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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Published in:International journal of molecular sciences 2023-10, Vol.24 (19), p.14634
Main Authors: Rodríguez-Vega, Andrés, Dutra-Tavares, Ana Carolina, Souza, Thainá P, Semeão, Keila A, Filgueiras, Claudio C, Ribeiro-Carvalho, Anderson, Manhães, Alex C, Abreu-Villaça, Yael
Format: Article
Language:English
Subjects:
Addictive behaviors
Analysis
Antipsychotics
Child development
Comorbidity
E-cigarette
Gender differences
Hypotheses
Instrument industry
Life expectancy
Males
mass spectrometry
Mental disorders
Metabolism
Nicotine
nicotine addiction
Oxidative stress
Pathophysiology
Peptides
Phencyclidine
Physiological aspects
prodrome
Proteins
proteome
psychiatric disorder
Psychosis
Psychotropic drugs
Schizophrenia
Tobacco
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241914634