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

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Τίτλος: Memory impairments induced by neonatal excitotoxicity are associated with altered expression of NMDA receptor subunits NR2A and NR2B.
Συγγραφείς: Castañeda-Cabral JL; Laboratorio de Biología de la Neurotransmisión, México. Electronic address: jluis.castaneda@academicos.udg.mx., López-Pérez SJ; Laboratorio de Neuroquímica, México., Contreras-Marín S; Laboratorio de Biología de la Neurotransmisión, México., Castro-Torres RD; Laboratorio de Neurobiotecnología, Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias (CUCBA), Universidad de Guadalajara, Zapopan, Mexico., Ureña-Guerrero ME; Laboratorio de Biología de la Neurotransmisión, México. Electronic address: murena@cucba.udg.mx.
Πηγή: Physiology & behavior [Physiol Behav] 2026 Oct 15; Vol. 315, pp. 115456. Date of Electronic Publication: 2026 Jul 28.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Country of Publication: United States NLM ID: 0151504 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-507X (Electronic) Linking ISSN: 00319384 NLM ISO Abbreviation: Physiol Behav Subsets: MEDLINE
Imprint Name(s): Publication: New York NY : Elsevier Science
Original Publication: Oxford, Eng., Long Island City, Pergamon Press.
Ιατρικοί όροι (MeSH): Receptors, N-Methyl-D-Aspartate*/metabolism , Memory Disorders*/chemically induced , Memory Disorders*/metabolism , Sodium Glutamate*/toxicity , Brain*/metabolism , Brain*/drug effects, Maze Learning/drug effects ; Maze Learning/physiology ; Recognition, Psychology/drug effects ; Recognition, Psychology/physiology ; Animals ; Male ; Animals, Newborn ; Rats ; Rats, Wistar ; Disease Models, Animal
Περίληψη: 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.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare no competing financial interests.
Contributed Indexing: Keywords: Excitotoxicity; Memory; Monosodium glutamate; NMDA receptor
Substance Nomenclature: 0 (Receptors, N-Methyl-D-Aspartate)
0 (NR2B NMDA receptor)
0 (NR2A NMDA receptor)
W81N5U6R6U (Sodium Glutamate)
0 (NR1 NMDA receptor)
Entry Date(s): Date Created: 20260728 Date Completed: 20260807 Latest Revision: 20260807
Update Code: 20260808
DOI: 10.1016/j.physbeh.2026.115456
PMID: 42520952
Βάση Δεδομένων: MEDLINE
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  Data: 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&amp;lt; 0.001) and decreased in the STR (p&amp;lt; 0.01). In contrast, NR2B expression was reduced in the CMC (p&amp;lt; 0.05) and increased in the STR (p&amp;lt; 0.01) and Hp (p&amp;lt; 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.&lt;br /&gt; (Copyright &#169; 2026 Elsevier Inc. All rights reserved.)
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  Data: Declaration of competing interest The authors declare no competing financial interests.
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