United States Department of Health & Human Services National Institutes of Health (NIH) - USA [R21MH098793]

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United States Department of Health & Human Services National Institutes of Health (NIH) - USA [R21MH098793]

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Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression

Francija, Ester; Petrović, Zorica; Brkić, Željka; Mitić, Miloš; Radulović, Jelena; Adžić, Miroslav

(2019)

TY  - JOUR
AU  - Francija, Ester
AU  - Petrović, Zorica
AU  - Brkić, Željka
AU  - Mitić, Miloš
AU  - Radulović, Jelena
AU  - Adžić, Miroslav
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8450
AB  - Recent reports have demonstrated that lipopolysaccharide (LPS)-induced depressive-like behaviour is mediated via NMDA receptor. In this study, we further investigated the role of GluN2 A subunit of NMDA receptor in synaptic processes in the prefrontal cortex (PFC) and hippocampus of GluN2 A knockout (KO) mice in LPS-induced depressive-like behavior. Our data suggest that LPS-treated mice, lacking GluN2 A subunit, did not exhibit depressive-like behaviour. This was accompanied by unaltered levels of IL-6 and significant changes in neuroplasticity markers and glutamate receptor subunits composition in PFC and hippocampus. In particular, an immune challenge in GluN2 A KO mice resulted in unchanged PSA-NCAM levels and proBDNF increase in both brain structures as well as in increase in BDNF levels in hippocampus. Furthermore, the absence of GluN2 A resulted in increased levels of all NCAM isoforms in PFC upon LPS which was followed with a decrease in GluN1 and GluN2B subunits. The levels of AMPA receptor subunits (GluA1, GluA3, and GluA4) in the hippocampus of GluN2 A mice were unaltered upon the treatment and abundantly present in the PFC of KO mice. These results indicate that the GluN2 A subunit is critical in neuroinflammation-related depression, that its absence abolishes LPS-induced depressive phenotype, sustains PSA-NCAM levels, increases proBDNF signalling in the PFC and hippocampus and potentiates synaptic stabilization through NCAM in the PFC upon an immune challenge. © 2018 Elsevier B.V.
T2  - Behavioural Brain Research
T1  - Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression
VL  - 359
SP  - 550
EP  - 559
DO  - 10.1016/j.bbr.2018.10.011
ER  - 
@article{
author = "Francija, Ester and Petrović, Zorica and Brkić, Željka and Mitić, Miloš and Radulović, Jelena and Adžić, Miroslav",
year = "2019",
abstract = "Recent reports have demonstrated that lipopolysaccharide (LPS)-induced depressive-like behaviour is mediated via NMDA receptor. In this study, we further investigated the role of GluN2 A subunit of NMDA receptor in synaptic processes in the prefrontal cortex (PFC) and hippocampus of GluN2 A knockout (KO) mice in LPS-induced depressive-like behavior. Our data suggest that LPS-treated mice, lacking GluN2 A subunit, did not exhibit depressive-like behaviour. This was accompanied by unaltered levels of IL-6 and significant changes in neuroplasticity markers and glutamate receptor subunits composition in PFC and hippocampus. In particular, an immune challenge in GluN2 A KO mice resulted in unchanged PSA-NCAM levels and proBDNF increase in both brain structures as well as in increase in BDNF levels in hippocampus. Furthermore, the absence of GluN2 A resulted in increased levels of all NCAM isoforms in PFC upon LPS which was followed with a decrease in GluN1 and GluN2B subunits. The levels of AMPA receptor subunits (GluA1, GluA3, and GluA4) in the hippocampus of GluN2 A mice were unaltered upon the treatment and abundantly present in the PFC of KO mice. These results indicate that the GluN2 A subunit is critical in neuroinflammation-related depression, that its absence abolishes LPS-induced depressive phenotype, sustains PSA-NCAM levels, increases proBDNF signalling in the PFC and hippocampus and potentiates synaptic stabilization through NCAM in the PFC upon an immune challenge. © 2018 Elsevier B.V.",
journal = "Behavioural Brain Research",
title = "Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression",
volume = "359",
pages = "550-559",
doi = "10.1016/j.bbr.2018.10.011"
}
Francija, E., Petrović, Z., Brkić, Ž., Mitić, M., Radulović, J.,& Adžić, M.. (2019). Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression. in Behavioural Brain Research, 359, 550-559.
https://doi.org/10.1016/j.bbr.2018.10.011
Francija E, Petrović Z, Brkić Ž, Mitić M, Radulović J, Adžić M. Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression. in Behavioural Brain Research. 2019;359:550-559.
doi:10.1016/j.bbr.2018.10.011 .
Francija, Ester, Petrović, Zorica, Brkić, Željka, Mitić, Miloš, Radulović, Jelena, Adžić, Miroslav, "Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression" in Behavioural Brain Research, 359 (2019):550-559,
https://doi.org/10.1016/j.bbr.2018.10.011 . .
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