Metabolic and endocrine consequences of social stress in a visible burrow system

The visible burrow system (VBS) is an ethologically relevant model of social stress, which has been used to study the aggression of male rats in a social context. Previous studies using the VBS have established physiological, endocrine, and neurochemical characteristics associated with chronic social stress in dominant and subordinate animals. A critical criterion in establishing an animal model for research is the replication of findings and the independent validation of the model. Here, we independently confirm previously reported findings and include novel control groups that are important in dissociating the effects of chronic social stress from those resulting from group-housing the male rats in an “enriched environment”. Furthermore, we show that whereas the VBS model is useful for males, it is not effective for studies of females because they do not form dominance hierarchies when housed in groups. We also extend the use of the VBS model to examine the etiology of stress-induced anorexia and obesity, finding that weight loss in subordinate rats is attributable to decreased adipose and lean tissue, whereas in dominant rats, it is associated only with adipose tissue loss. Consistent with this, the adiposity hormones leptin and insulin are decreased in subordinates and, to a lesser extent, in dominants, compared with the controls. In summary, the VBS model of chronic social stress is an ethologically relevant animal model and provides a valuable tool for studies of stress-related conditions and pathologies.     

Defense changes in stress nonresponsive subordinate males in a visible burrow system

Dominant and subordinate male rats housed in a visible burrow system (VBS), and male controls each housed with a female, were run in a series of tests evaluating their response to threatening stimuli. Subordinates were later assessed as stress responsive (SRS) or nonresponsive (NRS) on the basis of plasma corticosterone response to restraint stress. In the tests using mildly threatening stimuli (handling, open field), NRS had longer latencies to show a righting response and reduced activity compared to SRS or (handling, open field) to dominants. There were no differences among the VBS groups in tests with more intense threat stimuli (cat odor, cat presentation). These results suggest that stressful social experience may produce a shift toward more passive and immobile forms of defense and that the experience of subordination may interact with individual differences characteristics of rats to exacerbate this shift. The hypothalamic-pituitary-adrenal (HPA) axis changes of NRS, manifested as reduced plasma corticosterone response to restraint, and previous findings of sharply reduced testosterone in these animals, along with their passive defensive behaviors, form a pattern that is suggestive of a biobehavioral "reactive" (as opposed to "proactive") coping style, and suggest that these behavioral and endocrine variables may show related changes even when altered by individual experience.     

Chronic social stress in the visible burrow system modulates stress-related gene expression in the bed nucleus of the stria terminalis

Prolonged social subjugation produces physiological indices of chronic stress in rats. In the current study, we examined the impact of social stress on glutamic acid decarboxylase (GAD) isoforms, corticotropin-releasing hormone (CRH) and vasopressin mRNA expression in forebrain stress circuitry, using the visible burrow system model of dominance-subordination. Subordinate male rats develop behavioral and neuroendocrine changes consistent with exposure to chronic stress, including marked loss of body weight and elevation of basal plasma corticosterone relative to dominant rats. Forebrain GAD65, GAD67, CRH and vasopressin mRNA expression in central stress-regulatory circuits were examined by in situ hybridization. Elevated CRH mRNA was observed in the oval nucleus of the bed nucleus of the stria terminalis (BST) of subordinate males. In contrast, GAD67 expression was decreased in the interfascicular nucleus of the BST in both the subordinate and dominant rats compared to non-burrow control rats. No changes in CRH, GAD or vasopressin were observed in amygdaloid nuclei, other BST nuclei or in the hypothalamic paraventricular nucleus. Collectively, these data suggest that exposure to the visible burrow system attenuates BST GAD expression regardless of social status, whereas the enhanced physiological responses to social stress seen in subordinates may be associated with enhanced CRH expression in the oval nucleus of the BST.     

Activity rhythms and photoperiodism of Syrian hamsters in a simulated burrow system

Male Syrian hamsters were housed in simulated burrows in order to investigate (a) how these nocturnal, fossorial rodents entrain to the prevailing light:dark cycle in this semi-natural habitat and (b) the response of the reproductive system to environmental illumination. The burrow emergence activity of hamsters housed in simulated burrows was compared to the running wheel activity of animals maintained in standard cage conditions. The activity rhythm was similar in both measuring devices. The data suggested that in a natural environment hamsters are only exposed to light for short amounts of time each day. To determine whether brief photoperiodic stimulation could alter the phase angle of entrainment and/or the reproductive condition, burrow housed animals were exposed to a supplemental 30-second light pulse during specified clock hours of the dark period on a daily basis. These light pulses induced a phase shift and maintained a long day reproductive response in what was otherwise a short photoperiod.     

Twenty-two kHz alarm cries to presentation of a predator, by laboratory rats living in visible burrow systems.

When a cat was presented to groups of 3 male and 2 female laboratory rats in the open area of a visible burrow system, the rats retreated to the burrow system and showed high levels of 18-24 kHz ultrasonic cries during the cat presentation and for 30 min following removal of the cat. Latency to make ultrasonic vocalizations, durations of these vocalizations, and duration in the burrow systems were all strikingly and reliably different during and after cat exposure in comparison to similar periods with a control (stuffed cat toy) stimulus. However, when individual rats were exposed to a cat in an open area of similar size, ultrasonic cry production was minimal. Also rats exposed individually to a cat in an apparatus providing an escape chamber similarly showed no ultrasonic cries, indicating that concealment per se is not a sufficient condition for their appearance. These results suggest that the production of ultrasonic vocalizations during and after exposure to a predator is greatly facilitated by the presence of familiar conspecifics, and may serve as alarm cries. While the alarm cry hypothesis also suggests a possible function for 18-24 kHz ultrasounds in the context of copulation and intraspecies aggression, the sonographic and functional relationships among the cries emitted in these different situations remain to be analyzed.     

Activity rhythms of hamsters in a single cage compared to a simulated burrow system

A method for measuring activity of hamsters using a stabilimeter at a 1 second sampling rate with data computer recorded as 5 minutes integrated values was developed. In a single cage without a running wheel a consistent pattern for activity was observed, consisting of (a) low levels of daytime activity until one or two hours before lights off when activity increased significantly; and (b) a peak of nocturnal activity in the first hour of the dark cycle. The inclusion of a running wheel increased and altered significantly the pattern of nocturnal activity. In further experiments animals were housed in two linked cages, one acting as light-proof burrow and the other exposed to light. Measurements were recorded from each cage independently and from two position detectors in the interconnecting tunnel. The results showed: (a) total activity, i.e., the summation of activity in both cages, was not different from activity in a single cage system; (b) low daytime activity was composed of prolonged periods of rest in the burrow plus short periods of activity in the exposed cage; the increased activity one hour before lights off was localised to the light-proof burrow; and (c) after lights off, the animals began to spend increasing periods of time in the exposed cage reaching a maximum after one hour. Replacing artificial with natural light did not change the principal features of behaviour.     

Intensity of aggressive interactions modulates testosterone in male marmosets

Androgen is associated with the expression of male-typical behavior, including aggressive behavior, but high levels of androgen may be incompatible with other behavioral systems, such as paternal care. In a variety of species of birds that display paternal care, testosterone (T) levels in males are maintained at low levels, and these levels rise only in response to direct agonistic challenges. This idea has not been thoroughly studied in mammals with biparental care, and we exposed male marmosets (Callithrix kuhlii), a monogamous and biparental primate to aggressive interactions with unfamiliar intruders. Urinary levels of T and cortisol (CORT) were monitored prior to and following these interactions. Baseline T was not correlated with variation in aggression in either residents or intruders, and CORT was not affected by the encounters. However, males responded to an encounter with male intruders with changes in T that correlated with the level of aggression displayed by the resident male during the trial. Encounters with male intruders that elicited high frequencies of aggressive displays by the male resident were associated with increased T 2-6 h and 24 h following the encounter, and encounters that had few aggressive displays resulted in no change or a decrease in T concentrations. Intruders did not demonstrate a significant relationship between T and aggression. Thus, the magnitude of the hormonal response is dependent on the intensity of aggression during a male-male encounter, suggesting that elevated androgens are likely to be a consequence, rather than a cause, of aggressive interactions in marmosets.     

Neuroendocrine responses in free-living female and male lizards after aggressive interactions

Although female aggression is found in many species and in a variety of contexts, little is known about its physiological bases. To compare neuroendocrine responses to aggression in females and males, we staged aggressive interactions between free-living territorial mountain spiny lizards and same-sex intruders and measured brain monoamines, plasma steroid hormone levels, and plasma glucose levels. Both females and males that had participated in a staged aggressive interaction had similar changes in serotonin (5-HT) activity in telencephalic tissue punches as indicated by a lowered ratio of forebrain:brainstem 5-HT concentrations. In addition, both females and males had elevated plasma corticosterone (B) after an aggressive interaction when compared to controls. The only difference detected between males and females was that females had a higher ratio of forebrain:brainstem norepinephrine (NE) concentrations throughout the brain compared to males. Together, these data indicate that acute neural and hormonal responses that accompany aggressive interactions in females are similar to those in males.     

Cannabinoids and reward: interactions with the opioid system

There is currently substantial evidence that Cannabis sativa derivates act on brain reward in a way very similar to other drugs of abuse and exert numerous pharmacological effects through their interaction with various neurotransmitters and neuromodulators. Among them, the endogenous opioids seem to play an important role in modulating the addictive properties of cannabinoids. Given the plethora of research activity on such a topic, this brief review is necessarily focused on cannabinoid/opioid interaction in reward-related events and restricted to the recent literature. Recent findings from our and other laboratories concerning cannabinoid reinforcing effects as revealed by behavioral animal models of addiction are here summarized. Evidence is then provided demonstrating a functional cross-talk between the cannabinoid and opioid systems in the mutual modulation of the addictive behavior; accordingly, very recent data from transgenic mice lacking either the cannabinoid CB1 or opioid receptors are also presented. Finally, the role of the endogenous cannabinoid system in relapse to opioids is investigated by means of extinction/reinstatement animal models following a period, even prolonged, of drug abstinence. Altogether, the reviewed studies provided a better understanding of the neurobiological mechanisms involved in cannabinoid actions and revealed a bidirectional interaction between the endogenous cannabinoid and opioid systems in reward that extends to central mechanisms underlying relapsing phenomena. Challenges for the future involve elucidation of the neuroanatomical substrates of cannabinoids action, even in light of the therapeutic potential of these compounds.     

Parents' aggressive influences and children's aggressive problem solutions with peers.

This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with same-sex parents' actual marital aggression. For children with mothers who exhibited low actual marital aggression, mothers' aggressive solutions to hypothetical situations corresponded with children's tendencies to propose aggressive but not assertive solutions. In a 3-way interaction, fathers' aggressive solutions to peer scenarios and marital aggression, combined, exacerbated girls' aggressive problem solving but had the opposite effect for boys. We address the complexity, particularly with respect to parent and child gender combinations, in understanding parents' aggressive influences on children's peer relationships.     

Neuroendocrine-immune system interactions in amphibians

Amphibians are ancient creatures valued by biologists and naturalists around the world. They share with all other vertebrates a complex neuroendocrine system that enables them to flourish in a variety of aquatic and semiaquatic environments. Studies from a number of laboratorie shave demonstrated that the immune system of amphibian species is nearly as complex as that of mammals. Yet for reasons that are not well understood, amphibian species are facing greater survival challenges than in the recent past. This article will review our current understanding of the neuroendocrine immune system interactions in amphibians and address the question of whether environmental stressors may contribute to immunosuppression and amphibian declines.     

基于中国数字化人体的虚拟解剖学系统的建立

目的:研究数字化虚拟解剖系统有效地解决解剖学教学中面临的标本奇缺、标本破坏、教学环境限制等众多问题。方法:基于中国数字化人体数据集(CVH),联合山东数字人科技股份有限公司,通过数据分割、计算机三维重建、模型平滑贴图和软件系统构建开发,构建了中国首套基于真实人体数据的虚拟解剖系统。结果:该虚拟解剖系统包括断层解剖、系统解剖和局部解剖模块,提出了新的解剖学教学模式和教学理念,使医学生和低年资医生能随时随地进行系统解剖学、局部解剖学、断层解剖学甚至神经解剖学等多项课程的学习以及临床手术培训。结论:该软件系统操作环境舒适,无福尔马林等有害物质的吸入,能充分保障解剖学教学质量,提高学员学习效率,增强学习兴趣,提高学员三维空间想象能力,能带来新的一轮解剖学教学革命。     

Age-associated alterations in sympathetic neural interactions with the immune system

We have examined age-related alterations in sympathetic noradrenergic (NA) innervation in primary and secondary lymphoid organs from mouse and rat. As the thymus involuted with age, the density of NA innervation and norepinephrine (NE) concentration increased markedly. Total thymic NE was not altered significantly with age, suggesting that NA innervation is maintained as the thymus involutes. In the rat spleen, NA innervation and NE concentration were diminished with age. Enhanced antibody responses and in vitro proliferation to a T-dependent protein antigen were observed following selective destruction of NA nerve fibers with the neurotoxin 6-hydroxydopamine (6-OHDA), demonstrating that the diminished NA innervation in the aged spleen is capable of signaling the immune system. Plasticity of NA nerves in old rats was demonstrated following lesioning with 6-OHDA and in intact rats treated with -deprenyl, a monoamine oxidase B inhibitor. These age-related alterations in NA innervation of lymphoid organs occur concurrently with age-associated changes in immune function. Understanding the functional relationship between these two physiological systems in aging will contribute to a greater understanding of sympathetic nervous system regulation of immune function.     

Sexual interactions between estrous female rats and castrated male rats treated with testosterone propionate or estradiol benzoate

Estrous female rats display 'precopulatory behaviors' such as ear wiggling and hopping/darting when castrated males treated with testosterone propionate (TP) are placed in their vicinity and before copulatory interactions have taken place. Castrated males treated with estradiol benzoate (EB) do not elicit these precopulatory behaviors in advance of copulatory interactions. It therefore seemed of interest to study females' sexual behavior with castrated males treated with TP or EB when males or females had primary control over the temporal patterning of the behavior. Unrestrained sexual behavior (= male control) with EB-treated males was characterized by large numbers of intromissions and long periods of time preceding ejaculation, as compared with interactions with TP-treated males. The temporal pattern of sexual behavior did not change importantly when the males were tethered (= sexual behavior controlled by females). When given a choice between two sexually active castrated and tethered males, one treated with TP and the other with EB, estrous females 'preferred' EB-treated animals in various respects. Fewer interactions occurred with, and less time was spent in the vicinity of, TP-treated males over prolonged observation periods (115-135 min). The preference for EB-treated males disappeared, and TP- and EB-treated animals became equally attractive, when the vaginal opening of the female animals was covered with adhesive tape to prevent the occurrence of penile intromissions during mounting. It is concluded that female control over copulatory behavior does not necessarily change the females' sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetic analysis of monoclonal antibody-antigen interactions with a new biosensor based analytical system.

An automated biosensor system for measuring molecular interactions has been used to study the kinetics of monoclonal antibody-antigen reactions. The system combines a microfluidic unit in contact with a sensor surface for surface plasmon resonance detection. The specificity of the surface is determined by the operator. Antibody or antigen is immobilised in a dextran matrix attached to the sensor surface. The interaction of matrix bound antibody or antigen with the corresponding partner in solution is monitored in real time. None of the interacting molecules needs to be labelled and it is not necessary to determine the concentration of the the matrix bound component in advance. Two systems were studied: matrix bound monoclonal antibodies (MAbs) interacting with HIV-1 core protein p24 and immobilised aminotheophylline reacting with MAbs. Control of the amount of immobilised ligand and reusable sensor surfaces permits the comparison of different MAbs reacting with antigen under almost identical conditions. Differences in affinity and reaction rates are immediately apparent. The calculated association rate constants for p24 MAbs ranged from 3 x 10(4) - 7.4 x 10(5) M-1 s-1 and for theophylline MAbs association rate constants as high as 1 x 10(6) M-1 s-1 were encountered. The calculated dissociation rate constants were in the region 2 x 10(-4) s-1 to 2 x 10(-2) s-1.     

Rhabdoid cholangiocarcinoma: a variant of cholangiocarcinoma with aggressive behavior

A rhabdoid cholangiocarcinoma is a very rare variant of sarcomatous cholangiocarcinomas. Here, we report a vimentin positive cholangiocarcinoma showing rhabdoid features in the entire tumor, with a very aggressive behavior. A 41-year-old woman was admitted to our hospital due to a huge hepatic mass. The resected liver revealed a 17 x 15 cm sized solid mass with extensive necrosis and an infiltrative border. On microscopic examination, the entire tumor was composed of loosely cohesive round to polygonal cells, with rhabdoid features having abundant eosinophilic glassy cytoplasm and eccentrically located vesicular nuclei. Some tumor cells contained intracytoplasmic mucin vacuoles, but definite areas of glandular differentiation or spindle cell were not found. Immunohistochemical staining showed a diffuse strong positive reaction to pan-cytokeratin and vimentin, and focal positivity for the carcinoembryonic antigen. Other immunohistochemical stainings for cytokeratin 7, cytokeratin 20, S-100 protein, HMB-45, desmin, alpha-smooth muscle actin, c-kit, CD34, alpha-fetoprotein, anti-hepatocyte antigen, chromogranin and synaptophysin were all negative. After two months, the patient developed a local recurrence along the resection margin, and multiple hematogenous metastases to the lung and liver were seen on the follow-up CT scan.