Lohi’s group compared the metabolite profiles of blood samples collected from 20 fearful and 21 non-fearful control dogs representing two breeds. The findings illustrated clear differences in many metabolites between the two canine groups.
Glutamine elevated in fearful dogs
The study exposed a significant link between fearfulness and an elevated glutamine level in the blood in both of the breeds studied, German Shepherds and Great Danes. Glutamine is one of the most important amino acids in the body, responsible for several duties in the brain, kidneys and the intestinal tract. It serves as a precursor for glutamate, a neurotransmitter identified in prior studies as having an important role in various mental disorders related to fear.
“The elevated glutamine concentration in fearful dogs is a fascinating discovery, with chronic stress stemming from fearfulness as a potential explanation. That can raise cortisol levels and, thus, also the glutamine concentration in blood. The importance and causalities of this change must be further investigated by using an even more extensive dataset,” explains Professor Hannes Lohi.
Breed-specific change in SDMA, a renal biomarker
The findings demonstrated that the age and gender of the dog, or any potential fasting before sampling, had no impact on the differences identified. Instead, the concentration of symmetric dimethylarginine (SDMA), a measure of renal function, varied greatly depending on the breed. SDMA is a diagnostic marker used to determine renal failure in clinical diagnostics. This is the first time it has been linked with canine behavioural disorders or similar disease conditions in other species.
“Dogs from two different breeds took part in our project, which prompted us to observe whether breed has any effect on the metabolite differences between fearful dogs and the control subjects. What we found was that fearful Great Danes had an elevated SDMA level, whereas no significant difference was seen between fearful and non-fearful German Shepherds. This elevation may also relate to the chronic stress experienced by fearful dogs,” says Jenni Puurunen, MSc, the principal author of the article and a doctoral student at the University of Helsinki.
The research carried out by Lohi’s group produced interesting findings from a rather limited, but very controlled dataset. Two weeks before the samples were collected, the participating dogs began having an identical diet. According to Lohi, much more extensive studies will be needed to substantiate the results and to determine clinically valid serum values related to fearfulness.
“Our ongoing research is aiming for larger datasets. In addition to fearfulness, we are investigating potential changes concerning other behavioural disorders. We have also been involved in developing new metabolomics test to enhance the analyses in future,” says Lohi.
The study was carried out in cooperation with the LC-MS Metabolomics Center at Biocenter Kuopio as part of a broader canine behavioural project conducted by the same research group, mapping out risk factors associated with canine behavioural problems and their connections with corresponding human diseases.
The research received support from a starting grant awarded by the European Research Council, as well as from ERA-NET NEURON, the University of Helsinki, the Academy of Finland, the Sigrid Jusélius Foundation, Biocenter Finland, the Jane and Aatos Erkko Foundation, the Orion-Farmos Research Foundation, the Finnish Kennel Club, the Canine Health Research Fund and the Folkhälsan Research Center.
Jenni Puurunen, Katriina Tiira, Katariina Vapalahti, Marko Lehtonen, Kati Hanhineva, Hannes Lohi. Fearful dogs have increased plasma glutamine and γ-glutamyl glutamine. Scientific Reports 2018 October 29. doi: 10.1038/s41598-018-34321-x