Cre-activation in ErbB4-positive neurons of floxed Grin1/NMDA receptor mice is not associated with major behavioral impairment

• Verfasst von: Mallien, Anne Stephanie [VerfasserIn]
• Verfasst von: Pfeiffer, Natascha [VerfasserIn]
• Verfasst von: Vogt, Miriam A. [VerfasserIn]
• Verfasst von: Chourbaji, Sabine [VerfasserIn]
• Verfasst von: Sprengel, Rolf [VerfasserIn]
• Verfasst von: Gass, Peter [VerfasserIn]
• Verfasst von: Inta, Dragos [VerfasserIn]
• Titel: Cre-activation in ErbB4-positive neurons of floxed Grin1/NMDA receptor mice is not associated with major behavioral impairment
• Verf.angabe: Anne S. Mallien, Natascha Pfeiffer, Miriam A. Vogt, Sabine Chourbaji, Rolf Sprengel, Peter Gass and Dragos Inta
• E-Jahr: 2021
• Jahr: 25 November 2021
• Umfang: 11 S.
• Fussnoten: Gesehen am 16.12.2021
• Titel Quelle: Enthalten in: Frontiers in psychiatry
• Ort Quelle: Lausanne : Frontiers Research Foundation, 2007
• Jahr Quelle: 2021
• Band/Heft Quelle: 12(2021) vom: 25. Nov., Artikel-ID 750106, Seite 1-11
• ISSN Quelle: 1664-0640
• DOI: doi:10.3389/fpsyt.2021.750106
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1782369821
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Extensive evidence suggests a dysfunction of the glutamate NMDA receptor (NMDAR) in schizophrenia, a severe psychiatric disorder with putative early neurodevelopmental origins, but clinical onset mainly during late adolescence. On the other hand, pharmacological models using NMDAR antagonists and the clinical manifestation of anti-NMDAR encephalitis indicate that NMDAR blockade/hypofunction can trigger psychosis also at adult stages, without any early developmental dysfunction. Previous genetic models of NMDAR hypofunction restricted to parvalbumin-positive interneurons indicate the necessity of an early postnatal impairment to trigger schizophrenia-like abnormalities, whereas the cellular substrates of NMDAR-mediated psychosis at adolescent/adult stages are unknown. Neuregulin 1 (NRG1) and its receptor ErbB4 represent schizophrenia-associated susceptibility factors that closely interact with NMDAR. To determine the neuronal populations implicated in “late” NMDAR-driven psychosis, we analyzed the effect of the inducible ablation of NMDARs in ErbB4-expressing cells in mice during late adolescence using a pharmacogenetic approach. Interestingly, the tamoxifen-inducible NMDAR deletion during this late developmental stage did not induce behavioral alterations resembling depression, schizophrenia or anxiety. Our data indicate that post-adolescent NMDAR deletion, even in a wider cell population than parvalbumin-positive interneurons, is also not sufficient to generate behavioral abnormalities resembling psychiatric disorders. Other neuronal substrates that have to be revealed by future studies, may underlie post-adolescent NMDAR-driven psychosis.