The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia

Schizophrenia (SZ) is a heterogeneous mental disorder, affecting ~1% of the worldwide population. One of the main pathophysiological theories of SZ is the imbalance of excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, involving N-methyl-D-aspartate receptors (NMDAr)....

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Autores: Treder, Nina, Martínez Pinteño, Albert, Rodríguez Ferret, Natalia, Arbelo, Néstor, Madero Gómez, Santiago, Gómez-Ramiro, Marta, García Rizo, Clemente, Mas Herrero, Sergi, Gassó Astorga, Patricia, Parellada Rodón, Eduard, Morén Núñez, Constanza
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/196071
Acceso en línea:https://hdl.handle.net/2445/196071
Access Level:acceso abierto
Palabra clave:Esquizofrènia
Ratolins (Animals de laboratori)
Escorça frontal
Farmacologia
Schizophrenia
Mice (Laboratory animals)
Prefrontal cortex
Pharmacology
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spelling The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of SchizophreniaTreder, NinaMartínez Pinteño, AlbertRodríguez Ferret, NataliaArbelo, NéstorMadero Gómez, SantiagoGómez-Ramiro, MartaGarcía Rizo, ClementeMas Herrero, SergiGassó Astorga, PatriciaParellada Rodón, EduardMorén Núñez, ConstanzaEsquizofrèniaRatolins (Animals de laboratori)Escorça frontalFarmacologiaSchizophreniaMice (Laboratory animals)Prefrontal cortexPharmacologySchizophrenia (SZ) is a heterogeneous mental disorder, affecting ~1% of the worldwide population. One of the main pathophysiological theories of SZ is the imbalance of excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, involving N-methyl-D-aspartate receptors (NMDAr). This may lead to local glutamate storms coupled with excessive dendritic pruning and subsequent cellular stress, including nitrosative stress, during a critical period of neurodevelopment, such as adolescence. Nitrosative stress is mediated by nitric oxide (NO), which is released by NO synthases (NOS) and has emerged as a key signaling molecule implicated in SZ. Regarding glutamatergic models of SZ, the administration of NMDAr antagonists has been found to increase NOS levels in the prefrontal cortex (PFC) and ventral hippocampus (HPC). We hypothesized that suboptimal NOS function in adolescence could be a target for early treatments, including clozapine (CLZ) and the novel metabotropic glutamate receptor modulator JNJ-46356479 (JNJ). We analyzed the protein levels of NOS isoforms in adult PFC and HPC of a postnatal ketamine induced murine model of SZ receiving CLZ or JNJ during adolescence by western blot. Endothelial NOS and neuronal NOS increased under ketamine administration in PFC and decreased in CLZ or JNJ treatments. The same trends were found in the HPC in neuronal NOS. In contrast, inducible NOS was increased under JNJ treatment with respect to ketamine induction in the HPC, and the same trends were found in the PFC. Taken together, our findings suggest a misbalance of the NOS system following NMDAr antagonist administration, which was then modulated under early CLZ and JNJ treatments.MDPI2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/196071Articles publicats en revistes (Fonaments Clínics)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms24021022International Journal of Molecular Sciences, 2023, vol. 24, num. 2, p. 1022https://doi.org/10.3390/ijms24021022cc-by (c) Treder, Nina et al., 2023https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1960712026-05-29T05:05:01Z
dc.title.none.fl_str_mv The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
title The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
spellingShingle The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
Treder, Nina
Esquizofrènia
Ratolins (Animals de laboratori)
Escorça frontal
Farmacologia
Schizophrenia
Mice (Laboratory animals)
Prefrontal cortex
Pharmacology
title_short The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
title_full The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
title_fullStr The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
title_full_unstemmed The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
title_sort The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia
dc.creator.none.fl_str_mv Treder, Nina
Martínez Pinteño, Albert
Rodríguez Ferret, Natalia
Arbelo, Néstor
Madero Gómez, Santiago
Gómez-Ramiro, Marta
García Rizo, Clemente
Mas Herrero, Sergi
Gassó Astorga, Patricia
Parellada Rodón, Eduard
Morén Núñez, Constanza
author Treder, Nina
author_facet Treder, Nina
Martínez Pinteño, Albert
Rodríguez Ferret, Natalia
Arbelo, Néstor
Madero Gómez, Santiago
Gómez-Ramiro, Marta
García Rizo, Clemente
Mas Herrero, Sergi
Gassó Astorga, Patricia
Parellada Rodón, Eduard
Morén Núñez, Constanza
author_role author
author2 Martínez Pinteño, Albert
Rodríguez Ferret, Natalia
Arbelo, Néstor
Madero Gómez, Santiago
Gómez-Ramiro, Marta
García Rizo, Clemente
Mas Herrero, Sergi
Gassó Astorga, Patricia
Parellada Rodón, Eduard
Morén Núñez, Constanza
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Esquizofrènia
Ratolins (Animals de laboratori)
Escorça frontal
Farmacologia
Schizophrenia
Mice (Laboratory animals)
Prefrontal cortex
Pharmacology
topic Esquizofrènia
Ratolins (Animals de laboratori)
Escorça frontal
Farmacologia
Schizophrenia
Mice (Laboratory animals)
Prefrontal cortex
Pharmacology
description Schizophrenia (SZ) is a heterogeneous mental disorder, affecting ~1% of the worldwide population. One of the main pathophysiological theories of SZ is the imbalance of excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, involving N-methyl-D-aspartate receptors (NMDAr). This may lead to local glutamate storms coupled with excessive dendritic pruning and subsequent cellular stress, including nitrosative stress, during a critical period of neurodevelopment, such as adolescence. Nitrosative stress is mediated by nitric oxide (NO), which is released by NO synthases (NOS) and has emerged as a key signaling molecule implicated in SZ. Regarding glutamatergic models of SZ, the administration of NMDAr antagonists has been found to increase NOS levels in the prefrontal cortex (PFC) and ventral hippocampus (HPC). We hypothesized that suboptimal NOS function in adolescence could be a target for early treatments, including clozapine (CLZ) and the novel metabotropic glutamate receptor modulator JNJ-46356479 (JNJ). We analyzed the protein levels of NOS isoforms in adult PFC and HPC of a postnatal ketamine induced murine model of SZ receiving CLZ or JNJ during adolescence by western blot. Endothelial NOS and neuronal NOS increased under ketamine administration in PFC and decreased in CLZ or JNJ treatments. The same trends were found in the HPC in neuronal NOS. In contrast, inducible NOS was increased under JNJ treatment with respect to ketamine induction in the HPC, and the same trends were found in the PFC. Taken together, our findings suggest a misbalance of the NOS system following NMDAr antagonist administration, which was then modulated under early CLZ and JNJ treatments.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/196071
url https://hdl.handle.net/2445/196071
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms24021022
International Journal of Molecular Sciences, 2023, vol. 24, num. 2, p. 1022
https://doi.org/10.3390/ijms24021022
dc.rights.none.fl_str_mv cc-by (c) Treder, Nina et al., 2023
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Treder, Nina et al., 2023
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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