Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research

Abstract

Purpose of review The goal of this review article is to introduce olfactory epithelium (OE)-derived cell/tissue models as a promising surrogate system to study the molecular mechanisms implicated in schizophrenia (SZ) and other neuropsychiatric disorders. Here we particularly focus the utility of their neural progenitors. Recent findings Recent investigations of the pathophysiology of SZ using OE-derived tissue/cell models have provided insights about SZ-associated alterations in neurodevelopment, stress response, and gene/protein expression regulatory pathways. Summary The OE retains the capacity for lifelong neurogenesis and regeneration, because of the presence of neural stem cells and progenitors. Thus, both mature neurons and neural progenitors can be obtained from the OE without the need for genetic reprogramming and related confounds. Furthermore, the OE is highly scalable resource in translational settings. Here we also demonstrate recent findings from research using OE-derived tissue/cell models in SZ and other brain disorders. In summary, we propose that the OE as a promising resource to study neural molecular and cellular signatures relevant to the pathology of SZ and other mental disorders.

Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells from Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy

“…Thanks to their low invasiveness and high scalability, ON cell models have been put forward as promising surrogates to explore neuronal biomarkers in SCZ, providing a unique opportunity to unveil novel potential molecular targets for diagnosis and treatment [19]. To our knowledge, this is the first study applying SR-FTIR spectroscopy in ON cells to study the macromolecular alterations in SCZ.…”

“…Obtaining viable neurological tissue to study how biomarkers of disease are modulated by drugs such as cannabis in living patients has proven challenging. In this sense, the olfactory neuroepithelium (ON) has great potential as a surrogate model of central nervous system function to study the molecular processes involved in some neuropsychiatric disorders such as SCZ [19]. Human olfactory sensory neurons are replaced and generated by neurogenesis continuously, throughout all the adult life, from neuronal precursors located in the apical and basal membranes [20].…”

Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer’s disease from bioptic olfactory mucosa

“…Several previous studies support the notion that olfactory mucosa may reflect pathology of the central nervous system, e.g., in Parkinson's disease, schizophrenia, and rodent tauopathy models [26,31,39,42]. Interestingly, Moon et al found higher levels of miRNA-206 in olfactory mucosa in MCI and even more in manifest AD as compared to controls, thus supporting the suitability of olfactory mucosa tissue as a possible biomarker [30].…”

Epigenetic Modifications in Schizophrenia and Related Disorders: Molecular Scars of Environmental Exposures and Source of Phenotypic Variability

“…Addressing this question in the context of schizophrenia warrants the use of longitudinal studies in which epigenetic signatures can be followed-up in the same subjects from premorbid and high-risk states to the eventual onset of fullblown psychosis. Such longitudinal investigations, however, will require the use of easily accessible tissues such as peripheral blood, saliva, and olfactory epithelium (149). Even if epigenetic signatures in peripheral tissues might not necessarily capture disease-associated epigenetic changes occurring in the CNS (Tables 1 and 2), they can provide valuable information regarding the clinical course of schizophrenia, including conversion from a high-risk state to first-onset psychosis (50).…”