Cre-Activation in ErbB4-Positive Neurons of Floxed /NMDA Receptor Mice Is Not Associated With Major Behavioral Impairment.

Extensive evidence suggests a dysfunction of the glutamate NMDA receptor (NMDAR) in schizophrenia, a severe psychiatric disorder with putative early neurodevelopmental origins, but clinical onset mainly during late adolescence. On the other hand, pharmacological models using NMDAR antagonists and the clinical manifestation of anti-NMDAR encephalitis indicate that NMDAR blockade/hypofunction can trigger psychosis also at adult stages, without any early developmental dysfunction. Previous genetic models of NMDAR hypofunction restricted to parvalbumin-positive interneurons indicate the necessity of an early postnatal impairment to trigger schizophrenia-like abnormalities, whereas the cellular substrates of NMDAR-mediated psychosis at adolescent/adult stages are unknown.

Evaluation of Potential Sustainable Bedding Substrates Focusing on Preference, Behavior, and Stress Physiology in Rats-A Pilot Study.

Ensuring optimal housing conditions for laboratory animals is a crucial prerequisite for high-quality and ethically justifiable in vivo science. In addition to guaranteeing animal welfare and promoting scientific validity, environmental sustainability is also increasingly gaining attention in laboratory animal facilities. Consequently, comprehensive management of such aspects is one of the core tasks of any research vivarium.

Systematic analysis of severity in a widely used cognitive depression model for mice.

Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human condition. Modern bioethics requires balancing scientific progress with animal welfare concerns.

Effects of Soy in Laboratory Rodent Diets on the Basal, Affective, and Cognitive Behavior of C57BL/6 Mice.

Soy is one of the most common sources of protein in many commercial formulas for laboratory rodent diets. Soy contains isoflavones, which are estrogenic. Therefore, soy-containing animal diets might influence estrogen-regulated systems, including basal behavioral domains, as well as affective behavior and cognition.

Effect of three different forms of handling on the variation of aggression-associated parameters in individually and group-housed male C57BL/6NCrl mice.

Mice are social animals hence group-housing of mice is preferred over individual housing. However, aggression in group-housed male mice under laboratory housing conditions is a well-known problem leading to serious health issues, including injury or death. Therefore, group-housed mice are frequently separated for welfare reasons.

Marble burying as compulsive behaviors in male and female mice.

Marble burying is considered an, albeit controversial, animal model of the compulsive like behaviors of obsessive-compulsive disorder (OCD). Hallmark features of OCD patients are similarities and, more prominent, differences from anxiety disorders, e.g.

May the use of different background strains 'strain' the stress-related phenotype of GR mice?

Genetically altered mice are available on different background strains. While respective backcrosses are often performed for pragmatic reasons, e.g.

Effects of Embryo Transfer on Emotional Behaviors in C57BL/6 Mice.

Microbiologic standardization plays a key role in the management of animal facilities because contamination of stock could affect the health status and wellbeing of animals and thereby induce artifacts in biomedical research. One common method to avoid the dissemination of pathogens is embryo transfer (ET). Although disturbances in the perinatal environment may cause long-lasting effects on the behavior and physiology of mouse offspring, the influences of ET during this sensitive phase have not yet been addressed.

Mice age - Does the age of the mother predict offspring behaviour?

Increasing paternal age is known to be associated with a great variety of psychiatric disorders such as schizophrenia or autism. Hence the factor "age" may be taken as strategic tool to analyse specific scientific hypotheses. Additionally, this finding also needs to be addressed in rather pragmatically performed breeding protocols of model organisms, since otherwise artefacts may challenge the validity of the results.

Bred to breed?! Implications of continuous mating on the emotional status of mouse offspring.

Working with mice represents a smart method to study pathophysiological mechanisms in vivo. However, using animals as model organisms also bears immense caveats. While many aspects in animal research are meanwhile standardized (e.

What makes a good mother? Implication of inter-, and intrastrain strain "cross fostering" for emotional changes in mouse offspring.

Currently, the mouse represents the preferred model organism among mammals used for animal studies. Due to a great availability of mutant strains it represents a standard method to analyze in vivo the effects of targeted gene manipulations. While this - at least in theory - represents a valuable tool to elucidate the pathophysiology of certain human diseases, there are several caveats which need to be considered working with animals.

Differences in mouse maternal care behavior - is there a genetic impact of the glucocorticoid receptor?

Depressive episodes are frequently preceded by stressful life events. Evidence from genetic association studies suggests a role for the glucocorticoid receptor (GR), an essential element in the regulation of stress responses, in the pathophysiology of the disorder. Since the stress response system is affected by pregnancy and postpartum-associated changes, it has also been implicated in the pathophysiology of postpartum depression.

Effect of population heterogenization on the reproducibility of mouse behavior: a multi-laboratory study.

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions.

Altering BDNF expression by genetics and/or environment: impact for emotional and depression-like behaviour in laboratory mice.

According to the "neurotrophin hypothesis", brain-derived neurotrophic factor (BDNF) is an important candidate gene in depression. Moreover, environmental stress is known to represent a risk factor in the pathophysiology and treatment of this disease. To elucidate, whether changes of BDNF availability signify cause or consequence of depressive-like alterations, it is essential to look for endophenotypes under distinct genetic conditions (e.

The suitability of 129SvEv mice for studying depressive-like behaviour: both males and females develop learned helplessness.

Behavioural studies using transgenic techniques in mice usually require extensive backcrossing to a defined background strain, e.g. to C57BL/6.

Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice.

The 5-HT(4) receptor is a new potential target for antidepressant treatment and may be implicated in the pathogenesis of depression. This study investigated differences in 5-HT(4) receptor and 5-HT transporter (5-HTT) binding by quantitative autoradiography of [(3)H]SB207145 and (S)-[N-methyl-(3)H]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control.

Reduced hippocampal neurogenesis in the GR(+/-) genetic mouse model of depression.

Glucocorticoid receptor (GR) heterozygous mice (GR(+/- )) represent a valuable animal model for major depression. GR(+/- ) mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR(+/- ) animals.

Activation of glucocorticoid receptors increases 5-HT2A receptor levels.

Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding.

Nature vs. nurture: can enrichment rescue the behavioural phenotype of BDNF heterozygous mice?

In earlier experiments we have demonstrated that group-housing in a rather impoverished "standard" environment can be a crucial stress factor in male C57Bl/6 mice. The present study aimed at investigating the effect of combining a probable genetic vulnerability--postulated by the "Neurotrophin Hypothesis of Depression"--with the potentially modulating influence of a stressful environment such as "impoverished" standard housing conditions. For that purpose mice with a partial deletion of brain-derived neurotrophic factor (BDNF) were group-housed under standard and enriched housing conditions and analysed in a well-established test battery for emotional behaviours.

Evaluation of effects of previous exposure to an acute stressor before testing for depression-like behaviours in mice.

Test batteries are an essential and broadly used tool for behavioural phenotyping, especially with regard to mouse models of particular diseases, such as depression. Facing the problem of an often limited number of mutant animals, it therefore seems crucial to develop and optimise such test batteries in terms of an ideal throughput of subjects. This study aimed to characterize several common stressors, which are used for the investigation of depressive-like features with regard to their capability of each of them to affect performance in a subsequent behavioural test.

Mice that under- or overexpress glucocorticoid receptors as models for depression or posttraumatic stress disorder.

Modern molecular and pathophysiological concepts suggest that glucocorticoid receptors (GRs) play a crucial role for the pathogenesis, course and therapy of affective or emotional disorders. Specifically, an impairment of GR signaling has been associated with major depression, whereas overactivity or hyperresponsiveness of GRs have been conceptualized for posttraumatic stress disorder (PTSD). Recently, several research groups have generated transgenic mouse strains that under- or overexpress GRs, respectively.

CREB-regulated diurnal activity patterns are not indicative for depression-like symptoms in mice and men.

Activation of the transcription factor CREB by Ser142 phosphorylation is implicated in synchronizing circadian rhythmicity, which is disturbed in many depressive patients. Hence, one could assume that emotional behaviour and neuroendocrinological markers would be altered in CREB(S142A) mice, in which serine 142 is replaced by alanine, preventing phosphorylation at this residue. Moreover, associations of CREB Ser142 and seasonal affective disorder (SAD) might be detectable by the analysis of single-nucleotide polymorphisms (SNPs) in the CREB gene close to the Ser142 residue in SAD patients.

Glucocorticoid receptor transgenic mice as models for depression.

In the era of mutant mice generated as molecular in vivo models for complex pathogenetic and therapeutic aspects of particular human diseases, glucocorticoid receptor transgenic mice represent an interesting and promising tool. Animals carrying mutations of this receptor show alterations in the hypothalamic-pituitary-adrenal (HPA)-system, which are comparable to those observed in depressed patients. Furthermore, similarities that may model the human disease have been described on the behavioral and pharmacological level, which increase the impact of such mutants.