Neuroscience. 2016 Apr 21;320:160-71. doi: 10.1016/j.neuroscience.2016.01.057.

“Tasting” the cerebrospinal fluid: another function of the choroid plexus?

Joana Tomás*, Cecília Santos*, Telma Quintela*, Isabel Gonçalves*

*CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal

 

Abstract

The choroid plexus (CP) located in the brain ventricles, by forming the interface between the blood and the cerebrospinal fluid (CSF) are in a privileged position to monitor their composition. Yet, the mechanisms involved in this surveillance system remain to be identified. The taste transduction pathway senses some types of molecules, thereby evaluating the chemical content of fluids, not only in the oral cavity but also in other tissues throughout the body, such as some cell types of the airways, the gastrointestinal tract, testis and skin. Therefore, we hypothesized that the taste transduction pathway could be also operating in the CP to assess the composition of the CSF. We found transcripts for some taste receptors (Tas1R1, Tas1R2, Tas1R3, Tas2R109 and Tas2R144) and for downstream signaling molecules (α-Gustducin, Plcβ2, ItpR3 and TrpM5) that encode this pathway, and confirmed the expression of the corresponding proteins in Wistar rat CP explants and in the CP epithelial cells (CPEC). The functionality of the T2R receptor expressed in CP cells was assessed by calcium imaging, of CPEC stimulated with the bitter compound D-Salicin, which elicited a rise in the intracellular Ca2+. This effect was diminished in the presence of the bitter receptor blocker Probenecid. In summary, we described the expression of the taste-related components involved in the transduction signaling cascade in CP. Taken together, our results suggest that the taste transduction pathway in CPEC makes use of T2R receptors in the chemical surveillance of the CSF composition, in particular to sense bitter noxious compounds.

Keywords: Choroid Plexus; Taste transduction pathway; Bitter taste receptor; Blood-CSF barrier.

 

Supplement 

The choroid plexus (CP), the main site of cerebrospinal fluid (CSF) production, are highly vascularized branched structures that protrude into each ventricle of the brain. The CSF fills the brain ventricles, the cisternal and subarachnoid space, covers the spinal cord and, therefore is in close contact with brain parenchyma. CPs constitute the blood-CSF barrier and synthesize and secrete a wide range of compounds determining their bioavailability in the central nervous system (CNS). Blood and brain-born molecules, in both sides of the barrier, can alter the CP secretome and modulate CSF composition accordingly. Moreover, the CP monitors the CSF for the presence of noxious compounds and protects the brain against neurotoxic insults by using a complex detoxification system of the CSF suggesting the existence of mechanisms to assess their composition (1, 2).

The mammalian gustatory system, firstly described in the oral cavity, recognizes five basic taste qualities: salty, sour, sweet, umami and bitter, which enable the assessment of nutritional value of food constituents and prevent the ingestion of toxic substances. The molecular mediators of sweet, umami and bitter have been identified as members of the  G protein-coupled receptors (GPCRs) family and are referred as taste receptor type1 (T1R) and taste receptor type2 (T2R). The T1R family has 3 members, that form sweet and umami receptors, whereas the T2R family consists of 25 GPCRs that mediate bitter taste (3).

The GPCRs are cell transmembrane proteins, representing the largest receptor family in the mammalian genome, known to bind an array of sensory inputs and compounds, including: carbohydrates, proteins and peptides, amines, ions, volatile compounds and photons. The binding of a ligand to the GPCR provokes its activation, converting extracellular stimuli into intracellular signals, mediating cellular and physiological responses including the taste and smell. There are several human diseases linked to mutations in GPCRs, and it is important to note that 40% of the drugs on the market target GPCRs.

Accumulating molecular evidence indicates that the taste receptors are widely expressed beyond the oral cavity, throughout the body, with functional roles including regulation of gut motility, maintenance of the glomerulus and renal tube structure, protective airway reflexes, between others (4).

 

 

FIG1

Fi.1- The key components of the taste chemosensory apparatus are present and are functional in murine choroid plexus. D-salicin seem to trigger the taste signaling pathway (the responses of CP cells to bitter compounds were evaluated, in vitro, by changes in intracellular Ca2+). Taste-like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the cerebrospinal fluid (CSF) composition, and to elicit responses to modulate and maintain brain homeostasis.

 

Within the frame of a previous study about the effect of hormonal background in the CP transcriptome, we found that taste receptors are expressed in CP (5). So, we hypothesized that the taste-like chemosensory machinery may be used by the CP, enabling an accurate detection of the CSF composition, thereby inducing cellular responses according to the central nervous system state. In the present study, using an in vitro rat CP model, we found the presence and the functionality of taste receptors of family 1 and 2 (T1Rs and T2Rs) and the signalling pathway effector molecules. To the best of our knowledge, this is the first such study describing the activity of taste transduction pathway in this brain structure: The Choroid Plexus.

 

The importance of this study:

  1. The study shows that the taste transduction machinery is present in the CP, responding to a bitter compound, via bitter taste receptors.
  2. It is likely that the taste pathway may be one of the mechanisms of cerebrospinal fluid chemical composition surveillance of the CP.

 

References:

(1) Strazielle N, Ghersi-Egea JF (2000) Choroid plexus in the central nervous system: biology and physiopathology. Journal of neuropathology and experimental neurology 59:561-574.

(2) Emerich DF; Skinner SJ; Borlongan CV; Vasconcellos AV, Thanos CG (2005) The choroid plexus in the rise, fall and repair of the brain. Bioessays 27:262-274.

(3) Chandrashekar J; Hoon MA; Ryba NJ, Zuker CS (2006) The receptors and cells for mammalian taste. Nature 444:288-294.

(4) Foster SR; Roura E, Thomas WG (2014) Extrasensory perception: odorant and taste receptors beyond the nose and mouth. Pharmacology & therapeutics 142:41-61.

(5) Quintela T; Goncalves I; Carreto LC; Santos MA; Marcelino H; Patriarca FM, Santos CR (2013). Analysis of the effects of sex hormone background on the rat choroid plexus transcriptome by cDNA microarrays. PLoS One, Apr 9;8(4):e60199.

 

Acknowledgements: This work is supported by FEDER funds through the POCI – COMPETE 2020 – Operational Programme Competitiveness and Internationalisation in Axis I – Strengthening research, technological development and innovation (Project No. 007491) and National Funds by FCT – Foundation for Science and Technology (Project UID/Multi /00709)

 

Contact:

Isabel Theriaga Gonçalves

Health Sciences Research Centre: CICS-UBI, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal

E-mail: igoncalves@fcsaude.ubi.pt

 

 

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