Social status differentiates rapid neuroendocrine responses to restraint stress

Male Anolis carolinensis that win aggressive interactions mobilize neuroendocrine responses to social stress more rapidly than defeated lizards. We initially examined temporal patterns of neuroendocrine response to restraint stress in lizards of unknown status, and then investigated whether winning males respond more rapidly to this non-social stressor. Size-matched male pairs interacted to establish social status, and then were returned to individual home cages for 3 days. Plasma and brains were collected from non-restrained dominants and subordinates, and from a non-interacting control group. Additional groups of dominants and subordinates underwent 90 s restraint stress, with plasma and brains collected either immediately or 300 s after restraint. In lizards of unknown social status restraint stimulated rapid monoaminergic responses in nucleus accumbens, hippocampus, amygdala, and locus ceruleus, with delayed responses seen in VTA and raphé. Non-restrained dominants and subordinates had lower levels of raphé serotonergic activity and lower hippocampal dopaminergic activity 3 days after interacting, compared to controls. Dominants had higher corticosterone levels, both immediately and 300 s after restraint, than either non-restrained dominants or restrained subordinates. Restraint induced higher raphé serotonergic activity in dominants. However, subordinates also showed rapid responses to restraint; exhibiting lower hippocampal dopamine (DA) levels than non-restrained subordinates. At 300 s after the stress, amygdalar serotonin levels increased in dominants, while subordinates showed higher amygdalar DA levels. These results suggest that stressful aggressive interactions will not only alter basal neurochemical activity, but also influence neuroendocrine responses to non-social stressors according to individual social status.     

Cross-fostering Effects on Weight,Exploratory Activity,Acoustic Startle Reflex and Corticosterone Stress Response in Norway Gray Rats Selected for Elimination and for Enhancement of Aggressiveness Towards Human

Two rat lines, one tame, the other aggressive, differing by many behavioral features and stress reactivity were developed by long-term selection of wild gray rats for elimination and enhancement of aggressiveness towards humans. The aim of this work was to study the role of the maternal environment in the expression of these differences between the two rat lines using the cross-fostering paradigm. Fostering of tame rats of both sexes by aggressive mothers and aggressive females by tame mothers was without effect on behavior score towards humans, but the cross-fostered aggressive males had a small, yet significant, increase in aggressiveness score. Cross-fostering revealed that exploratory behavior in the hole-board test and the acoustic startle amplitude were weakly affected by maternal interactions, although there was an effect on body weight and on the stress corticosterone response. Body weight was decreased in tame males fostered by aggressive mothers only and it was increased in cross-fostered aggressive rats of both sexes. Fostering of tame males and females by an aggressive mother enhanced almost twofold the corticosterone response immediately after stress, while fostering of aggressive ratlings of both sexes by a tame mother was without effect. The current results demonstrated that the maternal postnatal environment had no substantial effect on the behavioral responses of both tame and aggressive rats, but it possibly contributed to the development of the corticosterone response to restraint stress in the tame, and not the aggressive rats, i.e. these effects of cross-fostering were dependent on ratling genotype. Edited by Tamara Phillips.     

Changes in markers of neuronal and glial plasticity after cortical injury induced by food restriction

The regenerative capacity of the adult central nervous system is limited. We investigated whether short-term food restriction (FR; 50% of the daily food intake lasting 3 months) modulates processes of brain plasticity after cortical injury. Quantitative changes of growth-associated protein 43 (GAP-43) and synaptophysin (SYP) mRNA levels in the ipsilateral cortex of the adult rat during the recovery period (from 2 to 28 days) after injury were investigated by real-time RT-PCR. Using Western blot and immunohistochemical analyses we examined the levels and localization of proteins involved in neuronal plasticity, SYP and GAP-43, as well as glial fibrillary acidic protein (GFAP), a marker of glial plasticity. A marked rise in GAP-43 and SYP immunoreactivity observed in the FR group on the 7th day after injury pointed to increases in axonal branching and synapses in the cortex surrounding the lesion. The appearance of reactive astrocytes was accompanied by the absence of immunoreactivity for GAP-43 and SYP in ad libitum fed animals. This finding supports the hypothesis that morphological hypertrophy of astrocytes associated with GFAP synthesis is responsible either directly or indirectly for the inhibitory role of activated glia on axonal regeneration. Examination of the effects of FR on serum corticosterone and glucose concentrations and GAP-43, SYP and GFAP expression revealed that FR facilitated recovery of the injured region by attenuating reactive astrogliosis and enhancing the expression of neuronal plasticity markers.     

Protective effects of peony glycosides against corticosterone-induced cell death in PC12 cells through antioxidant action

Aim of the study

Previous studies in our laboratory have shown that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. However, the molecular mechanism by which TGP exerts antidepressant-like effect is not fully understood. This study examined the protective ffects of TGP against corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells and ts possible mechanisms.

Materials and methods

The direct antioxidant effect of TGP was investigated by using a 2,2′-azinobis-(3-ethylbenzothiazoline- 6-sulphonic acid) (ABTS) radical cation-scavenging assay in a cell-free system. PC12 cells were treated with 200 μM of corticosterone in the absence or presence of TGP in varying concentrations for 48 h. Cell viability, lactate dehydrogenase (LDH) activity, intracellular reactive oxygen species (ROS) level, malondialdehyde (MDA) content, glutathione (GSH) content, superoxide dismutase (SOD) activity, and catalase (CAT) activity were then determined.

Results

TGP displayed antioxidant properties in the cell-free system, and the IC50 value in the ABTS radical cation-scavenging assay was 9.9 mg/L. TGP treatment at increasing doses (1-10 mg/L) protected against corticosterone-induced cytotoxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with decreases in the intracellular ROS and MDA levels, and increases in the GSH level, SOD activity, and CAT activity in corticosterone-treated PC12 cells.

Conclusion

The results suggest that TGP has a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action.     

Yolk testosterone and corticosterone in hierarchical follicles and laid eggs of Japanese quail exposed to long-term restraint stress

Environmental and behavioural stimuli experienced by egg-laying female birds contribute to intra- and inter-female differences in hormones in the egg yolk with consequences for offspring development. The understanding of physiological mechanisms underlying yolk hormone deposition can aid progress in this field. In our study, we measured the concentration of testosterone and corticosterone in hierarchical follicles and egg yolks of Japanese quail in control and chronic stress conditions. Experimental females were reared under hypodynamia, a model situation for restraint stress, from day 3 to 63 days of age. For yolk hormone analysis, four largest follicles of ovarian hierarchy (F1-F4), eggs present in the oviduct and eggs laid on the day before were collected. In chronically stressed birds, yolk testosterone concentrations decreased from F2 onwards, while yolk corticosterone content was increased from the beginning to the end of egg formation. The follicular profile of hormones suggested testosterone transfer into the yolk directly from granulosa and theca cells, with the highest accumulation during a period 48-72 h before laying the egg. Yolk corticosterone was accumulated from maternal plasma preferentially in early stages of follicular development under control conditions and also in last stages of egg formation under stress conditions. These specific patterns of hormone deposition indicate periods when stimuli experienced by female can substantially modify hormonal content of eggs. Lower testosterone and increased corticosterone yolk concentrations in stressed quail may represent signals mediating information about adverse environmental conditions from the mother to progeny.     

Distribution and time course of corticosterone excretion in faeces and urine of female mice with varying systemic concentrations

Quantification of corticosterone metabolites excreted in faeces and urine is increasingly being used for assessment of preceding corticosterone concentrations in the circulation. This is a promising approach to non-invasive stress assessment in laboratory rodents. It is however unknown whether the proportions of corticosterone metabolites excreted in faeces and urine may differ, depending on the concentration of corticosterone in blood. This uncertainty undermines the applicability of urinary and faecal corticosterone metabolite measurements as biomarkers for stress. Therefore, the terminal distribution and time course of corticosterone excretion, after intravenous injection of varying corticosterone concentrations, was investigated in female mice. Female BALB/c mice excreted 60% of all corticosterone in the urine with an approximate delay of 5 h from tail vein administration. The remaining 40% were excreted in faeces, with an approximate delay of 9 h from administration. The faecal/urinary excretion ratio, as well as time course of excretion, remained unaltered by administration of various doses of corticosterone covering the entire physiological range of serum corticosterone. Although currently untested for other strains of mice and species of animals, these findings add credence to the utility of faecal and urinary corticosterone as non-invasive biomarkers for physiological stress.     

Hormonal correlates of breeding behavior and pouch color in the Magnificent Frigatebird, Fregata magnificens

It is well known that testosterone (T) influences the expression of the behavior and many sexual traits during reproduction in vertebrates. However, patterns of circulating concentrations of T vary tremendously across free-living populations. Here the profiles of plasma T levels in the Magnificent Frigatebird, Fregata magnificens, are presented during the courtship, incubation and chick rearing stages of breeding. In addition, the predicted interrelationship of T and the expression of a sexually selected trait, the red gular pouch of males is investigated. Plasma levels of corticosterone (Cort) are reported in relation to the demands of breeding conditions in colonies. Blood samples were obtained from 26 males and 32 females in the 1993-1994 breeding season and 41 courting males in 1997. Pouch color and size were also estimated in these males. As expected, T levels changed across the breeding stages: birds showed high levels of T during courtship and much lower circulating levels during incubation and chick rearing. Consistent with the expected effect of T, individual pouch color and size correlated with circulating levels of this hormone. In this highly dimorphic species no correlation was found between T and body condition or tail asymmetry. Cort, in contrast, did not change across the three reproductive stages.     

普萘洛尔对应激大鼠行为、血清皮质酮和海马形态学的影响

目的观察普萘洛尔对慢性轻度不可预知性应激(CUMS)模型大鼠急性应激前后行为、血清皮质酮水平、海马DG区和CA3区形态学的影响。方法随机将健康成年Wistar雄性大鼠30只分为空白对照组、CUMS组、普萘洛尔处理组各10只。空白对照组大鼠不施加任何处理因素,其他组大鼠经过21?d CUMS暴露制作模型,普萘洛尔组大鼠于每次应激前0.5?h给予普萘洛尔混悬液灌胃。造模结束后,于第22天从3组大鼠中各随机抽取半数大鼠给予一定强度电击,应激结束后2?h取血,采用放射免疫法检测大鼠血清皮质醇的含量换算成皮质酮含量,脑区石蜡切片行HE染色。结果CUMS组大鼠呈现明显的主动活动和探索行为能力下降,海马DG区和CA3区形态学病理改变严重。与对照组比较,普萘洛尔组大鼠急性应激前皮质酮水平明显升高,急性应激后大鼠皮质酮水平显著降低,不能抑制海马DG区和CA3区病理改变,且有加重趋势。结论普萘洛尔可缓解应激导致的焦虑情绪,并降低个体遭遇急性应激时皮质酮的调动。     

Cytotoxicity and decreased corticosterone production in adrenocortical Y-1 cells by 3-methylsulfonyl-DDE and structurally related molecules

The persistent environmental pollutant 3-methylsulfonyl-DDE (3-MeSO₂-DDE) undergoes bioactivation by cytochrome P450 11B1 (CYP11B1) in the adrenal cortex of several animal species in vivo and causes decreased glucocorticoid production and cell death in the zona fasciculata. This study presents extended investigations of the cytotoxic and endocrine disrupting effects of 3-MeSO₂-DDE and some structurally related molecules in the mouse adrenocortical cell line Y-1. Both 3-MeSO₂-DDE and, to a lesser extent, 3,3′(bis)-MeSO₂-DDE decreased corticosterone production and produced CYP11B1-dependent cytotoxicity in Y-1 cells. Neither 2-MeSO₂-DDE nor p,p′-DDE had any significant effect on either cell viability or corticosterone production, indicating that the presence and position of the methylsulfonyl moiety of 3-MeSO₂-DDE is crucial for its biological activity. The adrenocortical toxicant o,p′-DDD decreased corticosterone production but was not cytotoxic in this cell line. None of the compounds altered Cyp11b1 gene expression, indicating that 3-MeSO₂-DDE inhibits CYP11B1 activity on the protein level.     

Cadmium exposure during pregnancy reduces birth weight and increases maternal and foetal glucocorticoids

Cadmium exposure induces low birth weight through unknown mechanisms. Since low birth weight is associated to foetal exposure to high glucocorticoids (GC) concentrations, we hypothesized that low birth weight induced by prenatal exposure to Cd²⁺ is, at least in part, mediated by higher foetal exposure to GC, specifically corticosterone, the main active GC in rodents. Pregnant rats were exposed to different dose of CdCl₂ administered in drinking water during the whole pregnancy period. At term, corticosterone was measured by enzyme immunoassay in maternal and foetal blood and in placental tissues. Cadmium was determined in placentas, maternal tissues (liver and kidney) and foetuses by inductively coupled plasma-mass spectrometry (ICP-MS). Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity and expression were determined by a radiometric conversion assay and quantitative RT-PCR respectively. Results demonstrated that 50 ppm of Cd²⁺, which was accumulated in different maternal tissues but not in the foetus, reduced pup birth weights and increased plasma corticosterone concentrations, both in mother and foetus. Placental 11β-HSD2 activity and expression did not change by the treatment. We conclude that 50 ppm of Cd²⁺ administered during pregnancy, increase foetal corticosterone concentrations due, probably, to alterations of the regulatory mechanisms of placental barrier to GC causing a mild but significant reduced birth weight.