Olfactory neural cells have recently been developed as a novel cell-based model of psychiatric disorder. These primary neural cells can be established from nasal biopsies, making them the only source of live patient neural material that can be obtained directly from patients. Though olfactory neural progenitor cells (ONPs) cannot generate all the neural lineages specifically implicated in schizophrenia, they differentiate to mature electrophysiologically active neurons, making them an exciting platform to test for genetic neural defects present in schizophrenia (Benitez-King et al., 2011). ONPs from patients with schizophrenia and controls have altered cell cycle dynamics (Fan et al., 2012) as well as differences in gene expression of neurodevelopmental pathways associated with cell migration and axon guidance (Matigian et al., 2010).

In their letter to the editor at Molecular Psychiatry, Kano et al. compare H3K4me3 and H3K27me3 CHIP-seq datasets and microarray gene expression profiles of olfactory cells from four controls and four patients with schizophrenia. Their analysis found a surprisingly small degree of overlap between the CHIP-seq and microarray data, identifying just 22 genes and 72 gene groups with significant correlations between the datasets. Nonetheless, genes in the category of "Phase 2 detoxification" were significantly altered in the schizophrenia group compared with normal controls in both analyses, suggesting a role for oxidative stress in schizophrenia. This is consistent with a recent study of induced pluripotent stem cell-derived neurons showing altered oxygen metabolism in neurons derived from a patient with schizophrenia (Paulsen et al., 2011). This is an interesting observation warranting follow-up on a larger cohort of patients.

References:

Benítez-King G, Riquelme A, Ortíz-López L, Berlanga C, Rodríguez-Verdugo MS, Romo F, Calixto E, Solís-Chagoyán H, Jímenez M, Montaño LM, Ramírez-Rodríguez G, Morales-Mulia S, Domínguez-Alonso A. A non-invasive method to isolate the neuronal linage from the nasal epithelium from schizophrenic and bipolar diseases. J Neurosci Methods . 2011 Sep 30 ; 201(1):35-45. Abstract

Fan Y, Abrahamsen G, McGrath JJ, Mackay-Sim A. Altered cell cycle dynamics in schizophrenia. Biol Psychiatry . 2012 Jan 15 ; 71(2):129-35. Abstract

Matigian N, Abrahamsen G, Sutharsan R, Cook AL, Vitale AM, Nouwens A, Bellette B, An J, Anderson M, Beckhouse AG, Bennebroek M, Cecil R, Chalk AM, Cochrane J, Fan Y, Féron F, McCurdy R, McGrath JJ, Murrell W, Perry C, Raju J, Ravishankar S, Silburn PA, Sutherland GT, Mahler S, Mellick GD, Wood SA, Sue CM, Wells CA, Mackay-Sim A. Disease-specific, neurosphere-derived cells as models for brain disorders. Dis Model Mech . 2010 Nov-Dec ; 3(11-12):785-98. Abstract

Paulsen BD, Maciel RD, Galina A, da Silveira MS, Souza CD, Drummond H, Pozzato EN, Junior HS, Chicaybam L, Massuda R, Setti-Perdigão P, Bonamino M, Belmonte-de-Abreu PS, Castro NG, Brentani H, Rehen SK. Altered oxygen metabolism associated to neurogenesis of induced pluripotent stem cells derived from a schizophrenic patient. Cell Transplant . 2011 Sep 22. Abstract

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