59621b9a7b4f08bf5a6d659e45543348 pmc_33668817.pdf 334793b54113503fa9785dd8d63ed661b5cecc67 pmc_33668817.pdf f3437529930d8d571984ba2b1a17048c9bb22581bc89fe6237ea04272438252d pmc_33668817.pdf Title: Cannabis Use Induces Distinctive Proteomic Alterations in Olfactory Neuroepithelial Cells of Schizophrenia Patients Subject: A close epidemiological link has been reported between cannabis use and schizophrenia (SCZ). However, biochemical markers in living humans related to the impact of cannabis in this disease are still missing. Olfactory neuroepithelium (ON) cells express neural features and offer a unique advantage to study biomarkers of psychiatric diseases. The aim of our study was to find exclusively deregulated proteins in ON cells of SCZ patients with and without a history of cannabis use. Thus, we compared the proteomic profiles of SCZ non-cannabis users (SCZ/nc) and SCZ cannabis users (SCZ/c) with control subjects non-cannabis users (C/nc) and control cannabis users (C/c). The results revealed that the main cascades affected in SCZ/nc were cell cycle, DNA replication, signal transduction and protein localization. Conversely, cannabis use in SCZ patients induced specific alterations in metabolism of RNA and metabolism of proteins. The levels of targeted proteins in each population were then correlated with cognitive performance and clinical scores. In SCZ/c, the expression levels of 2 proteins involved in the metabolism of RNA (MTREX and ZNF326) correlated with several cognitive markers and clinical signs. Moreover, use duration of cannabis negatively correlated with ZNF326 expression. These findings indicate that RNA-related proteins might be relevant to understand the influence of cannabis use on SCZ. Keywords: cannabis; schizophrenia; proteomics; olfactory neuroepithelium; metabolism; RNA; ZNF326; MTREX Author: Marta Barrera-Conde, Karina Ausin, Mercedes Lachén-Montes, Joaquín Fernández-Irigoyen, Liliana Galindo, Aida Cuenca-Royo, Cristina Fernández-Avilés, Víctor Pérez, Rafael de la Torre, Enrique Santamaría and Patricia Robledo Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Mar 12 06:18:35 2021 CET ModDate: Fri Mar 12 06:20:46 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1612361 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BOMHEM+VnURWPalladioL Type 1 Custom yes yes no 10 0 WZUXEG+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 EUWGAM+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 HWULGZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 UIJACC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 84 0 FFDGWE+CMSY10 Type 1 Builtin yes yes no 88 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 92 0 EUQOAW+EURM7 Type 1 Builtin yes yes no 102 0 PBFCOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 116 0 PBFCON+PalatinoLinotype TrueType WinAnsi yes yes no 119 0 PBFCOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 122 0 PBFCOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 139 0 PBFCOM+PalatinoLinotype CID TrueType Identity-H yes yes yes 142 0 PBFCON+PalatinoLinotype TrueType WinAnsi yes yes no 148 0 PBFCOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 151 0 PBFCOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 166 0 PBFCOM+PalatinoLinotype CID TrueType Identity-H yes yes yes 169 0 PBFCON+PalatinoLinotype TrueType WinAnsi yes yes no 175 0 PBFCOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 178 0 PBFCOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 193 0 PBFCON+PalatinoLinotype TrueType WinAnsi yes yes no 196 0 PBFCOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 199 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:28:57 CEST RepresentationInformation: pmc_33668817.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:03 CEST Size: 1612361 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 418 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design Destination: subsection.2.1 Item: Title: Clinical and Neuropsychological Evaluation Destination: subsection.2.2 Item: Title: Quantification of Cannabis Metabolites Destination: subsection.2.3 Item: Title: Nasal Exfoliation and Cell Culture Destination: subsection.2.4 Item: Title: Quantitative Proteomics in ON Cells Destination: subsection.2.5 Item: Title: Pathway Analysis, Statistics and Bioinformatics Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Demographics and Neuropsychological Outcomes Destination: subsection.3.1 Item: Title: Plasmatic Concentrations of THC-COOH Destination: subsection.3.2 Item: Title: Proteomic Analyses Destination: subsection.3.3 Children: Item: Title: Quantitative and Functional Proteomic Profile of ON Cells from SCZ Patients as Compared to C/nc Destination: subsubsection.3.3.1 Item: Title: Quantitative and Functional Proteomic Profile of ON Cells from SCZ Patients as Compared to C/nc Destination: subsubsection.3.3.2 Item: Title: Specific Proteins Markers of SCZ Depending on Cannabis Use Destination: subsubsection.3.3.3 Item: Title: Correlations between Specific Protein Markers, Cannabis Use and Cognitive Performance Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Cannabis Use Induces Distinctive Proteomic Alterations in Olfactory Neuroepithelial Cells of Schizophrenia Patients Author: Marta Barrera-Conde, Karina Ausin, Mercedes Lachén-Montes, Joaquín Fernández-Irigoyen, Liliana Galindo, Aida Cuenca-Royo, Cristina Fernández-Avilés, Víctor Pérez, Rafael de la Torre, Enrique Santamaría and Patricia Robledo Subject: A close epidemiological link has been reported between cannabis use and schizophrenia (SCZ). However, biochemical markers in living humans related to the impact of cannabis in this disease are still missing. Olfactory neuroepithelium (ON) cells express neural features and offer a unique advantage to study biomarkers of psychiatric diseases. The aim of our study was to find exclusively deregulated proteins in ON cells of SCZ patients with and without a history of cannabis use. Thus, we compared the proteomic profiles of SCZ non-cannabis users (SCZ/nc) and SCZ cannabis users (SCZ/c) with control subjects non-cannabis users (C/nc) and control cannabis users (C/c). The results revealed that the main cascades affected in SCZ/nc were cell cycle, DNA replication, signal transduction and protein localization. Conversely, cannabis use in SCZ patients induced specific alterations in metabolism of RNA and metabolism of proteins. The levels of targeted proteins in each population were then correlated with cognitive performance and clinical scores. In SCZ/c, the expression levels of 2 proteins involved in the metabolism of RNA (MTREX and ZNF326) correlated with several cognitive markers and clinical signs. Moreover, use duration of cannabis negatively correlated with ZNF326 expression. These findings indicate that RNA-related proteins might be relevant to understand the influence of cannabis use on SCZ. 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