caa a22 4500 60620251X CHVBK 20210128100953.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00429-014-0779-8 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0779-8 Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice [Elektronische Daten] [Maryam Ghafari, Nigel Whittle, András Miklósi, Caroline Kotlowsky, Claudia Schmuckermair, Johannes Berger, Keiryn Bennett, Nicolas Singewald, Gert Lubec] Reduced daily intake of magnesium (Mg2+) is suggested to contribute to depression. Indeed, preclinical studies show dietary magnesium restriction (MgR) elicits enhanced depression-like behaviour establishing a causal relationship. Amongst other mechanisms, Mg2+ gates the activity of N-methyl-d-asparte (NMDA) receptors; however, it is not known whether reduced dietary Mg2+ intake can indeed affect brain NMDA receptor complexes. Thus, the aim of the current study was to reveal whether MgR induces changes in brain NMDA receptor subunit composition that would indicate altered NMDA receptor regulation. The results revealed that enhanced depression-like behaviour elicited by MgR was associated with reduced amygdala-hypothalamic protein levels of GluN1-containing NMDA complexes. No change in GluN1 mRNA levels was observed indicating posttranslational changes were induced by dietary Mg2+ restriction. To reveal possible protein interaction partners, GluN1 immunoprecipitation and proximity ligation assays were carried out revealing the expected GluN1 subunit association with GluN2A, GluN2B, but also novel interactions with GluA1, GluA2 in addition to known downstream signalling proteins. Chronic paroxetine treatment in MgR mice normalized enhanced depression-like behaviour, but did not alter protein levels of GluN1-containing NMDA receptors, indicating targets downstream of the NMDA receptor. Collectively, present data demonstrate that dietary MgR alters brain levels of GluN1-containing NMDA receptor complexes, containing GluN2A, GluN2B, AMPA receptors GluA1, GluA2 and several protein kinases. These data indicate that the modulation of dietary Mg2+ intake may alter the function and signalling of this receptor complex indicating its involvement in the enhanced depression-like behaviour elicited by MgR. Springer-Verlag Berlin Heidelberg, 2014 NMDA nationallicence Receptor complexes nationallicence Dietary magnesium restriction nationallicence Depression nationallicence Forced swim test nationallicence Amygdala nationallicence Hypothalamus nationallicence Ghafari Maryam Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut Whittle Nigel Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr Straße 1/1 Stock, 6020, Innsbruck, Austria aut Miklósi András Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut Kotlowsky Caroline Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut Schmuckermair Claudia Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr Straße 1/1 Stock, 6020, Innsbruck, Austria aut Berger Johannes Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria aut Bennett Keiryn CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH Building BT 25.3, 1090, Vienna, Austria aut Singewald Nicolas Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr Straße 1/1 Stock, 6020, Innsbruck, Austria aut Lubec Gert Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2209-2221 1863-2653 220:4<2209 2015 220 429 https://doi.org/10.1007/s00429-014-0779-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0779-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ghafari Maryam Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Whittle Nigel Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr Straße 1/1 Stock, 6020, Innsbruck, Austria aut NATIONALLICENCE 700 1- Miklósi András Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Kotlowsky Caroline Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Schmuckermair Claudia Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr Straße 1/1 Stock, 6020, Innsbruck, Austria aut NATIONALLICENCE 700 1- Berger Johannes Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Bennett Keiryn CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH Building BT 25.3, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Singewald Nicolas Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr Straße 1/1 Stock, 6020, Innsbruck, Austria aut NATIONALLICENCE 700 1- Lubec Gert Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2209-2221 1863-2653 220:4<2209 2015 220 429