A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of ...

Measuring Active and Passive Tameness Separately in Mice

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two ...

Ibaraki University

Obihiro University of Agriculture and Veterinary Medicine

To improve the quality of life of animals, understanding of stress-induced changes is necessary. Previously, we established a subchronic and mild social defeat stress (sCSDS) model in mice, which showed significantly higher body weight gain, food intake, and water intake compared to control mice. In this study, we elucidated metabolic profiles of plasma, liver, and urine in sCSDS mice by using metabolome and biochemical analyses. There was no significant difference between defeated and control mice in the plasma metabolites. In the liver of sCSDS mice, levels of taurocyamine (GES), phosphorylcholine, D-alanyl-D-alanine (D-ala-D-ala), and 1-methylnicotinamide (MNA) were elevated compared to controls. Taurine plays a role in osmotic regulation, and GES is a potential inhibitor of the taurine transporter. The polydipsia and increased body water content in sCSDS mice may disrupt body fluid balance following GES elevation. Furthermore, sCSDS increased heart and spleen weight significantly. Because MNA and D-ala-D-ala have anti-inflammatory and hepatoprotective effects, they may reduce inflammation in the liver of sCSDS mice. Finally, suppressed excretion of urine sodium was observed in sCSDS mice. Therefore, sCSDS induces various changes in metabolite concentrations, especially related to osmoregulation and inflammation, that may be used as biomarkers for stress-induced changes in animals.

Plasma and liver metabolic profiles in mice subjected to subchronic and mild social defeat stress.

Effects of chronic taurine administration on gene expression, protein translation and phosphorylation in the rat hippocampus.

Objectives The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. Methods Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. Results Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P < 0.05). For comparison, the susceptible-like phenotype rates were estimated at 12.5 and 8.3% in healthy control mice fed semi-purified and non-purified diets, respectively. Discussion These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

We developed a novel method to evaluate the nest-building behavior of mice using an inexpensive depth camera. The depth camera clearly captured nest-building behavior. Using three-dimensional information from the depth camera, we obtained objective features for assessing nest-building behavior, including "volume," "radius," and "mean height". The "volume" represents the change in volume of the nesting material, a pressed cotton square that a mouse shreds and untangles in order to build its nest. During the nest-building process, the total volume of cotton fragments is increased. The "radius" refers to the radius of the circle enclosing the fragments of cotton. It describes the extent of nesting material dispersion. The "radius" averaged approximately 60mm when a nest was built. The "mean height" represents the change in the mean height of objects. If the nest walls were high, the "mean height" was also high. These features provided us with useful information for assessment of nest-building behavior, similar to conventional methods for the assessment of nest building. However, using the novel method, we found that JF1 mice built nests with higher walls than B6 mice, and B6 mice built nests faster than JF1 mice. Thus, our novel method can evaluate the differences in nest-building behavior that cannot be detected or quantified by conventional methods. In future studies, we will evaluate nest-building behaviors of genetically modified, as well as several inbred, strains of mice, with several nesting materials.

Assessing nest-building behavior of mice using a 3D depth camera.

Nest building is one of the innate behaviors that are widely observed throughout the animal kingdom. Previous studies have reported specific brain regions and genetic loci associated with nest building in mice. These studies mainly evaluated the nest structure, without observing the nesting process. In this study, we evaluated the effects of strain and learning on the nesting process of mice using a 3D depth camera. To determine the quality of the nest structure, a conventional scoring method, Deacon scores 1-5, was applied to the recorded depth images. The final score of the nest, latency to start nesting behavior, and latencies to reach Deacon scores 3-5, were determined using three genetically different mouse strains-C57BL/6NCrl (B6), DBA/2NCrlCrlj (DBA), and B6D2F1/Crl (B6D2F1). The final score of the DBA nest was significantly lower than that of the B6D2F1 nest, and DBA mice showed significantly longer latency to start nest building than the other two strains in the first trial. By observing the time course of nest building, we confirmed that DBA mice took significantly longer to build their nests than B6 and B6D2F1 mice. Although we did not find any significant differences between DBA and B6 mice in the final assessment of the nest based on the Deacon method, overnight monitoring of the nesting behavior using a 3D depth camera could elucidate the clear differences in the amount of time spent nesting between DBA and B6 mice. In addition, the learning effect was more evident in DBA mice than it was in B6 in terms of latencies to reach Deacon score 3-5 in five repeated trials. DBA mice showed a gradual decrease in latency to build, whereas nesting behaviors of B6 mice were relatively consistent throughout the five trials. Therefore, our 3D depth image method gives higher resolution and structural information regarding the nesting process in mice. Future genetic analyses using the 3D assessment system will provide novel insights into the complex genetic basis for nesting and other behaviors in animals.

Strain differences in temporal changes of nesting behaviors in C57BL/6N, DBA/2N, and their F1 hybrid mice assessed by a three-dimensional monitoring system.

Behavioral and physiological evaluations of animal models of depression are essential to thoroughly understand the mechanisms of depression in humans. Various models have been developed and characterized, and the socially defeated mouse has been widely used for studying depression. Here, we developed and characterized a mouse model of social aversion using a subchronic and mild social defeat stress (sCSDS) paradigm. Compared to control mice, sCSDS mice showed significantly increased body weight gain, water intake, and social aversion to dominant mice on the social interaction test. We observed nest building behavior in sCSDS mice using the pressed cotton as a nest material. Although sCSDS mice eventually successfully built nests, the onset of nest building was severely delayed compared to control mice. The underlying mechanism of this significant delay in nest building by sCSDS mice is unclear. However, our results demonstrate that nest building evaluation is a simple and useful assay for understanding behavior in socially defeated mice and screening drugs such as antidepressants.

Subchronic and mild social defeat stress alter mouse nest building behavior.

Dilute suspensions of charged colloidal particles with a short-range attraction and long-range repulsion can exhibit a variety of arrested states. In many applications using suspensions of charged nanoparticles, the optimization of the process requires the understanding of the mechanism underlying the stability and the rheological properties of the suspensions. In an attempt to clarify the solidification mechanism for dilute suspensions of tin dioxide (SnO2) nanoparticles, we present dynamic viscoelasticity, dynamic and static light scattering, and small-angle X-ray scattering experiments on a SnO2 nanoparticle suspension with a nanoparticle concentration of 25.0 wt % (volume fraction φ = 0.045). The behaviors of the observed dynamic and static structure factors reveal that the aging of SnO2 nanoparticles is Wigner glassy rather than gel-like.

Tatsuhiko Goto

College of Agriculture,
Cooperation between Agriculture and Medical Science

Ibaraki University

A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

Measuring Active and Passive Tameness Separately in Mice

Tatsuhiko Goto

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Ibaraki University

A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

Measuring Active and Passive Tameness Separately in Mice

College of Agriculture,
Cooperation between Agriculture and Medical Science