Schizophrenia Research Forum - A Catalyst for Creative Thinking


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. Pubmed Abstract

Comments on News and Primary Papers


Primary Papers: A non-invasive method to isolate the neuronal linage from the nasal epithelium from schizophrenic and bipolar diseases.

Comment by:  Yasue HoriuchiAkira Sawa (SRF Advisor)Patricia Gassó Astorga
Submitted 22 August 2011
Posted 23 August 2011

We find significance in the recent paper from the Domínguez-Alonso’s group on “a non-invasive method to isolate the neuronal linage from the nasal epithelium from schizophrenic and bipolar diseases.” They developed a non-invasive method to obtain neural precursor cells from the nasal epithelium of human subjects, including patients with schizophrenia and bipolar disorder.

As many of us agree that, although autopsied brains are still very useful, we have some concerns in the confounding factors associated with the brains. In addition, to address neurodevelopment-associated changes that may underlie the pathology of schizophrenia and other mental illnesses, researchers have debated the usefulness of the autopsied brains.

To compromise these limitations, scientists have also considered use of biopsied tissues. A major breakthrough in the past couple of years is the development of new technologies of induced pluripotent stem cells (iPS cells) and induced neuronal cells (iN cells) in which we can generate neurons from peripheral tissues, especially skin fibroblasts (Takahashi et al., 2007; Pang et al., 2011). Our group is intensively applying these technologies with the use of our collections of the fibroblasts from patients with schizophrenia and bipolar disorder as well as normal controls. Nonetheless, a drawback of these technologies is an artificial conversion of cells by introducing exogenous genetic factors. Thus, a methodology to obtain neuronal cells without the introduction of any exogenous genetic factors is still important. In this sense, the paper by the Domínguez-Alonso group would be significant.

There are two major points to mention in this paper. Compared to the previous reports with the biopsied olfactory tissues (Borgmann-Winter et al., 2009; Matigian et al., 2010; Viktorov et al., 2007; Winstead et al., 2005), the methodology introduced here achieves enrichment of βIII-tubulin-positive cells (immature neuronal cells) to near homogeneity. We also appreciate the authors’ efforts to differentiate immature cells to mature neurons in this manuscript. Morphological and functional characterization, including calcium imaging, has been done in an extensive manner.

Nonetheless, a fundamental question to be addressed in all the studies of olfactory tissues and cells from patients is unanswered. Do these immature βIII-tubulin-positive neuronal cells and mature olfactory marker protein (OMP)-positive neurons really reflect the molecular signature of neurons that are affected in patients with mental illnesses? Although this study further enhances the potential of using olfactory neurons in translational psychiatry, it would be very important to address this question in order to know the real advantages and limitations of using olfactory cells in this research area.

References:

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell . 2007 Nov 30 ; 131(5):861-72. Abstract

Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M. Induction of human neuronal cells by defined transcription factors. Nature . 2011 Aug 11 ; 476(7359):220-3. Abstract

Borgmann-Winter KE, Rawson NE, Wang HY, Wang H, MacDonald ML, Ozdener MH, Yee KK, Gomez G, Xu J, Bryant B, Adamek G, Mirza N, Pribitkin E, Hahn CG. Human olfactory epithelial cells generated in vitro express diverse neuronal characteristics. Neuroscience . 2009 Jan 23 ; 158(2):642-53. 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

Viktorov IV, Savchenko EA, Chekhonin VP. Spontaneous neural differentiation of stem cells in culture of human olfactory epithelium. Bull Exp Biol Med . 2007 Oct 1 ; 144(4):596-601. Abstract

Winstead W, Marshall CT, Lu CL, Klueber KM, Roisen FJ. Endoscopic biopsy of human olfactory epithelium as a source of progenitor cells. Am J Rhinol . 2005 Jan-Feb ; 19(1):83-90. Abstract

View all comments by Yasue Horiuchi
View all comments by Akira Sawa
View all comments by Patricia Gassó Astorga