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Different stress-related phenotypes of BALB/c mice from in-house or vendor: alterations of the sympathetic and HPA axis responsiveness.

ABSTRACT: BACKGROUND: Laboratory routine procedures such as handling, injection, gavage or transportation are stressful events which may influence physiological parameters of laboratory animals and may interfere with the interpretation of the experimental results. Here, we investigated if female BALB/c mice derived from in-house breeding and BALB/c mice from a vendor which were shipped during their juvenile life differ in their HPA axis activity and stress responsiveness in adulthood. RESULTS: We show that already transferring the home cage to another room is a stressful event which causes an increased HPA axis activation for at least 24 hours as well as a loss of circulating lymphocytes which normalizes during a few days after transportation. However and important for the interpretation of experimental data, commercially available strain-, age- and gender-matched animals that were shipped over-night showed elevated glucocorticoid levels for up to three weeks after shipment, indicating a heightened HPA axis activation and they gained less body weight during adolescence. Four weeks after shipment, these vendor-derived mice showed increased corticosterone levels at 45-min after intraperitoneal ACTH challenge but, unexpectedly, no acute stress-induced glucocorticoid release. Surprisingly, activation of monoaminergic pathways were identified to inhibit the central nervous HPA axis activation in the vendor-derived, shipped animals since depletion of monoamines by reserpine treatment could restore the stress-induced HPA axis response during acute stress. CONCLUSIONS: In-house bred and vendor-derived BALB/c mice show a different stress-induced HPA axis response in adulthood which seems to be associated with different central monoaminergic pathway activity. The stress of shipment itself and/or differences in raising conditions, therefore, can cause the development of different stress response phenotypes which needs to be taken into account when interpreting experimental data.

SUBMITTER: Olfe J

PROVIDER: S-EPMC2845127 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Different stress-related phenotypes of BALB/c mice from in-house or vendor: alterations of the sympathetic and HPA axis responsiveness.

Olfe Jakob J Domanska Grazyna G Schuett Christine C Kiank Cornelia C

BMC physiology 20100309

<h4>Background</h4>Laboratory routine procedures such as handling, injection, gavage or transportation are stressful events which may influence physiological parameters of laboratory animals and may interfere with the interpretation of the experimental results. Here, we investigated if female BALB/c mice derived from in-house breeding and BALB/c mice from a vendor which were shipped during their juvenile life differ in their HPA axis activity and stress responsiveness in adulthood.<h4>Results</h ...[more]

PMID: 20214799

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Project description:BackgroundAlterations of hypothalamic-pituitary-adrenal (HPA) axis activity and serotonergic signaling are implicated in the pathogenesis of human obesity and may contribute to its metabolic and mental complications. The association of these systems has not been investigated in human obesity.ObjectiveTo investigate the relation of HPA responsiveness and serotonin transporter (5-HTT) availability in otherwise healthy individuals with obesity class II or III (OB) compared to non-obesity controls (NO).Study participantsTwenty-eight OB (21 females; age 36.6 ± 10.6 years; body mass index (BMI) 41.2 ± 5.1 kg/m2) were compared to 12 healthy NO (8 females; age 35.8 ± 7.4 years; BMI 22.4 ± 2.3 kg/m2), matched for age and sex.MethodsHPA axis responsiveness was investigated using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test, and curve indicators were derived for cortisol and adrenocorticotropic hormone (ACTH). The 5-HTT selective tracer [11C]DASB was applied, and parametric images of the binding potentials (BPND) were calculated using the multilinear reference tissue model and evaluated by atlas-based volume of interest (VOI) analysis. The self-questionnaires of behavioral inhibition system/behavioral activation system (BIS/BAS) with subscales drive, fun-seeking and reward were assessed.ResultsOB showed significant positive correlations of ACTH curve parameters with overall 5-HTT BPND (ACTHAUC: r = 0.39, p = 0.04) and 5-HTT BPND of the caudate nucleus (ACTHAUC: r = 0.54, p = 0.003). In NO, cortisol indicators correlated significantly with BPND in the hippocampus (cortisolAUC: r = 0.59, p = 0.04). In OB, BAS reward was inversely associated with the ACTHAUC (r = -0.49, p = 0.009).ConclusionThe present study supports a serotonergic-neuroendocrine association, which regionally differs between OB and NO. In OB, areas processing emotion and reward seem to be in-volved. The finding of a serotonergic HPA correlation may have implications for other diseases with dysregulated stress axis responsiveness, and for potential pharmacologic interven-tions.

Project description:The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior. The purpose of this investigation was to study the age-related and individual features of the HPA axis response to acute stress exposure (ASE) under chronic CL in nonhuman primates that are known to differ in behavioral responsiveness to stress. Young and old female rhesus monkeys (with control standard behavior or anxiety and depression-like behavior) were exposed to CL (24 h light/day, 330-400 lux for 4 to 8 weeks). Control young and old monkeys were exposed to standard lighting (SL) with natural light during the day and darkness at night. All animals were subjected to ASE (restriction of mobility for 2 hours), functional tests with corticotrophin-releasing hormone and arginine-vasopressin, and study of circadian rhythms of cortisol and pineal melatonin secretion. For the first time an inhibitory effect of CL on the reaction of the adrenal cortex to ASE was revealed in all individuals, regardless of age and preexisting behavior stress reactivity, the mechanisms of which were age-dependent: due to inhibition of the pituitary ACTH secretion in young animals and mainly not affecting the ACTH secretion in old individuals. There were no significant changes in melatonin secretion both in young and old animals. The observed CL inhibition of adrenal cortical reactivity to ASE may be useful to correct increased vulnerability to ASE observed in individuals with preexisting anxiety and depression-like stress behaviors. On the other hand, the CL induced decrease in adrenal stress reactivity of behaviorally normal animals suggests a potential risk of reducing the adaptive capacity of the organism under conditions of continuous light exposure.

Project description:BackgroundSexual assault is implicated in several adverse psychological and physical health outcomes, including posttraumatic stress disorder (PTSD) and depression. Neurobiological research has shown variations related to the hypothalamic-pituitary-adrenal (HPA) axis, immune alterations, metabolic function, and brain circuitry. Although these mechanisms have been extensively studied, the results have demonstrated different outcomes in PTSD.MethodsWe compared the plasma adrenocorticotropin (ACTH) and salivary cortisol levels of fifty-eight women with PTSD developed after sexual assault to those of forty-four female controls with no history of trauma. We also evaluated the psychiatric diagnosis and symptom severity of PTSD and depression. The participants' clinical conditions were associated with their hormonal levels to assess whether symptom severity was related to hormonal imbalance.ResultsA large percentage of sexually assaulted women had PTSD and comorbid depression. The ACTH levels were higher in the PTSD group than the control group and increased as PTSD severity increased, considering depressive symptoms, measured by the Beck Depression Inventory (BDI) (p < 0.0001), as well as PTSD symptoms, measured by subscale D of the Clinician-Administered PTSD Scale (CAPS-5) (p = 0.045) and the CAPS-5 total scale (p = 0.026). Cortisol levels measured at 10 pm were higher for the PTSD group than the control group (p = 0.045, p = 0.037, respectively), and the cortisol awakening response showed elevated cortisol levels for the PTSD group.ConclusionsThese results show a correlation between symptom severity and HPA axis imbalance in patients with PTSD. Elevated ACTH and an elevated cortisol response in patients with comorbid depressive symptoms were the opposite of the expected response for patients with PTSD only. This association leads to the hypothesis that the neurobiological alterations of PTSD are related to the type of symptoms presented and their severity. These manifestations likely influence the disease course, prognosis and response to treatment. These outcomes highlight the need to discuss particular neurobiological alterations in patients with PTSD developed after sexual assault, mainly those with severe depressive symptoms.

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Different stress-related phenotypes of BALB/c mice from in-house or vendor: alterations of the sympathetic and HPA axis responsiveness.

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Different stress-related phenotypes of BALB/c mice from in-house or vendor: alterations of the sympathetic and HPA axis responsiveness.

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