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Coneixement","award":["FCRB_PB_2018"],"award-info":[{"award-number":["FCRB_PB_2018"]}]},{"name":"Government of Catalonia, Secretaria d\u2019Universitats i Recerca del Departament d\u2019Economia i Coneixement","award":["2017SGR1562"],"award-info":[{"award-number":["2017SGR1562"]}]},{"name":"Government of Catalonia, Secretaria d\u2019Universitats i Recerca del Departament d\u2019Economia i Coneixement","award":["2017SGR1355"],"award-info":[{"award-number":["2017SGR1355"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24021022","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T04:51:31Z","timestamp":1672894291000},"page":"1022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2835-9678","authenticated-orcid":false,"given":"Nina","family":"Treder","sequence":"first","affiliation":[{"name":"Faculty of Psychology and Neuroscience, Maastricht University, 6211 LK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2035-5979","authenticated-orcid":false,"given":"Albert","family":"Mart\u00ednez-Pinte\u00f1o","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Department of Basic and Clinical Practice, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Department of Basic and Clinical Practice, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Clinical and Experimental Neuroscience Area, The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00e9stor","family":"Arbelo","sequence":"additional","affiliation":[{"name":"Barcelona Cl\u00ednic Schizophrenia Unit, Institute of Neuroscience, Hospital Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-4211","authenticated-orcid":false,"given":"Santiago","family":"Madero","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Neuroscience Area, The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Barcelona Cl\u00ednic Schizophrenia Unit, Institute of Neuroscience, Hospital Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"},{"name":"G04 Group, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Neuroscience Area, The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"G04 Group, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Hospital \u00c1lvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (SERGAS), 36312 Vigo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Galicia Sur (IISGS), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4855-1608","authenticated-orcid":false,"given":"Clemente","family":"Garc\u00eda-Rizo","sequence":"additional","affiliation":[{"name":"Barcelona Cl\u00ednic Schizophrenia Unit, Institute of Neuroscience, Hospital Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"},{"name":"G04 Group, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Mas","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Department of Basic and Clinical 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Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0140-6736(15)01121-6","article-title":"Schizophrenia","volume":"388","author":"Owen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/schbul\/sbv119","article-title":"Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes: Table 1","volume":"42","author":"Edwards","year":"2015","journal-title":"Schizophr. 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