‘Smelling’ the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus

Abstract

The olfactory-type signaling machinery has been known to be involved not only in odorant detection but also in other tissues with unsuspected sensory roles. As a barrier, the choroid plexus (CP) is an active participant in the monitoring of the cerebrospinal fluid (CSF), promptly responding to alterations in its composition. We hypothesized that olfactory signaling could be active in CP, contributing to the surveillance of the CSF composition. We determined the mRNA and protein expression of the major components of the olfactory transduction pathway in the rat CP, including odorant receptors, the olfactory G-protein (Gaolf), adenylate cyclase 3 and cyclic nucleotide-gated channel 2. The functionality of the transduction pathway and the intracellular mechanisms involved were analyzed by DC field potential recording electrophysiological analysis, in an ex vivo CP-brain setup, using polyamines as stimuli and blockers of the downstream signaling pathways. Concentration-dependent responses were obtained for the polyamines studied (cadaverine, putrescine, spermine and spermidine), all known to be present in the CSF. Transfection of a CP epithelial cell line with siRNA against Gaolf effectively knocked down protein expression and reduced the CP cells' response to spermine. Thus, the key components of the olfactory chemosensory apparatus are present and are functional in murine CP, and polyamines seem to trigger both the cAMP and the phospholipase C-inositol 1,4,5-trisphosphate pathways. Olfactory-like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the CSF composition, and to elicit responses to modulate and maintain brain homeostasis.

Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors

“…In this context, OR2L13 is not only expressed in brain, it is also dysregulated in Parkinson’s disease (Garcia-Esparcia et al, 2013). The physiological function of ORs in the nervous system is far from understood, but according to the hypothesis by Otaki and Goncalves, ORs might play a role either in the detection of alterations in the chemical composition of cerebrospinal fluid, and therefore, the regulation of brain homeostasis or in developmental processes such as axon guidance and target recognition (Otaki et al, 2004; Goncalves et al, 2016). …”

“…They are also of major importance for the regulation of apoptosis, cytokinesis, hormone secretion and differentiation (Braun et al, 2007; Zhang et al, 2012; Maßberg et al, 2015; Gelis et al, 2016; Manteniotis et al, 2016a,b; Massberg et al, 2016; Tsai et al, 2016). However, the expression and localization of ORs in different areas of the brain, the spinal cord, the trigeminal (TG) and dorsal root ganglia (DRG) were recently described (Otaki et al, 2004; Garcia-Esparcia et al, 2013; Flegel et al, 2015; Goncalves et al, 2016). Yet, the physiological function of ORs in the nervous system remains elusive.…”

[P1–214]: ANALYSIS OF THE EXPRESSION OF TASTE AND OLFACTORY RECEPTORS IN CHOROID PLEXUS AND ORBITOFRONTAL CORTEX OF ALZHEIMER's DISEASE PATIENTS

“…ORs and olfactory signalling pathway components were also found to be expressed and to be functional in murine CP, suggesting that they might be involved in the CP chemical surveillance apparatus in detecting alterations in the CSF composition and eliciting responses that modulate and maintain brain homeostasis (Gonçalves et al, 2016).…”

“…ORs have been also identified in several areas of the brain such as the cerebral cortex in mice (Kang & Koo, 2012) and the murine choroid plexus (Gonçalves et al, 2016). The presence of…”

The choroid plexus: Simple structure, complex functions

“…The components of the olfactory, taste, and vomeronasal signaling pathways identified in the CP might be essential components of brain chemical surveillance machinery to keep up with brain homeostasis. In particular, the CP senses bitter noxious compounds (Tomás, Santos, Quintela, & Gonçalves, ), via taste receptors (Tomás et al, ) and perceive the presence of polyamines via odorant‐related receptors (Gonçalves et al, ).…”