Human olfactory epithelial cells generated in vitro express diverse neuronal characteristics

Abstract

The olfactory epithelium constitutes the sole source of regenerating neural cells that can be obtained from a living human. As such, primary cultures derived from olfactory epithelial biopsies can be utilized to study neurobiological characteristics of individuals under different conditions and disease states. Here, using such cultures, we report in vitro generation of cells that exhibit a complex neuronal phenotype, encompassing receptors and signaling pathways pertinent to both olfaction and other aspects of CNS function. Using in situ hybridization, we demonstrate for the first time the native expression of olfactory receptors in cultured cells derived from olfactory epithelial tissue. We further establish the presence and function of olfactory transduction molecules in these cells using immunocytochemistry, calcium imaging and molecular methods. Western blot analysis revealed the expression of neurotransmitter receptors for dopamine (D2R), serotonin (5HT2C) and NMDA subtypes 1 and 2A/2B. Stimulation with dopamine or serotonin enhanced receptor G protein activation in a subtype specific manner, based on 35S-GTP incorporation assay. Functional characteristics of the cultured cells are demonstrated through enhanced tyrosine phosphorylation of NMDAR 2A/2B and recruitment of signaling partners in response to NMDA stimulation. The array of neuronal characteristics observed here establish that proliferating cells derived from the human olfactory epithelium differentiate in vitro to express functional and molecular attributes of mature olfactory neurons. These cultured neural cells exhibit neurotransmitter pathways important in a number of neuropsychiatric disorders. Their ready availability from living humans thus provides a *

Negative symptoms of schizophrenia correlate with impairment on the University of Pennsylvania Smell Identification Test

“…Several studies have suggested that the processing of olfactory information is involved in several brain regions, including right orbitofrontal cortex and amygdala, which also play a role in mediating emotional experience and expression (Davidson and Slagter, 2000; Francis et al, 1999; Gur et al, 1994; Moberg et al, 2003; Rolls, 1999; Zald and Pardo, 1997; Zatorre et al, 1992). In addition, recent evidence indicates that there are abnormalities in olfactory epithelium and olfactory receptor neurons in patients with SZ (Arnold et al, 2001; Arnold et al, 1998; Borgmann-Winter et al, 2009; Feron et al, 1999; McCurdy et al, 2006). …”

Oxidative stress and schizophrenia

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Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: Utility and limitation of the surrogate tissues in research for brain disorders

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