CB1-5-HT2A heteromers in schizophrenia patients: Human studies in pro-neurons of the olfactory epithelium

Introduction Despite multiple clinical and preclinical studies investigating schizophrenia, the neurobiological basis of this disease is still unknown. The dysregulation of the serotonergic system, in particular the 5-HT2A receptor and the endocannabinoid system have been postulated as possible causes of schizophrenia. Objectives The aim of this study is to evaluate the expression of CB1-5-HT2A receptor heteromers in primary cultures of pro-neurons from the olfactory epithelium in schizophrenia patients and control subjects. Methods We recruited a group of 10 healthy volunteers and 10 patients diagnosed with schizophrenia, who were treated with atypical antipsychotics, were clinically stable and had an illness duration range from 1 up to 15 years. The patients were diagnosed with schizophrenia from the medical record and confirmed by the structured clinical interview for DSM disorders. The expression of CB1-5-HT2A receptor heteromers in primary cultures of pro-neurons from the olfactory epithelium was quantified using proximity ligation assays and confocal microscopy. Results Olfactory epithelium pro-neurons were viable and expressed the neuronal marker, III-β tubulin. We also established the presence and the functionality of CB1-5-HT2A receptor heteromers in these cells using the proximity ligation and cAMP activity assays, respectively. Heteromer expression was significantly increased in schizophrenia patients with respect to controls. Conclusions This highly innovative methodology will allow the noninvasive, low-cost study of new biomarkers for schizophrenia in a model closely related to the central nervous system.