Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment

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 th...

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Autores principales:	Anne S. Mallien, Natascha Pfeiffer, Miriam A. Vogt, Sabine Chourbaji, Rolf Sprengel, Peter Gass, Dragos Inta
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glutamate neurodevelopment pharmacogenetic neuregulin-1 schizophrenia NMDA receptor Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/19540137975f4814a24a3945dde269df
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spelling	oai:doaj.org-article:19540137975f4814a24a3945dde269df2021-12-01T02:26:13ZCre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment1664-064010.3389/fpsyt.2021.750106https://doaj.org/article/19540137975f4814a24a3945dde269df2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fpsyt.2021.750106/fullhttps://doaj.org/toc/1664-0640Extensive 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.Anne S. MallienNatascha PfeifferMiriam A. VogtSabine ChourbajiRolf SprengelRolf SprengelPeter GassDragos IntaDragos IntaFrontiers Media S.A.articleglutamateneurodevelopmentpharmacogeneticneuregulin-1schizophreniaNMDA receptorPsychiatryRC435-571ENFrontiers in Psychiatry, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glutamate neurodevelopment pharmacogenetic neuregulin-1 schizophrenia NMDA receptor Psychiatry RC435-571
spellingShingle	glutamate neurodevelopment pharmacogenetic neuregulin-1 schizophrenia NMDA receptor Psychiatry RC435-571 Anne S. Mallien Natascha Pfeiffer Miriam A. Vogt Sabine Chourbaji Rolf Sprengel Rolf Sprengel Peter Gass Dragos Inta Dragos Inta Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment
description	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.
format	article
author	Anne S. Mallien Natascha Pfeiffer Miriam A. Vogt Sabine Chourbaji Rolf Sprengel Rolf Sprengel Peter Gass Dragos Inta Dragos Inta
author_facet	Anne S. Mallien Natascha Pfeiffer Miriam A. Vogt Sabine Chourbaji Rolf Sprengel Rolf Sprengel Peter Gass Dragos Inta Dragos Inta
author_sort	Anne S. Mallien
title	Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment
title_short	Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment
title_full	Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment
title_fullStr	Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment
title_full_unstemmed	Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment
title_sort	cre-activation in erbb4-positive neurons of floxed grin1/nmda receptor mice is not associated with major behavioral impairment
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/19540137975f4814a24a3945dde269df
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Cre-Activation in ErbB4-Positive Neurons of Floxed Grin1/NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment

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