A comparison of methods to measure central and peripheral oxytocin concentrations in human and non-human primates

Manon Dirheimer,Carmine Mottolese,Raphaëlle Mottolese,Arthur Lefevre,Jean-René Duhamel,Angela Sirigu

doi:10.1038/s41598-017-17674-7

Manon Dirheimer, Carmine Mottolese + Show 4 more

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https://doi.org/10.1038/s41598-017-17674-7

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Abstract

Oxytocin (OT) concentration in the blood is considered to be a marker of its action in the brain. However, two problems have emerged when measuring OT level in the blood. First, it is unclear whether different methods of assessment lead to similar OT values. Second, it is unclear if plasma OT concentrations is informative on what OT does in the brain. To clarify these issues, we collected cerebrospinal fluid (CSF) from the brain ventricle of 25 patients during surgery to compare with plasma OT after simultaneous blood withdrawal. Additionally, we collected 12 CSF and blood samples from non-human primates while awake or under anaesthesia. We used four methods to assay OT concentrations: Commercial EIA with/without extraction, laboratory developed EIA with filtration and RIA with extraction. Three of these methods showed a positive correlation between plasma and CSF OT, suggesting a link between plasma and central OT, at least under specific testing conditions. However, none of the methods correlated to each other. Our results show major disagreements among methods used here to measure peripheral and brain OT and therefore they call for more caution when plasma OT is taken as a marker of central OT.

Highlights

Oxytocin (OT) is a neuropeptide synthesized in the hypothalamus which has a wide range of actions both in the brain and in the body[1]
The paraventricular (PVN) and the supraoptic (SON) nuclei of the hypothalamus, the centres of OT synthesis, contain magnocellular neurons with axons projecting to the posterior pituitary, where OT is released into the bloodstream[5]
We found a significant relationship between OTp and OTc with three methods (OT ELS, OT Lg and OT M) but the one measure considered to be the gold standard for OT measurement (OT RIA) did not led to similar results. These findings call for more caution when considering what information is inferred from peripheral OT levels

Summary

Introduction

Oxytocin (OT) is a neuropeptide synthesized in the hypothalamus which has a wide range of actions both in the brain and in the body[1]. These results were confirmed recently by studies showing central projections of OT neurons, notably an axonal magnocellular pathway in the forebrain[12,13,14]. Following these results, it is reasonable to conclude that, under certain conditions, there is a coordinated axonal release of OT in specific brain areas and in the blood. Two studies performed in headache patients and in children have found a correlation between OTp and OTc15,16 four others failed to find a significant link[17,18,19,20] In all of these experiments, CSF OT was collected by doing a lumbar puncture, a method that extracts CSF in a region far from OT synthesis site.

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