Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.

Isidro Ferrer,Stefano Gustincich,Paula Garcia-Esparcia,Eleonora Aronica,Margarita Carmona,Gabor G Kovacs,Alice Grison,Eva Carro

doi:10.3389/fnagi.2016.00163

Abstract

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells’ own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.

Highlights

Chemical signals acting on appropriate receptors are the most common and precise form of communication
These observations indicate that: (i) cortical olfactory receptors (ORs) and taste receptors (TASR) are vulnerable to PARKINSON’S DISEASE (PD); (ii) deregulation of selective OR and TASR genes occurs at relative early stages of the disease; (iii) altered OR and TASR gene expression is not dependent on treatment because changes are observed in incidental cases discovered on post-mortem neuropathological examination in individuals who did not receive drug therapy; (iv) OR gene down-regulation predominates but the expression of some OR genes is preserved, and only a few of them are up-regulated; (v) deregulation of TASR genes at the same stages of the disease and in the same region is more variable; and (vi) deregulation of certain ORs and TASRs in PD is genderdependent
Parallel studies of TASR mRNA expression reveal no significant differences in the expression of analyzed genes in Alzheimer’s disease (AD), up-regulation of six of the six analyzed genes in PROGRESSIVE SUPRANUCLEAR PALSY (PSP), predominant up-regulation in SPORADIC CREUTZFELDT-JAKOB DISEASE (sCJD), and increased or depressed mRNA expression of TASR genes depending on gender in PD (Table 1)

Summary

ORs in CNS

Preliminary parallel observations have shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain

INTRODUCTION

PSP sCJD

Findings

FINAL COMMENTS