Behavioural and physiological responses of domestic dogs (Canis familiaris) to agonistic growls from conspecifics

Motivation-structural rule theory predicts that a sender producing harsh, low frequency sounds directed at a conspecific modifies the receiver's behaviour, in part, by communicating its willingness to escalate to an attack. Motivation-structural (MS) rules generally assume that receivers respond to this signal by retreating because of the threat encoded in the acoustic characteristics of the vocalisation. This assumption does not consider if alternative behavioural responses exist or how internal and environmental contexts affect receivers. This becomes an area for potential development of the MS theory when acknowledging that physiological and behavioural reactions may be related to distinct antithetical responses, such as Passive and Proactive coping strategies. To test if aggressive sound stimuli elicit consistent retreat responses by receivers, 42 dogs from shelters and private dog breeders were graded on behaviour and measures of salivary cortisol (a stress related steroid hormone) in response to an agonistic growl from an unknown, similarly sized conspecific. Results revealed that 52.4% (22/42) of dogs displayed retreat behaviours (Passive response), 33.3% (14/42) actively approached the growl source (Proactive response) and 14.3% (6/42) neither approached nor retreated (Neutral response). Post-test cortisol levels differed significantly between dogs in the Proactive, Passive and Neutral categories. Passively responding dogs averaged an 80% change in cortisol levels, Proactive dogs exhibited a 16.5% average cortisol change and Neutral responders displayed only a 6.4% change in cortisol. Although shelter dogs exhibited greater changes in cortisol, they did not differ significantly from the privately-owned dogs. This study verified that overt, observable behavioural responses reflect the physiological stress responses as measured by cortisol changes exhibited by domestic dogs. Results also suggested that experiences may influence how dogs to threatening stimuli from conspecifics respond-behaviourally and physiologically. A protocol providing a simulated threatening interaction with a dog, which does not bring the animals into direct contact, would have important implications for shelter staff in terms of how dog-dog introductions are managed, housing arrangements, potential training, matching dogs to owners and what advice shelter staff could offer to new owners. A corrigendum to this article was published in Applied animal behaviour science, 164, p. 92, doi:10.1016/j.applanim.2015.01.0018 page(s

Central Kynurenine Pathway Shift with age in Women

Age is considered a dominant risk factor in the development of most neurodegenerative disorders. The kynurenine pathway, a major metabolic pathway of tryptophan is altered in the majority of neurodegenerative disorders. In this study, we have analysed CSF samples from 49 healthy women across a wide age range (0–90) for kynurenine pathway metabolites and the inflammatory marker neopterin. Our results show central tryptophan metabolism is increased with age in women, with an apparent shift towards the neurotoxin quinolinic acid. We also observed an increase in central levels of the inflammatory marker neopterin with age and a positive correlation between neopterin and kynurenine pathway activation. We conclude that, the changes that occur in the kynurenine pathway as a result of normal ageing are mechanistically linked to increased inflammatory signalling and have some explanatory potential with regard to age‐associated degenerative diseases in the CNS. Management of health in ageing and (preventative) treatment would do well to look to the kynurenine pathway for potentially novel solutions

Social stress during adolescence in Wistar rats induces social anxiety in adulthood without affecting brain monoaminergic content and activity

Adolescence has been described as an important period to acquire social competences required for adult life. It has been suggested that early stress experiences could affect the development of the brain at different levels. These changes in the brain during adolescence may be related with the development of psychopathologies such as depression and social anxiety in adulthood. In the first experiment, we examined long-term effects of repeated social stress during adolescence on adult social approach–avoidance behavior. For that purpose, adolescent male Wistar rats were exposed twice at postnatal day (Pnd) 45 and Pnd48 to the resident–intruder paradigm followed by three times psychosocial threat with the same resident. Three weeks after the last psychosocial threat experience the animals were behaviorally tested in a social approach–avoidance test. Socially stressed animals spent less time in the interaction zone with an unfamiliar male adult rat. These data suggest that animals exposed to social stress during adolescence show a higher level of social anxiety in adulthood. In the second experiment, we investigated whether these long-term effects of social stress during adolescence on behavior draw a parallel with changes in brain monoamine content, biosynthesis and turnover. Using the same experimental design as in the first experiment, HPLC analysis of various brain regions showed that there were no differences in monoamine content, monoamine biosynthesis and monoamines activity in the prefrontal cortex, hippocampus, hypothalamus and striatum in adulthood. These results indicate that long-lasting changes in social behavior following social stress during adolescence are not accompanied by changes in brain monoamine content, biosynthesis and turnover.

Expression of the kynurenine pathway in human peripheral blood mononuclear cells : implications for inflammatory and neurodegenerative disease

The kynurenine pathway is a fundamental mechanism of immunosuppression and peripheral tolerance. It is increasingly recognized as playing a major role in the pathogenesis of a wide variety of inflammatory, neurodegenerative and malignant disorders. However, the temporal dynamics of kynurenine pathway activation and metabolite production in human immune cells is currently unknown. Here we report the novel use of flow cytometry, combined with ultra high-performance liquid chromatography and gas chromatography-mass spectrometry, to sensitively quantify the intracellular expression of three key kynurenine pathway enzymes and the main kynurenine pathway metabolites in a time-course study. This is the first study to show that up-regulation of indoleamine 2,3-dioxygenase (IDO-1), kynurenine 3-monoxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) is lacking in lymphocytes treated with interferon gamma. In contrast, peripheral monocytes showed a significant elevation of kynurenine pathway enzymes and metabolites when treated with interferon gamma. Expression of IDO-1, KMO and QPRT correlated significantly with activation of the kynurenine pathway (kynurenine:tryptophan ratio), quinolinic acid concentration and production of the monocyte derived, pro-inflammatory immune response marker: neopterin. Our results also describe an original and sensitive methodological approach to quantify kynurenine pathway enzyme expression in cells. This has revealed further insights into the potential role of these enzymes in disease processes.18 page(s

Quantification of Hand Motor Symptoms in Parkinson's Disease: A Proof-of-Principle Study Using Inertial and Force Sensors

This proof-of-principle study describes the methodology and explores and demonstrates the applicability of a system, existing of miniature inertial sensors on the hand and a separate force sensor, to objectively quantify hand motor symptoms in patients with Parkinson's disease (PD) in a clinical setting (off- and on-medication condition). Four PD patients were measured in off- and on- dopaminergic medication condition. Finger tapping, rapid hand opening/closing, hand pro/supination, tremor during rest, mental task and kinetic task, and wrist rigidity movements were measured with the system (called the PowerGlove). To demonstrate applicability, various outcome parameters of measured hand motor symptoms of the patients in off- vs. on-medication condition are presented. The methodology described and results presented show applicability of the PowerGlove in a clinical research setting, to objectively quantify hand bradykinesia, tremor and rigidity in PD patients, using a single system. The PowerGlove measured a difference in off- vs. on-medication condition in all tasks in the presented patients with most of its outcome parameters. Further study into the validity and reliability of the outcome parameters is required in a larger cohort of patients, to arrive at an optimal set of parameters that can assist in clinical evaluation and decision-makin

Simplified overview of the kynurenine pathway of tryptophan metabolism.

<p>The three main enzymes: indoleamine 2,3-dioxygenase (IDO-1), kynurenine 3-monooxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) are shown abbreviated in bold italics whilst the main metabolites measured in this study are written in bold.</p

Correlations of IDO-1, KMO and QPRT expression (gMFI) with KYN:TRP ratio, QUIN concentration (nM) and neopterin levels (nM).

<p>Data was log¹⁰ transformed to normalize distributions. Straight-line fits show least squares regression with the r² value providing a summary of fit. <i>P</i> values were computed using ANOVA for a regression analysis of the total variation for each correlation (n = 24).</p

Antibodies used in flow cytometry experiments.

<p>IDO-1: indoleamine 2,3-dioxygenase; KMO: kynurenine 3-monoxygenase; QPRT: quinolinate phosphoribosyltransferase; Ig: immunoglobulin; APC: allophycocyanin; FITC: fluorescein isothiocyanate.</p><p>Antibodies used in flow cytometry experiments.</p

Concentrations of KP metabolites in the supernatants of IFN-γ activated PBMCs.

<p>Levels of KP metabolites: tryptophan (TRP) and kynurenine (KYN)-shown as TRP:KYN ratio (<b>A</b>); 3-hydroxykynurenine (3-HK) (<b>B</b>); 3-hydroxyanthranillic acid (3-HAA) (<b>C</b>); anthranilic acid (AA) (<b>D</b>); quinolinic acid (QUIN) (<b>E</b>); picolinic acid (PIC) (<b>F</b>) and the pro-inflammatory marker: neopterin (<b>G</b>) were measured by UHPLC or GC-MS (QUIN and PIC only) in the supernatants of PBMCs untreated (control-black bars) or treated with IFN-γ (500 IU/mL-grey bars) at 24, 48 and 72 hours of culture. Values represent the mean±SEM of 4 independent biological repeats (ns = no significant difference, *<i>p</i><0.05, **<i>p</i><0.01, **<i>p</i><0.001).</p