Glucocorticoid receptor interaction with Hsp90 remains unaltered after whole body hyperthermia

The influence of 41 degrees C whole body hyperthermic stress on glucocorticoid receptor (GR) association with 90-kDa heat shock protein (Hsp90) in the rat liver cytosol was examined. Total cytosolic GR and Hsp90 concentrations, as well as the amount of Hsp90 co-immunoprecipitated with the GR were determined by quantitative Western blotting using BuGR2 as anti-GR and AC88 as anti-Hsp90 monoclonal antibody. After exposure of the animals to the heat stress, the level of cytosolic Hsp90 increased, while its ratio to apo-receptor within non-activated GR heterooligomeric complexes remained unaltered. Therefore, the Hsp90 recruitment by the GR was not dependent on Hsp90 total cytosolic concentration.     

慢性心理应激对大鼠淋巴细胞热休克蛋白70表达和凋亡的影响

为了探讨慢性心理应激对热休克蛋白70（Hsp70）、淋巴细胞的凋亡及其两者之间关系的影响,将实验SD大鼠分为对照组、中等强度心理应激组和高强度心理应激组。分别对三组大鼠给予相应的干预3周,采用流式细胞仪定量检测各组大鼠外周血淋巴细胞Hsp70的表达水平和凋亡量。结果发现,与对照组比较,中等和高强度心理应激组淋巴细胞内Hsp70表达水平显著增加;中等强度心理应激组凋亡量增加但没有出现统计学意义,高强度心理应激组淋巴细胞凋亡显著增加;中等强度心理应激组的淋巴细胞Hsp70表达与凋亡量变化成显著正相关,高强度心理应激组两者变化成不显著正相关。研究结果提示心理应激能诱发淋巴细胞Hsp70表达和凋亡升高,且随心理应激强度增加,Hsp70表达升高趋势减缓、凋亡量增加加剧,最终造成机体免疫损伤加深     

Hyperthermia impairs retrieval of an overtrained spatial task in the Morris water maze

Fifteen rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze (40 +/- 2 degrees C). Then retention of the spatial task was assessed immediately after raising core body temperature (Tc) to 42 or 40 degrees C or stabilizing at 37 degrees C (the normothermic control). The hyperthermic treatment order was counterbalanced according to a Latin-square design. Hyperthermia at 42 degrees C Tc significantly impaired spatial performance. Hyperthermic animals were cooled to normothermia (Tc = 37 degrees C) and spatial performance was tested again approximately 30 min later. Cooling resulted in a complete recovery of spatial performance. These results demonstrate that hyperthermia-induced amnesia can be obtained on an overtrained spatial-mapping strategy and cooling to normothermia initiates recovery of spatial performance.     

Hypothalamic-pituitary-adrenal axis dysregulation and behavioral analysis of mouse mutants with altered glucocorticoid or mineralocorticoid receptor function

Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that MRs in the limbic brain also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to more fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors.     

Differentiating the impact of episodic and chronic stressors on hypothalamic-pituitary-adrenocortical axis regulation in young women.

OBJECTIVE: The goal of this study was to examine the impact of episodic stress and chronic interpersonal stress on indices of HPA regulation. To explore the potential downstream consequences of altered HPA dynamics, the authors also assessed indicators of metabolic control and systemic inflammation. DESIGN: One hundred four medically healthy women between the ages of 15 and 19 participated. Following an in-depth interview of life stress, a sample of blood was drawn through antecubital venipuncture. Over the course of the next 2 days, participants gathered salivary cortisol samples. MAIN OUTCOME MEASURES: Cortisol morning response, cortisol daily output, glucocorticoid receptor (GR) mRNA, C-reactive protein (CRP), insulin, and glucose. RESULTS: The simple presence of episodic stress or chronic interpersonal stress was not reliably associated with cortisol output, GR mRNA, insulin, or glucose. When women were exposed to an episodic stressor in the midst of chronic stress they showed increased cortisol output and reduced expression of GR mRNA. By contrast, when women had low levels of chronic stress, episodic events were associated with decreased cortisol output and increased GR mRNA. Episodic and chronic stress also interacted to predict CRP, but not insulin or glucose. CONCLUSIONS: The impact of episodic stress is accentuated in the midst of chronic interpersonal stress and diminished in its absence. Simultaneous exposure to episodic and chronic stress may create wear and tear on the body, whereas exposure to episodic stress in the context of a supportive environment may toughen the body, protecting it against subsequent stressors.     

Intracerebroventricular Administration of Mineralocorticoid Receptor Antisense Oligonucleotides Attenuates Salt Appetite in the Rat

The anterior ventral third ventricle (AV3V) region of the brain contains high concentrations of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) that are important in the maintenance of body fluid and electrolyte balance as well as other physiological processes. Daily intracerebroventricular pulse injections of MR antisense oligonucleotides significantly suppressed deoxycorticosterone acetate (DOCA) induced salt appetite in a dose-related manner. Similar administration of GR antisense or scrambled/sense oligonucleotide into the third ventricle failed to inhibit salt appetite. Salt appetite aroused after adrenalectomy was not suppressed by MR antisense oligonucleotide treatments but was suppressed by an antisense oligonucleotide directed against the angiotensin II AT1 receptor subtype. Receptor binding analysis demonstrated that MR and GR oligonucleotide treatments each reduced their respective receptor subtypes. Finally, although GR antisense oligonucleotide treatment was ineffective in suppressing DOCA-induced salt appetite, this treatment did increase stress induced corticosterone release as well as delayed the recovery of corticosterone to basal levels after stress.     

慢性应激对大鼠行为和免疫细胞热休克蛋白70表达的影响

目的：研究慢性不确定应激对大鼠急性整体热水浴后外周血和脾脏免疫细胞热休克蛋白70（Heat shock protein 70, HSP70）表达的影响。方法：随机将大鼠分成慢性应激组和控制组（每组14只）。通过4周的慢性不确定性应激诱发实验组大鼠明显的抑郁行为,此期间控制组大鼠正常饲养。随后给予大鼠42度整体热水浴刺激,维持直肠温度41度25min。热刺激后6h,采用流式细胞仪测定大鼠外周血和脾脏免疫细胞HSP70 水平。结果：与控制组大鼠相比,慢性应激大鼠在急性热刺激后HSP70合成明显减少。控制组大鼠的所有被检测的免疫细胞热应激后HSP70合成均明显增加。相反,慢性应激大鼠仅在外周血的单核细胞和粒细胞检测到HSP70合成增加,同时升高的水平明显低于控制组大鼠。结论：慢性应激降低大鼠免疫细胞HSP70的热诱导反应,提示HSP70保护性作用减弱可能参与了慢性应激损害免疫细胞功能的生物学过程     

Identifying the information for the visual perception of relative phase

The production and perception of coordinated rhythmic movement are very specifically structured. For production and perception, 0 degree mean relative phase is stable, 180 degrees is less stable, and no other state is stable without training. It has been hypothesized that perceptual stability characteristics underpin the movement stability characteristics, which has led to the development of a phase-driven oscillator model (e.g., Bingham, 2004a, 2004b). In the present study, a novel perturbation method was used to explore the identity of the perceptual information being used in rhythmic movement tasks. In the three conditions, relative position, relative speed, and frequency (variables motivated by the model) were selectively perturbed. Ten participants performed a judgment task to identify 0 degree or 180 degrees under these perturbation conditions, and 8 participants who had been trained to visually discriminate 90 degrees performed the task with perturbed 90 degrees displays. Discrimination of 0 degree and 180 degrees was unperturbed in 7 out of the 10 participants, but discrimination of 90 degrees was completely disrupted by the position perturbation and was made noisy by the frequency perturbation. We concluded that (1) the information used by most observers to perceive relative phase at 0 degree and 180 degrees was relative direction and (2) becoming an expert perceiver of 90 degrees entails learning a new variable composed of position and speed.     

Thermal homeostasis in pregnant rats during heat stress.

Rats exposed to inescapable heat stress maintained a controlled hyperthermia while increasing heat loss by cutaneous vasodilatation and by grooming behavior. In nonpregnant rats, the evaporation of saliva groomed onto the body surfaces increased exponentially as a function of ambient temperature above 36 degrees C. This was associated with a decrease in the body temperature threshold for salivary secretion from the submaxillary gland, which then began at approximately the same body temperature as cutaneous vasodilatation. In addition, the pregnant rats maintained a lower level of controlled hyperthermia during heat stress than did nonpregnant rats. This appeared to result from a decreased production of metabolic heat, reduced insulation on the ventral surface, and an increased motivation to keep cool during heat stress. These changes met the increased need for thermolysis during pregnancy and provided for thermal homeostasis both in the pregnant rat and in the unborn fetuses.     

The effect of high ambient temperature on timing behavior in rats

The present experiments demonstrated a reliable within-session increase in rectal temperature (T(re)) at 25 degrees C during stable differential-reinforcement-of-low-rate (DRL) performance. The thermal response was found to be independent of the DRL value and reinforced DRL performance, but dependent on the state of the animal's deprivation. Exposure to a 35 degrees -C environment increased the post-session T(re) significantly above the 25 degrees -C post-session T(re) for seven of eight subjects. Response and reinforcement rate at 35 degrees C was found to be independent of DRL value, although it decreased as DRL value increased at 25 degrees C. A discriminative stimulus used to mark the end of the interval increased the reinforcement rate at 25 degrees C but provided no advantage at 35 degrees C. Measurement of the pattern of responding during DRL performance revealed increases in the proportion of long interresponse times at 35 degrees C. Reinforcement rate was found to decrease progressively at 35 degrees C, reaching a minimum within 40 to 50 min of the 90-min session. Visual observation of overt behaviors during DRL performance at 35 degrees C revealed a reduction in the frequency of overt behavior, characteristic of 25 degrees -C performance, and a time-dependent increase in the probability of an alternative set of behaviors.     

广东汕头大学高年级学生心理健康及压力调适研究

目的研究汕头大学高年级大学生心理压力特点及心理压力的调适。方法对128名毕业班的高年级大学生进行问卷调查,分析不同专业、性别与各压力的相关性,并了解其压力调适特点。结果大学毕业生的就业压力比其它压力重,不同专业大学生之间压力程度无显著差异。结论大学毕业生压力总体上仍属于轻度压力,在压力源中就业压力占主要地位,大学校园不应忽视对毕业生的就业指导及心理辅导。     

Visual search for orientation among heterogeneous distractors: experimental results and implications for signal-detection theory models of search

Three experiments tested a signal-detection theory (SDT) model of visual search (e.g., as described in J. Palmer, C. T. Ames, & D. T. Lindsey, 1993). In Experiment 1, participants searched for a 0 degrees line among distractors at (a) 30 degrees; (b) 1/3 at 30 degrees, 2/3 at 50 degrees; (c) 1/3 at 30 degrees, 50 degrees, and 70 degrees; and (d) 1/3 at 30 degrees, 2/3 at 70 degrees. The SDT model predicts improved performance in the more heterogeneous conditions, as some distractors are more discriminable from the target. In contrast, in Experiment 1 human performance degraded in the more heterogeneous conditions (c and d). In Experiment 2, sparser displays improved the performance of the SDT model. In Experiment 3, search for theta degrees among homogeneous theta + 20 degrees distractors was compared with search for theta degrees among theta+/-20 degrees distractors. Performance in the latter condition was often worse, relative to performance in the homogeneous condition, than predicted by the SDT model; however, this depended greatly on the identity of the target.     

The acquisition of movement skills: practice enhances the dynamic stability of bimanual coordination.

During bimanual movements, two relatively stable "inherent" patterns of coordination (in-phase and anti-phase) are displayed (e.g., Kelso, Am. J. Physiol. 246 (1984) R1000). Recent research has shown that new patterns of coordination can be learned. For example, following practice a 90 degrees out-of-phase pattern can emerge as an additional, relatively stable, state (e.g., Zanone & Kelso, J. Exp. Psychol.: Human Performance and Perception 18 (1992) 403). On this basis, it has been concluded that practice leads to the evolution and stabilisation of the newly learned pattern and that this process of learning changes the entire attractor layout of the dynamic system. A general feature of such research has been to observe the changes of the targeted pattern's stability characteristics during training at a single movement frequency. The present study was designed to examine how practice affects the maintenance of a coordinated pattern as the movement frequency is scaled. Eleven volunteers were asked to perform a bimanual forearm pronation-supination task. Time to transition onset was used as an index of the subjects' ability to maintain two symmetrically opposite coordinated patterns (target task - 90 degrees out-of-phase - transfer task - 270 degrees out-of-phase). Their ability to maintain the target task and the transfer task were examined again after five practice sessions each consisting of 15 trials of only the 90 degrees out-of-phase pattern. Concurrent performance feedback (a Lissajous figure) was available to the participants during each practice trial. A comparison of the time to transition onset showed that the target task was more stable after practice (p=0.025). These changes were still observed one week (p=0.05) and two months (p=0.075) after the practice period. Changes in the stability of the transfer task were not observed until two months after practice (p=0.025). Notably, following practice, transitions from the 90 degrees pattern were generally to the anti-phase (180 degrees ) pattern, whereas, transitions from the 270 degrees pattern were to the 90 degrees pattern. These results suggest that practice does improve the stability of a 90 degrees pattern, and that such improvements are transferable to the performance of the unpractised 270 degrees pattern. In addition, the anti-phase pattern remained more stable than the practised 90 degrees pattern throughout.     

Correlation between Changes in Stress-Induced Corticosterone Secretion and GR mRNA Levels

The current study was conducted to determine the potential relationship between stress-induced corticosterone secretion and corticosteroid receptor mRNA levels after 5 days of intermittent stress. In particular, we were interested in the rate at which animals terminate a stress response, and how this termination may be altered by repeated stress. Adult male Sprague-Dawley rats were subjected to either 5 days of restraint stress or 5 days of an unpredictable stress paradigm. Restraint-stress induced corticosterone secretion was measured on Days 1 and 5 in both groups, and animals were killed on Day 6. Glucocorticoid receptor (GR), and mineralocorticoid (MR) mRNA levels were determined using in-situ hybridization techniques. Five days of restraint stress caused an habituation of the plasma corticosterone response to stress measured 60 and 90 min post-stress initiation; this pattern of corticosterone secretion was not observed in the animals subjected to unpredictable stress. Five days of either stress paradigm did not alter MR mRNA levels measured within the hippocampus or GR mRNA levels within the hippocampus or the medial parvocellular division of the paraventricular nucleus of the hypothalamus (mpPVN). However, an individual's GR mRNA levels measured within the CA1/2 region of the hippocampus and the mpPVN were significantly correlated with the degree of habituation of the corticosterone response to stress measured on Day 5. This suggests that an increase in the rate of termination of the stress response and levels of GR within the hippocampus and mpPVN may be functionally related.     

Circulating leukocyte heat shock protein 70 (HSP70) and oxidative stress markers in rats after a bout of exhaustive exercise

A novel method to measure oxidative stress resulting from exhaustive exercise in rats is presented. In this new procedure we evaluated the erythrocyte antioxidant enzymes, catalase (CAT) and glutathione reductase (GR), the plasma oxidative attack markers, reactive carbonyl derivatives (RCD) and thiobarbituric reactive substances (TBARS). Muscular tissue damage was evaluated by monitoring plasma creatine kinase (CK) and plasma taurine (Tau) concentrations. Also, we monitored total sulphydryl groups (TSG) and uric acid (UA), and the level of the 70 kDa heat shock protein (HSP70) in leukocytes as a marker of oxidative stress. In the study we found a correspondence between erythrocyte CAT and GR activities and leukocyte HSP70 levels, principally 3 h after the acute exercise, and this suggested an integrated mechanism of antioxidant defense. The increase in levels of plasma Tau was coincident with the increasing plasma levels of CK and TBARS, principally after two hours of exercise. Thus tissue damage occurred before the expression of any anti-oxidant system markers and the monitoring of Tau, CK or TBARS may be important for the estimation of oxidative stress during exhaustive exercise. Furthermore, the integrated analyses could be of value in a clinical setting to quantify the extent of oxidative stress risk and reduce the need to perform muscle biopsies as a tool of clinical evaluation.     

The compression of perceived time in a hot environment depends on physiological and psychological factors

The human perception of time was observed under extremely hot conditions. Young healthy men performed a time production task repeatedly in 4 experimental trials in either a temperate (22 °C, relative humidity 35%) or a hot (42 °C, relative humidity 18%) environment and with or without a moderate-intensity treadmill exercise. Within 1 hour, the produced durations indicated a significant compression of short intervals (0.5 to 10 s) in the combination of exercising and high ambient temperature, while neither variable/condition alone was enough to yield the effect. Temporal judgement was analysed in relation to different indicators of arousal, such as critical flicker frequency (CFF), core temperature, heart rate, and subjective ratings of fatigue and exertion. The arousal-sensitive internal clock model (originally proposed by Treisman) is used to explain the temporal compression while exercising in heat. As a result, we suggest that the psychological response to heat stress, the more precisely perceived fatigue, is important in describing the relationship between core temperature and time perception. Temporal compression is related to higher core temperature, but only if a certain level of perceived fatigue is accounted for, implying the existence of a thermoemotional internal clock.     

Adrenergic and calcium modulation of the heart in stress: from molecular biology to function

There is strong evidence about the importance of catecholamines and calcium signaling in heart function. Also, interaction of these two systems is well documented. Catecholamines signal through adrenergic receptors, and further activate calcium transport either from the extracellular space, or from the intracellular calcium stores. This review summarizes current knowledge on catecholamine production in the heart, with special focus on the final enzyme in the catecholamine synthesizing pathway, phenylethanolamine N-methyltransferase (PNMT), in different cell types in the heart. Further, signaling through different types of adrenergic receptors in physiological conditions and after exposure to different stressors is discussed. Also, part of this review considers activation of an intracellular calcium transport system via inositol 1,4,5-trisphosphate receptor and to possible functional consequences in control and stress conditions.