Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and f...

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Main Authors: Andrés Rodríguez-Vega, Ana Carolina Dutra-Tavares, Thainá P. Souza, Keila A. Semeão, Claudio C. Filgueiras, Anderson Ribeiro-Carvalho, Alex C. Manhães, Yael Abreu-Villaça
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/19/14634
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author Andrés Rodríguez-Vega
Ana Carolina Dutra-Tavares
Thainá P. Souza
Keila A. Semeão
Claudio C. Filgueiras
Anderson Ribeiro-Carvalho
Alex C. Manhães
Yael Abreu-Villaça
author_facet Andrés Rodríguez-Vega
Ana Carolina Dutra-Tavares
Thainá P. Souza
Keila A. Semeão
Claudio C. Filgueiras
Anderson Ribeiro-Carvalho
Alex C. Manhães
Yael Abreu-Villaça
author_sort Andrés Rodríguez-Vega
collection DOAJ
description Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.
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spelling doaj.art-a14efd93d14f4afa95a60e273a0716fd2023-11-19T14:29:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191463410.3390/ijms241914634Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent MiceAndrés Rodríguez-Vega0Ana Carolina Dutra-Tavares1Thainá P. Souza2Keila A. Semeão3Claudio C. Filgueiras4Anderson Ribeiro-Carvalho5Alex C. Manhães6Yael Abreu-Villaça7Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilLaboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilLaboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilLaboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilLaboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilDepartamento de Ciências, Faculdade de Formação de Professores da Universidade do Estado do Rio de Janeiro, São Gonçalo 24435-005, RJ, BrazilLaboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilLaboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, BrazilTobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.https://www.mdpi.com/1422-0067/24/19/14634psychiatric disordernicotine addictionproteomeE-cigarettemass spectrometryprodrome
spellingShingle Andrés Rodríguez-Vega
Ana Carolina Dutra-Tavares
Thainá P. Souza
Keila A. Semeão
Claudio C. Filgueiras
Anderson Ribeiro-Carvalho
Alex C. Manhães
Yael Abreu-Villaça
Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
International Journal of Molecular Sciences
psychiatric disorder
nicotine addiction
proteome
E-cigarette
mass spectrometry
prodrome
title Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
title_full Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
title_fullStr Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
title_full_unstemmed Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
title_short Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
title_sort nicotine exposure in a phencyclidine induced mice model of schizophrenia sex selective medial prefrontal cortex protein markers of the combined insults in adolescent mice
topic psychiatric disorder
nicotine addiction
proteome
E-cigarette
mass spectrometry
prodrome
url https://www.mdpi.com/1422-0067/24/19/14634
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