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Title: | Early treatment with JNJ-46356479, a mGluR2 modulator, improves behavioral and neuropathological deficits in a postnatal ketamine mouse model of schizophrenia. |
Author: | Martínez Pinteño, Albert Rodríguez Ferret, Natalia Olivares, David Madero, Santiago Gómez, M Prohens, Llucia García Rizo, Clemente Mas Herrero, Sergi Morén Núñez, Constanza Parellada Rodón, Eduard Gassó Astorga, Patricia |
Keywords: | Esquizofrènia Antipsicòtics Ratolins (Animals de laboratori) Ús terapèutic Enzims al·lostèrics Schizophrenia Antipsychotic drugs Mice (Laboratory animals) Therapeutic use Allosteric enzymes |
Issue Date: | 14-Dec-2022 |
Publisher: | Elsevier Masson SAS |
Abstract: | Positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), may mitigate the glutamate storm during the early stages of schizophrenia (SZ), which could be especially useful in the treatment of cognitive and negative symptoms. We evaluated the efficacy of early treatment with JNJ or clozapine (CLZ) in reversing behavioral and neuropathological deficits induced in a postnatal ketamine (KET) mouse model of SZ. Mice exposed to KET (30 mg/kg) on postnatal days (PND) 7, 9, and 11 received JNJ or CLZ (10 mg/kg) daily in the adolescent period (PND 35-60). Mice exposed to KET did not show the expected preference for a novel object or for social novelty, but they recovered this preference with JNJ treatment. Similarly, KET group did not show the expected dishabituation in the fifth trial, but mice treated with JNJ or CLZ recovered an interest in the novel animal. Neuronal immunoreactivity also differed between treatment groups with mice exposed to KET showing a reduction in parvalbumin positive cells in the prefrontal cortex and decreased c-Fos expression in the hippocampus, which was normalized with the pharmacological treatment. JNJ-46356479 treatment in early stages may help improve the cognitive and negative symptoms, as well as certain neuropathological deficits, and may even obtain a better response than CLZ treatment. This may have relevant clinical translational applications since early treatment with mGluR2 modulators that inhibit glutamate release at the onset of critical phases of SZ may prevent or slow down the clinical deterioration of the disease. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.biopha.2022.114079 |
It is part of: | Biomedicine & Pharmacotherapy, 2023, vol. 24, num. 2, p. 1022 |
URI: | http://hdl.handle.net/2445/196070 |
Related resource: | https://doi.org/10.1016/j.biopha.2022.114079 |
ISSN: | 0753-3322 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
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