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

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.

Transcriptional network analysis in frontal cortex in Lewy body diseases with focus on dementia with Lewy bodies

“…Expression of taste and olfactory receptors and down‐stream obliged functional signaling pathways in the CNS and their deregulation in neurodegenerative diseases is intriguing. It is possible that these receptors in brain are not involved in the perception of odors and taste but rather correspond to new central chemoreceptors looking for putative ligands or interacting complementary receptors . TASRs are significantly upregulated in frontal cortex in PD and DLB , and our findings further indicate that deregulation of TASRs in frontal cortex occurs in iLBD as well.…”

Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety‐like behavior

“…We found that a specific vomeronasal receptor gene (Vmn1r232) is overexpressed in dominant animals, whereas 3 olfactory receptor genes out of 5 presented higher expression in subordinates. Although olfactory receptors have been widely located outside olfactory regions (46,47), vomeronasal receptors have not been explored so far. To our knowledge, this is the first description of vomeronasal receptors in the mPFC of male mice, reinforcing our hypothesis of their use as potential biomarkers of social dominance.…”

“…We found 21 olfactory and 9 vomeronasal receptors differentially expressed between both social statuses in the mPFC. Olfactory receptor expression outside the olfactory system has been described (46,47). However, no previous studies have reported expression of vomeronasal receptor genes in the CNS to our knowledge.…”

Regulatory role of G9a and LSD1 in the Transcription of Olfactory Receptors during Leukaemia Cell Differentiation

“…Moreover, ORs are also expressed in germinal cells, embryos, and developing heart and muscle, suggesting that they function during developmental stages474849505152. ORs in non-olfactory tissues do not appear to be related to olfaction activity but rather perform their own different tissue-dependent functions53.…”