Abstract
The choroid plexus (CP) constitutes a barrier between the blood and the cerebrospinal fluid (CSF) which regulates the exchange of substances between these two fluids through mechanisms that are not completely understood. Polyamines as spermine, spermidine and putrescine are produced by all cells and are present in the CSF. Interestingly, their levels are altered in some neuronal disorders as Alzheimer’s and Parkinson’s diseases, thus increasing the interest in their signalling in the central nervous system (CNS). Cadaverine, on the other hand, is synthetized by the intestinal microbiome, suggesting that the presence of this bacterial metabolite in the CSF requires that it is up taken to the CNS across brain barriers. We knew that polyamines are detected by the olfactory signalling cascade operating at the CP, but the receptor involved had not been identified. The zebrafish TAAR13c was the only receptor known to bind a polyamine-cadaverine. Thus, we searched for a human receptor with homology to TAAR13c and found that some human TAARs including TAAR1 showed great homology. Then, we confirmed the expression of TAAR1 mRNA and protein in a human cell line of the CP, and in human CP samples. Calcium imaging assays after TAAR1 knockdown in these cells with a specific siRNA against TAAR1 showed a consistent reduction in the responses of these cells to cadaverine and spermidine, but not to spermine, suggesting that TAAR1 is activated by cadaverine and spermidine, but not spermine.
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Abbreviations
- CP:
-
Choroid plexus
- CSF:
-
Cerebrospinal fluid
- TAAR:
-
Trace amine-associated receptor
- PA:
-
Polyamines
- CNS:
-
Central nervous system
- CPEC:
-
Choroid plexus epithelial cells
- BCSFB:
-
Blood-CSF barrier
- AJs:
-
Adherents junctions
- zb:
-
Zebrafish
- GEO:
-
Gene expression omnibus
- HIBCPP:
-
Human epithelial CP papilloma cells
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Funding
This work was partially supported by “Programa Operacional do Centro, Centro 2020” through the funding of the ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01-0145-FEDER-000013). This work is supported by funds from the Health Sciences Research Centre (CICS-UBI) through National Funds by FCT – Portuguese Foundation for Science and Technology (UID / Multi / 00709/2019). Almeida-Santos, D. and Duarte, A.C. are recipients of a MSc fellowship supported by the ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01-0145-FEDER-000013). The authors would like to thank to A. Borges for their support in microscopy experiments and to the PPBI-Portuguese Platform of BioImaging (POCI-01-0145-FEDER-022122).
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Almeida-Santos, D., Duarte, A.C., Gonçalves, I. et al. Cadaverine and Spermine Elicit Ca2+ Uptake in Human CP Cells via a Trace Amine-Associated Receptor 1 Dependent Pathway. J Mol Neurosci 71, 625–637 (2021). https://doi.org/10.1007/s12031-020-01684-8
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DOI: https://doi.org/10.1007/s12031-020-01684-8