AMPA GluR-A receptor subunit mediates hippocampal responsiveness in mice exposed to stress

Because stress represents a major precipitating event for psychiatric disorders, it is important to identify molecular mechanisms that may be altered in vulnerable individuals when exposed to stress. Here, we studied GluR-A−/− mice, animals with compromised AMPA receptor signaling, and characterized...

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Hauptverfasser: Fumagalli, Fabio (VerfasserIn) , Caffino, Lucia (VerfasserIn) , Vogt, Miriam A. (VerfasserIn) , Frasca, Angelisa (VerfasserIn) , Racagni, Giorgio (VerfasserIn) , Sprengel, Rolf (VerfasserIn) , Gass, Peter (VerfasserIn) , Riva, Marco Andrea (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 23. August 2011
In: Hippocampus
Year: 2011, Jahrgang: 21, Heft: 9, Pages: 1028-1035
ISSN:1098-1063
DOI:10.1002/hipo.20817
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/hipo.20817
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.20817
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Verfasserangaben:Fabio Fumagalli, Lucia Caffino, Miriam A. Vogt, Angelisa Frasca, Giorgio Racagni, Rolf Sprengel, Peter Gass, and Marco Andrea Riva
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Zusammenfassung:Because stress represents a major precipitating event for psychiatric disorders, it is important to identify molecular mechanisms that may be altered in vulnerable individuals when exposed to stress. Here, we studied GluR-A−/− mice, animals with compromised AMPA receptor signaling, and characterized by a schizophrenic as well as depressive phenotype to investigate changes occurring in response to an acute stress. Wild-type and GluR-A−/− mice were exposed to a single immobilization stress and sacrificed immediately after the end of the stress for the analysis of activity regulated genes and of glutamatergic synapse responsiveness. The acute stress produced a marked increase in the hippocampal expression of Arc (activity-regulated cytoskeletal-associated protein) in GluR-A−/−, but not in wild-type mice, which was associated with a similar increase of phospho-CaMKII, a partner in the action of Arc. When looking at the glutamatergic response to stress in wild-type animals, we found that stress increased GluR-A phosphorylation on serine831, an effect that was paralleled by a significant increase of the phosphorylation of the main NMDA receptor subunits, that is, NR-1 and NR-2B. Conversely, the stress-induced modulation of NMDA receptor subunits was not observed in GluR-A−/− mice. We suggest that enhanced stress responsiveness in GluR-A−/− mice may be due, at least in part, to their inability to activate NMDA-mediated glutamatergic neurotransmission, suggesting that the integrity of AMPA/NMDA receptor function may be important for successful coping under stressful conditions. © 2010 Wiley-Liss, Inc.
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Erscheinungsjahr im PDF: Online veröffentlicht am 22. Juni 2010, Urheberrecht: 2010 Wiley-Liss, Inc. ; Erscheinungsjahr auf der Frontdoor: Erstmals veröffentlicht: 23. August 2011
Beschreibung:Online Resource
ISSN:1098-1063
DOI:10.1002/hipo.20817