Fearful dogs have increased plasma glutamine and γ-glutamyl glutamine

Abstract

Anxiety-related disorders, including fearfulness are common and leading welfare problems among the worldwide dog population. The etiology of anxieties is complex and affected by genetic and environmental factors. Thus, there is a need for more comprehensive approaches, such as metabolomics, to understand the causes of anxiety and to identify anxiety-related biomarkers for more efficient diagnostic and treatment options. To study metabolic alterations related to canine fearfulness, a non-targeted plasma metabolite profiling was performed in a cohort of 20 fearful and 21 non-fearful dogs. The results showed that nine metabolic features were significantly associated with fearfulness. The most prominent change included increased plasma glutamine and γ-glutamyl glutamine (γ-Glu Gln) in fearful dogs across breeds. Alterations in glutamine metabolism have previously been associated with several psychiatric disorders, indicating the relevance of this finding also in dogs. In addition, we describe a novel breed-specific association between renal biomarker symmetric dimethylarginine (SDMA) and canine fearfulness. These observed metabolic alterations may result from high levels of prolonged psychological stress in fearful dogs.

Active and social life is associated with lower non-social fearfulness in pet dogs

“…Thus, more research is needed to investigate what amount of exercise is beneficial for protecting dogs against non-social fear. Recent studies have also revealed increased levels of stress-related biomarkers in fearful dogs 38,39 . On the other hand, earlier studies have shown that fearful dogs have difficulty in solving cognitive tasks and show more stress-related behaviour when solving the puzzle 57,58 , suggesting that fearful dogs are not ideal partners for training.…”

A novel genomic region on chromosome 11 associated with fearfulness in dogs

“…We recently reported novel loci for canine fearfulness and noise sensitivity 14 . In addition, we have previously reported changes such as increased plasma glutamine levels in fearful dogs 16,17 . Candidate loci and genes have also been reported for example for canine fear and aggression 18 , social behaviour 19,20 , and obsessivecompulsive disorder 21,22 .…”

Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

“…These studies point to the role of oxidative stress, alterations in AA and energy metabolism (i.e., mitochondrial regulation) and neurotransmission [35,36]. Glutamine, γ-glutamyl-glutamine Glutamine metabolism [38] Recently, metabolomics approaches were also conducted on fearful dogs (Table 2). Compared to classical rodent models, dogs share comparable lifestyle and environmental factors like humans and are even genetically and physiologically closer to humans [38].…”

“…Glutamine, γ-glutamyl-glutamine Glutamine metabolism [38] Recently, metabolomics approaches were also conducted on fearful dogs (Table 2). Compared to classical rodent models, dogs share comparable lifestyle and environmental factors like humans and are even genetically and physiologically closer to humans [38]. The study revealed changes in glutamine metabolism (i.e., higher plasma glutamine and γ-glutamyl-glutamine levels in fearful vs. non-fearful dogs).…”

“…Thus, sufficient function of the glutamate-glutamine cycle is of utmost importance for appropriate glutaminergic neurotransmission [43]. As glutamate plays an important role in fear conditioning [44,45], dysfunction of this cycle has been suggested to be involved in different forms of anxieties, thus playing a central role in a wide spectrum of neuropsychiatric disorders, such as schizophrenia, depression and post-traumatic stress disorder [38]. Indeed, as summarized in Tables 1-4, disturbances in glutamate concentration is a common finding in animal studies of different psychiatric disorders.…”