title: Altered CSNK1E, FABP4 and NEFH protein levels in the dorsolateral prefrontal cortex in schizophrenia.
abstract: Schizophrenia constitutes a complex disease. Negative and cognitive symptoms are enduring and debilitating components of the disorder, highly associated to disability and burden. Disrupted neurotransmission circuits in dorsolateral prefrontal cortex (DLPFC) have been related to these symptoms. To identify candidates altered in schizophrenia, we performed a pilot proteomic analysis on postmortem human DLPFC tissue from patients with schizophrenia (n=4) and control (n=4) subjects in a pool design using differential isotope peptide labelling followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). We quantified 1315 proteins with two or more unique peptides, 116 of which showed altered changes. Of these altered proteins, we selected four with potential roles on cell signaling, neuronal development and synapse functioning for further validation: casein kinase I isoform epsilon (CSNK1E), fatty acid-binding protein 4 (FABP4), neurofilament triplet H protein (NEFH), and retinal dehydrogenase 1 (ALDH1A1). Immunoblot validation confirmed our proteomic findings of these proteins being decreased in abundance in the schizophrenia samples. Additionally, we conducted immunoblot validation of these candidates on an independent sample cohort comprising 23 patients with chronic schizophrenia and 23 matched controls. In this second cohort, CSNK1E, FABP4 and NEFH were reduced in the schizophrenia group while ALDH1A1 did not significantly change. This study provides evidence indicating these proteins are decreased in schizophrenia: CSNK1E, involved in circadian molecular clock signaling, FABP4 with possible implication in synapse functioning, and NEFH, important for cytoarchitecture organization. Hence, these findings suggest the possible implication of these proteins in the cognitive and/or negative symptoms in schizophrenia.
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Pinacho
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Villalmanzo
authors.affiliation: Departamento de Farmacología, Universidad del País Vasco/Euskal Herriko Unibertsitatea UPV/EHU, Instituto BioCruces, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Bº Sarriena s/n, 48940 Leioa, Bizkaia, Spain.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.affiliation: Instituto de Neuropatología, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Centro de Investigación Biomédica en Red para enfermedades neurodegenerativas, CIBERNED, Feixa Llarga s/n, Hospitalet de LLobregat, 08907 Barcelona, Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Banc de Teixits Neurologics, Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Berengueras
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Haro
authors.affiliation: Genome Sciences Department, School of Medicine, University of Washington, 3720 15th Ave NE, Seattle 98195, WA, USA.
authors.forename: Judit
authors.initials: J
authors.lastname: Villén
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain. Electronic address: bramos@fsjd.org.
authors.forename: Belén
authors.initials: B
authors.lastname: Ramos
mesh_terms: D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D048149:Casein Kinase 1 epsilon / Q000378:metabolism*; D002853:Chromatography, Liquid; D015331:Cohort Studies; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism*; D010865:Pilot Projects; D017397:Prefrontal Cortex / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics; D050697:Retinal Dehydrogenase; D012559:Schizophrenia / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D016900:Neurofilament Proteins; D020543:Proteome; C051774:neurofilament protein H; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D048149:Casein Kinase 1 epsilon
keywords: CSNK1E; FABP4; NEFH; Postmortem dorsolateral prefrontal cortex; Proteomics; Schizophrenia