MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients

Eyal Mor, Shin Ichi Kano, Carlo Colantuoni, Akira Sawa*, Ruth Navon, Noam Shomron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalNeurobiology of Disease
Volume55
DOIs
StatePublished - Jul 2013

Funding

FundersFunder number
JHU-BSI
US National Institutes of HealthK99MH093458
National Institutes of HealthMH-084018, MH-94268, MH-092443, MH-069853, MH-088753
National Institute of Mental HealthR21MH085226
National Alliance for Research on Schizophrenia and Depression
Maryland Stem Cell Research Fund
Chief Scientist Office
Japan Society for the Promotion of Science
Israel Cancer Association
Israel Science Foundation41/11
Ministry of Health, State of Israel3-4876
Wolfson Family Charitable Trust

    Keywords

    • MiRNA
    • MicroRNA
    • Olfactory epithelium
    • Olfactory neuroepithelium
    • Schizophrenia

    Fingerprint

    Dive into the research topics of 'MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients'. Together they form a unique fingerprint.

    Cite this