a long-lasting neurodegenerative process triggered by excitotoxicity and involving multiple alterations in neurotransmission systems. This study aimed to determine whether neonatal MSG treatment modifies the protein expression of NR1, NR2A, and NR2B subunits, and whether these changes are associated with memory impairments in adulthood. Male neonatal rats received 4 g/kg MSG subcutaneously on postnatal days (PD) 1, 3, 5, and 7. At PD 60, protein expression of NR1, NR2A, and NR2B was assessed in the cerebral motor cortex (CMC), striatum (STR), hippocampus (Hp), and entorhinal cortex (EC) using Western blot. Memory performance was evaluated between PD 55 and PD 60 using the Barnes maze and novel object recognition tests. NR1 expression did not show significant changes in any brain region analyzed. NR2A expression was significantly increased in the CMC (p< 0.001) and decreased in the STR (p< 0.01). In contrast, NR2B expression was reduced in the CMC (p< 0.05) and increased in the STR (p< 0.01) and Hp (p< 0.05). MSG-treated animals exhibited impairments in short-term spatial and working memory. These findings indicate that neonatal excitotoxicity induced by MSG leads to long-term, region-specific alterations in NMDA receptor subunit composition, which may disrupt glutamatergic signaling and contribute to cognitive deficits in adulthood.