title: MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients.
abstract: Schizophrenia is a common neuropsychiatric disorder that has a strong genetic component. MicroRNAs (miRNAs) have been implicated in neurodevelopmental and psychiatric disorders including schizophrenia, as indicated by their dysregulation in post-mortem brain tissues and in peripheral blood of schizophrenia patients. The olfactory epithelium (OE) is one of the few accessible neural tissues that contain neurons and their stem cells. Previous studies showed that OE-derived tissues and cells can be safely and easily collected from live human subjects and may provide a "window" into neuronal processes involved in disorders such as schizophrenia, while avoiding the limitations of using postmortem brain samples or non-neuronal tissues. In this study, we found that the brain-enriched miR-382 (miR-382-5p) expression was elevated in in vitro cultured olfactory cells, in a cohort of seven schizophrenia patients compared with seven non-schizophrenic controls. MiR-382 elevation was further confirmed in laser-capture microdissected OE neuronal tissue (LCM-OE), enriched for mature olfactory neurons, in a cohort of 18 schizophrenia patients and 18 non-schizophrenic controls. In sharp contrast, miR-382 expression could not be detected in lymphoblastoid cell lines generated from schizophrenic or non-schizophrenic individuals. We further found that miR-382 directly regulates the expression of two genes, FGFR1 and SPRY4, which are downregulated in both the cultured olfactory cells and LCM-OE derived from schizophrenia patients. These genes are involved in the fibroblast growth factor (FGF) signaling pathway, while impairment of this pathway may underlie abnormal brain development and function associated with schizophrenia. Our data suggest that miR-382 elevation detected in patients' OE-derived samples might serve to strengthen current biomarker studies in schizophrenia. This study also illustrates the potential utility of OE-derived tissues and cells as surrogate samples for the brain.
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. eyalmor@post.tau.ac.il
authors.forename: Eyal
authors.initials: E
authors.lastname: Mor
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Kano
authors.forename: Carlo
authors.initials: C
authors.lastname: Colantuoni
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.forename: Ruth
authors.initials: R
authors.lastname: Navon
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D061346:Laser Capture Microdissection; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000473:pathology*; D011180:Postmortem Changes; D012559:Schizophrenia / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C555413:MIRN382 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C499038:SPRY4 protein, human; D005346:Fibroblast Growth Factors
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