title: Semaphorin and plexin gene expression is altered in the prefrontal cortex of schizophrenia patients with and without auditory hallucinations.
abstract: Auditory hallucinations (AH) are clinical hallmarks of schizophrenia, however little is known about molecular genetics of these symptoms. In this study, gene expression profiling of postmortem brain samples from prefrontal cortex of schizophrenic patients without AH (SNA), patients with AH (SA) and control subjects were compared. Genome-wide expression analysis was conducted using samples of three individuals of each group and the Affymetrix GeneChip Human-Gene 1.0 ST-Array. This analysis identified the Axon Guidance pathway as one of the most differentially expressed network among SNA, SA and CNT. To confirm the transcriptome results, mRNA level quantification of seventeen genes involved in this pathway was performed in a larger sample. PLXNB1, SEMA3A, SEMA4D and SEM6C were upregulated in SNA or SA patients compared to controls. PLXNA1 and SEMA3D showed down-regulation in their expression in the patient's samples, but differences remained statistically significant between the SNA patients and controls. Differences between SNA and SA were found in PLXNB1 expression which is decreased in SA patients. This study strengthens the contribution of brain plasticity in pathophysiology of schizophrenia and shows that non-hallucinatory patients present more alterations in frontal regions than patients with hallucinations concerning neural plasticity.
authors.affiliation: CIBERSAM, Spain; Departamento de Genética, Facultad de Biología, Universitat de València, INCLIVA, Valencia, Spain; Unidad de Neurobiología y Programa de Neurociencias Básicas y Aplicadas, Departamento de Biología Celular, Universitat de València, INCLIVA, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gilabert-Juan
authors.affiliation: Departamento de Genética, Facultad de Biología, Universitat de València, INCLIVA, Valencia, Spain.
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Sáez
authors.affiliation: Health and Biomedical Centre, The University of Melbourne, Australia.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lopez-Campos
authors.affiliation: Departamento de Genética, Facultad de Biología, Universitat de València, INCLIVA, Valencia, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Sebastiá-Ortega
authors.affiliation: Departamento de Genética, Facultad de Biología, Universitat de València, INCLIVA, Valencia, Spain; Unidad de Neurobiología y Programa de Neurociencias Básicas y Aplicadas, Departamento de Biología Celular, Universitat de València, INCLIVA, Valencia, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: González-Martínez
authors.affiliation: Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Deu, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Costa
authors.affiliation: CIBERSAM, Spain; Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Deu, Barcelona, Spain.
authors.forename: Josep María
authors.initials: JM
authors.lastname: Haro
authors.affiliation: CIBERSAM, Spain; Departamento de Farmacología, Universidad del País Vasco/Euskal Herriko Unibertsitatea UPV/EHU, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.affiliation: CIBERSAM, Spain; Departamento de Farmacología, Universidad del País Vasco/Euskal Herriko Unibertsitatea UPV/EHU, Spain; BioCruces Health Research Institute, Spain.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.affiliation: CIBERSAM, Spain; Unidad de Neurobiología y Programa de Neurociencias Básicas y Aplicadas, Departamento de Biología Celular, Universitat de València, INCLIVA, Valencia, Spain.
authors.forename: Juán
authors.initials: J
authors.lastname: Nacher
authors.affiliation: CIBERSAM, Spain; Hospital Clínico de Valencia, Universitat de València INCLIVA, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Sanjuán
authors.affiliation: CIBERSAM, Spain; Departamento de Genética, Facultad de Biología, Universitat de València, INCLIVA, Valencia, Spain. Electronic address: dmolto@uv.es.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Moltó
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons; D001921:Brain / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006212:Hallucinations / Q000235:genetics* / Q000523:psychology; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications / Q000235:genetics*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D039961:Semaphorins; C091529:plexin
keywords: Auditory hallucinations; Gene expression; Plexins; Prefrontal cortex; Schizophrenia; Semaphorins