Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory.

Autor:	Acutain MF; Instituto de Biología Celular y Neurociencia 'Prof. E. De Robertis' (IBCN, CONICET-UBA), Buenos Aires, Argentina., Griebler Luft J; Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Vazquez CA; Instituto de Biología Celular y Neurociencia 'Prof. E. De Robertis' (IBCN, CONICET-UBA), Buenos Aires, Argentina., Popik B; Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Cercato MC; Instituto de Biología Celular y Neurociencia 'Prof. E. De Robertis' (IBCN, CONICET-UBA), Buenos Aires, Argentina., Epstein A; CGMC, University Lyon I, Lyon, France., Salvetti A; International Center for Infectiology Research (CIRI), INSERM U1111, CNRS UMR5308, Université de Lyon (UCBL1), Lyon, France., Jerusalinsky DA; Instituto de Biología Celular y Neurociencia 'Prof. E. De Robertis' (IBCN, CONICET-UBA), Buenos Aires, Argentina., de Oliveira Alvares L; Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Baez MV; Instituto de Biología Celular y Neurociencia 'Prof. E. De Robertis' (IBCN, CONICET-UBA), Buenos Aires, Argentina.; 1° U.A. Departamento de Histologia, Embriología, Biologia Celular y Genética, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2021 Apr 09; Vol. 15, pp. 644100. Date of Electronic Publication: 2021 Apr 09 (Print Publication: 2021).
DOI:	10.3389/fnins.2021.644100
Abstrakt:	N -methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, both in vitro in primary cultured hippocampal neurons and in vivo in adult male Wistar rats. After in vitro characterization, we performed a cognitive profile and evaluated seizure susceptibility in vivo . Our in vitro results showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNA in vivo displayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning-memory mechanisms. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Acutain, Griebler Luft, Vazquez, Popik, Cercato, Epstein, Salvetti, Jerusalinsky, de Oliveira Alvares and Baez.)
Databáze:	MEDLINE
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