Psychosocial stress affects pineal function in the tree shrew (Tupaia belangeri)

Using a recently developed commercially available radioimmunoassay the concentration of the principal melatonin metabolite 6-sulfatoxymelatonin (aMT6s) in the morning urine of male tree shrews was determined. Chronic social confrontation elicited a drastic increase of aMT6s excretion in subordinate tree shrews, whereas there was a tendency to reduced excretion of the melatonin metabolite in dominant animals. These results substantiate the function of the pineal gland in transforming stimuli from the social environment to endocrine information and, therefore, are indicative for the relevant role the gland may play in the physiological reactions to chronic psychosocial stress.     

环境压力对中国树鼩生殖生理影响的实验研究

目的： 探讨环境压力对中国树鼩生殖生理的影响。方法： 中国树鼩30只，随机分为3组，1组为对照组10只，2组8只，3组12只。实验组采用缩小饲育环境、增大同种性别动物密度的方法，用放免仪测定性激素水平，用光镜观察睾丸的组织结构。结果： 经分笼饲养21 d测定，2、3组动物血清睾酮（T）比1组分别低49.4%和80.3%（P<0.01）；雌三醇（E₂）水平各组间差异无显著；光镜观察发现，2组动物睾丸组织曲细精管在高倍镜下可见精原细胞与支持细胞网架；3组仅见少数几个精原细胞。结论： 环境压力能抑制中国树鼩睾酮形成，损伤睾丸组织结构。     

脑缺血及后适应对树鼩海马内质网应激信号分子PERK及GRP78的影响

目的:探讨脑缺血及后适应对树鼩海马内质网应激信号分子蛋白激酶R样内质网激酶(PERK)及葡萄糖调节蛋白78(GRP78)的影响及后适应的脑保护机制。方法:光化学反应诱导树鼩局部血栓性脑缺血,于脑缺血后3.5 h夹闭、打开缺血侧颈总动脉交替3个循环(每次5 min)以复制缺血后适应模型。HE染色观察缺血侧海马神经元损伤及超微结构变化,RT-PCR检测脑缺血及后适应不同时间海马组织PERK及GRP78 mRNA表达的变化,免疫组织化学法与Western blot法检测PERK及GRP78的蛋白定位及表达变化。结果:海马神经元随脑缺血时间延长而损伤加重,缺血24 h损伤最为严重,后适应可减轻损伤。脑缺血4 h、24 h及72 h PERK的mRNA及蛋白表达较假手术组增高(P0.05),后适应组与相应的缺血组相比,PERK的mRNA及蛋白表达减少,4 h、24 h差异显著(P0.05);脑缺血4 h、24 h及72 h GRP78的mRNA及蛋白表达与假手术组无明显差异,后适应24 h组较缺血24 h组表达增高(P0.05)。结论:树鼩局部血栓性脑缺血可激活缺血侧海马内质网应激反应,引起PERK/e IF2α信号转导通路中相关分子PERK的mRNA及蛋白表达增高。缺血后适应处理通过下调PERK、上调GRP78的表达,减轻内质网应激反应,减少神经元损伤,具有一定的脑保护作用。     

Interlaminar connections of tree shrew visual cortex.

The intracortical projections of neurons in layers II and upper III of tree shrew visual cortex were studied after terminal lesions in the supragranular layers of area 17. Examination for terminal degeneration was made using ultrastructural techniques. The majority of degenerating terminals were found in layers V and, to a lesser extent, VI, and were presynaptic to neural profiles in the following distribution: 80.5% on spines of small to medium size dendrites, 19% on dendrite shafts, and less than 1% on neuronal perikarya. Degenerating axons coursed in vertical bundles through layers III, IV, V and VI. These findings are similar to those previously described in rat visual cortex.     

Aging, stress and the hippocampus

Functional loss often occurs in many body systems (e.g., endocrine, cognitive, motor) with the passage of years, but there is great individual variation in the degree of compromise shown. The current focus on brain aging will continue because demographic trends indicate that the average lifespan will show a continued increase. There is increasing emphasis on understanding how aging contributes to a decline in brain functions, cognition being a prime example. This is due in part to the fact that dementias and other losses in brain function that sometimes accompany aging cause an obvious decline in the quality of life and these deficits are of more concern as the number of elderly increase. Stress also is a ubiquitous aspect of life and there is now a greater interest in understanding the role of stress and the stress response in brain aging. The key role of the hippocampus and its related brain structures in cognition, as well as in the feedback control of the response to stress, have made this brain area a logical focus of investigation for those interested in the impact of stress on brain aging. Here, we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretion patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this structure. We also examine the proposal that stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging through exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, plasticity, electrophysiological or neurochemical properties of neurons or glia. Although excessive levels of glucocorticoids are able to interfere with cognition, as well as hippocampal neuronal integrity, and aging is sometimes accompanied by an increase in these steroids because of inadequate feedback control of the HPA axis, none of these are a foregone consequence of aging. The general preservation of cells and the plastic potential of the hippocampus provide a focus for the development of pharmacological, nutritive or lifestyle strategies to combat age-related declines in the hippocampus as well as other brain areas.     

Ciliogenesis in photoreceptor cells of the tree shrew retina

 Transmission electron microscopy of the retinal cones from several prenatal, young postnatal and adult tree shrews (Tupaia belangeri) reveals that the centrioles, from which the ciliary precursors of the outer segments grow out, are not transported into a pre-existing inner segment, but are positioned under the apical plasma membrane of cone precursor cells all through the inner segment formation. Ciliogenesis starts before or on embryonic day 20 and thus precedes initial formation of the inner segment by 20 days, which is half the gestation period. Thus, the maturation of the outer segment covers a considerably longer period than has been previously described. Published observations from other mammals can be interpreted as conforming with the situation in Tupaia. In other vertebrates, compared to mammals, marked heterochronies do occur. In Tupaia, the centrioles and the cilium are located close to the central longitudinal axis of the photoreceptor precursor cell from the 20-day-old embryo to the 5-day-old juvenile. In this position the microtubule apparatus originating from the centrioles should be most effective in transporting the mitochondria into the inner segment. In the 12-day-old tree shrew, when transport of the mitochondria into the inner segment has been completed, centrioles and cilium have shifted into an eccentric position and the light-collecting megamitochondria have approached the disks of the outer segment. This eccentric position is maintained in all later developmental stages. In certain of the retinal areas of the adult Tupaia, the connecting cilia of neighbouring cones are always positioned on the same side of the inner segments. Accepted: 18 March 1997     

A lectin-histochemical study on the seminiferous epithelium of the northern smooth-tailed tree shrew (Dendrogale murina) and the Java tree shrew (Tupaia javanica)

Lectin-binding patterns in the testes of the northern smooth-tailed tree shrew, Dendrogale murina and Java tree shrew, Tupaia javanica were studied by light microscopy and compared the data with those of the common tree shrew. Four lectins (PNA, SBA, BPA and GS-II) were used in this study. Peanut (Arachis hypogaea) agglutinin (PNA), soybean (Glycine max) agglutinin (SBA) and Bauhinia purpurea agglutinin (BPA) showed a strong reaction in the acrosomal region from Golgi to acrosome-phase spermatids in three species of tree shrews. These lectins also showed a granular positive reaction in the cytoplasm from acrosome to maturation-phase spermatids in three species, except that BPA revealed no granular reaction (though it was positive) in the spermatid cytoplasm of the northern smooth-tailed tree shrew and that PNA revealed no reaction in the spermatid cytoplasm of the common tree shrew. While, Griffonia simplicifolia-II agglutinin (GS-II) showed a positive reaction in the acrosomal region of Golgi-phase spermatids in three species of tree shrews. Although GS-II was positive in the spermatocyte cytoplasm of three species, it showed granular in the northern smooth-tailed tree shrew and common tree shrew but not granular in the Java tree shrew. Thus, the lectin-binding patterns in testes were similar among three species belonging to the Order Scandentia. However, slight differences were also detected even among these phylogenetically-close species.     

Zinc,magnesium and NMDA receptor alterations in the hippocampus of suicide victims

Background

There is evidence for an association between suicidal behavior and depression. Accumulating data suggests that depression is related to a dysfunction of the brain's glutamatergic system, and that the N-methyl-d-aspartate (NMDA) receptor plays an important role in antidepressant activity. Zinc and magnesium, the potent antagonists of the NMDA receptor complex, are involved in the pathophysiology of depression and exhibit antidepressant activity.

Methods

The present study investigated the potency of Zn²⁺ and Mg²⁺ to [³H] MK-801, which binds to the NMDA receptor channel in the hippocampus of suicide victims (n=17) and sudden death controls (n=6). Moreover, the concentrations of zinc and magnesium (by flame atomic absorption spectrometry) and levels of NMDA subunits (NR2A and NR2B) and PSD-95 protein (by Western blotting) were determined.

Results

Our results revealed that there was a statistically significant decrease (by 29% and 40%) in the potency of zinc and magnesium (respectively) to inhibit [³H] MK-801 binding to NMDA receptors in the hippocampus in suicide tissue relative to the controls. These alterations were associated with increased NR2A (+68%) and decreases in both the NR2B (−46%) and PSD-95 (−35%) levels. Furthermore, lower concentrations (−9%) of magnesium (although not of zinc) were demonstrated in suicide tissue.

Conclusions

Our findings indicate that alterations in the zinc, magnesium and NMDA receptor complex in the hippocampus are potentially involved in the pathophysiology of suicide-related disorders (depression), which may lead to functional NMDA receptor hyperactivity.     

Psychosocial stress, physical symptoms, and anxiety in Greek students

Specific stressor events may be a function of variables such as age, sex, marital status, and urban-rural differences. Psychosocial stress as measured by a Greek adaptation of the Schedule of Recent Experiences was studied in relation to physical symptoms, manifest anxiety, and social desirability in 138 Greek university students. Psychosocial stress was found to be related to physical symptoms and manifest anxiety only in females. The types of stressor events of the students were different from those of a sample of older Greek teachers. The implications of the findings for Greek culture are discussed.     

Psychosocial stress, dietary calcium and hypertension in the spontaneously hypertensive rat

The interactive effects of psychosocial stress and diet on the development of hypertension were investigated in spontaneously hypertensive rats. Psychosocial stress, produced through manipulation of group housing conditions, was evaluated at three levels of dietary calcium and sodium: Low (0.1% Ca2+, 0.25% Na+), Intermediate (1.0% Ca2+, 0.45% Na+), and High (2.0% Ca2+, 1.0% Na+). After 13 weeks of exposure, stressed animals had higher blood pressure and lower serum ionized calcium than nonstressed animals across all diets. Likewise, animals on the low diet had higher blood pressures and lower ionized calcium values than animals on normal or high diets regardless of stress condition. The combination of stress and low diet produced the highest blood pressure and lowest serum ionized calcium values. The results suggest that stress both independently and in combination with dietary Ca2+ altered calcium metabolism. The interaction between psychosocial stress and dietary factors appears to contribute to reductions in serum ionized calcium and elevations in blood pressure in this experimental model of genetic hypertension.     

Psychosocial stress, personality, and the severity of chronic hepatitis C

This cross-sectional study examined the association between the severity of chronic hepatitis C and the type 1 personality, which has been shown by Grossarth-Maticek to be strongly related to the incidence of cancer and mortality. Sixty-nine patients with chronic hepatitis C completed the Stress Inventory, a self-report questionnaire to measure psychosocial stress and personality, and were classified into three groups according to hepatitis severity: group A, chronic hepatitis C with a normal serum alanine aminotransferase level; group B, chronic hepatitis C with an elevated alanine aminotransferase level; and group C, liver cirrhosis. Each of four scales related to the type 1 personality--low sense of control, object dependence of loss, unfulfilled need for acceptance, and altruism--was significantly and positively associated with hepatitis severity. The type 1 score, calculated as the average of these scales, was also strongly related to hepatitis severity (p<0.0001), and adjustment for age, sex, education level, smoking, drinking, and duration brought no attenuation into the association. Chronic psychosocial stress relevant to the type 1 personality may also influence the course of chronic hepatitis C.     

Possible mechanisms of Cyclosporin A ameliorated the ischemic microenvironment and inhibited mitochondria stress in tree shrews’ hippocampus

Objective: The ischemic brain damage is always accompanied by the significant accumulation of glutamate and calcium ions (Ca²⁺). Our objectives were to observe the effects of glutamate and Ca²⁺ overloading in tree shrew's hippocampal microenvironment on mitochondrial stress resulting in cytochrome C release and caspase apoptotic gene activation, and to explore the possible mechanism of Cyclosporin A (CsA) inhibiting mitochondrial stress. Methods: The thrombotic focal cerebral ischemia was induced by photochemical reaction in tree shrews. The extracellular contents of amino acidic neurotransmitters and Ca²⁺ were determined, respectively, with high performance liquid chromatography (HPLC) and atomic absorption spectrophotometry at 4, 24 and 72 h after cerebral ischemia. The glutamate–calcium chloride solutions were microperfused into hippocampus by a kind of single-pumped push–pull perfusion (SPPP) system under three-dimensional orientation instrument in tree shrews. At 24 h, the expression of cytochrome C was observed in perfused lateral hippocampus by immunochemistry. Also, the hippocampus was removed, then mitochondria and cytoplasmic fragment were divided by low temperature centrifugation and the distribution of cytochrome C was assessed through Western blot. Real time fluorescence polymerase chain reaction was used to evaluate the relative amounts of caspase-3 and caspase-9 mRNA. In the treated group, CsA (40 mg/kg) was intravenously injected at 6 h after the microperfuse or cerebral ischemia. The glutamate–calcium solutions were perfused into the hippocampus and inspected the above-mentioned items at 24 h. Data were compared between the two groups (ischemia group vs. sham group, or ischemia group vs. CsA group). Results: Thrombotic cerebral ischemia led to significant increase in extracellular glutamate and Ca²⁺ level of hippocampus (P < 0.01). The cerebral ischemia group and the microperfusion group, which cytochrome C immunoreactivity increased and Western blot analysis demonstrated that the cytochrome C content in the mitochondria of hippocampal cells decreased (P < 0.01), but the cytochrome C in the cytosol increased (P < 0.01). When CsA was intravenously injected at 6 h after the microperfusion or cerebral ischemia, the cytochrome C expression weakened and its release was diminished to a lesser extent. By real time PCR, in relation to the control group, the caspase-3 and caspase-9 mRNA was higher in the glutamate–calcium chloride solution perfused group. CsA treatment cut down the contents of caspase-3 mRNA and caspase-9 mRNA (P < 0.01). Conclusions: It is a primary factor that glutamate and Ca²⁺ accumulate in hippocampal microenvironment, which results in proapoptotic protein cytochrome C release from mitochondria into cytoplasm and caspase cascade activation, and finally mitochondria stress and neuronal secondary injury appear. The neuroprotection of CsA is in relation to inhibiting glutamate receptor overactivation and reducing the Ca²⁺ influx, which can decrease cytochrome C release and caspase mRNA transition.     

单胺类神经元在成年树鼩中枢神经系统中的分布

目的探讨酪氨酸羟化酶(TH)和色氨酸羟化酶2(Tph2)在成年树鼩中枢神经系统(CNS)中的分布特征。方法利用免疫组织化学技术观察TH和Tph2在成年树鼩CNS的分布特征。结果在成年树鼩CNS中,TH阳性信号主要分布于嗅球小球层、纹状体、第3脑室周围区域、未定带、黑质、腹侧被盖区、中央管周围灰质和蓝斑;而成年树鼩CNS中的Tph2阳性信号主要分布于中脑和脑桥中缝复合结构中。结论树鼩TH和Tph2阳性信号的分布模式与脊椎动物的总体分布模式大致相同;某些细节特征显示,树鼩在进化上更接近灵长动物。     

Calretinin immunoreactivity in the prenatally developing olfactory systems of the tree shrew Tupaia belangeri

The prenatal patterns of calretinin immunoreactivity were studied in the olfactory systems of Tupaia belangeri. We investigated the peripheral and primary central parts of the vomeronasal system and of the main olfactory system from the 19th to the 43rd (last) day of gestation and compared the findings with the known calretinin immunoreactivity patterns in adult T. belangeri and the published data on other mammals. The onset of calretinin immunoreactivity was noted in the main olfactory system on the 23rd day of gestation and, in the vomeronasal system, on the 25th day of gestation: single precursors of receptor cells with calretinin immunoreactive perikarya and processes were observed in both epithelia. Their neuronal identity was proven by olfactory marker protein immunoreactivity. On the 42nd day of gestation, almost all receptor cells and nerve fibers, many interneurons and projecting cells were calretinin immunoreactive in the main olfactory and in the vomeronasal systems. In contrast to the intensive calretinin labeling previously observed in virtually all vomeronasal epithelial cells of adult T. belangeri, among developing receptor cells a population of intensively labeled, basally located perikarya was distinguishable from a population of less intensively stained, more apically located ones. In the main olfactory epithelium of fetal T. belangeri, calretinin immunoreactive receptor cells occurred in the middle layers. Whereas in the vomeronasal sensory epithelium differently reacting layers of receptor cells might represent the two known subfamilies of receptor cells, in the main olfactory epithelium the differing calretinin expression in the layers of the epithelium, most probably, did not reflect known subfamilies of odour receptor cells. Transiently, ectopic calretinin immunoreactive receptor cells were observed in the future non-sensory epithelium of the vomeronasal organ.     

Psychosocial stress and treatment outcome following assisted reproductive technology.

This study investigated the association between psychosocial stress and outcome of in-vitro fertilization and gamete intra-Fallopian transfer treatment. Ninety women, enrolled for treatment at a private infertility clinic, completed two self-administered psychometric tests (Bi-polar Profile of Mood States, POMS; and State-Trait Anxiety Inventory, STAI) and a questionnaire to ascertain demographic and lifestyle characteristics before the start of treatment. Approximately 12 months later an outcome measure was determined for each participant in terms of whether she was pregnant or not pregnant and the number of treatment cycles undertaken to achieve clinical pregnancy. The women's scores on the psychological tests were similar to published normative scores. On univariate analysis, history of a previous pregnancy was positively related to the probability of pregnancy and full-time employment, a more 'hostile' mood state and higher trait anxiety were associated with a lower cumulative pregnancy rate. A Cox multiple regression model found previous pregnancy history, trait anxiety, and the POMS agreeable-hostile and elated-depressed scales to be the most important lifestyle and stress variables predictive of pregnancy. The results emphasize the importance of psychosocial stress in treatment outcome but indicate that the relationships are complex. Further studies are required to validate whether these findings can be generalized to other populations.     

Microvascularization of thalamus and metathalamus in common tree shrew (Tupaia glis)

The microangioarchitecture of the thalamus and metathalamus in common tree shrew (Tupaia glis) was studied using vascular corrosion cast/stereomicroscope and SEM technique. The arterial supply of the thalamus and metathalamus was found to originate from perforating branches of the posterior communicating artery, the posterior cerebral artery, the middle cerebral artery, and the anterior choroidal artery. These perforating arteries gave rise to numerous bipinnate arterioles which in turn, with decreasing vessel diameters, branched into a non-fenestrated capillary bed. Venous blood from the superficial parts of the thalamus and metathalamus was collected into the thalamocollicular vein, whereas venous blood from internal aspects of the thalamus was conveyed to the internal cerebral vein. Some venous blood from the most rostral part of the thalamus flowed into tributaries of the middle cerebral vein before draining into the cavernous sinus. Further, the thalamic and metathalamic vascular arrangement was found to be of centripetal type. In addition, thalamic arterial anastomosis was rarely observed. Thus, obstruction of thalamic blood supply could easily lead to thalamic infraction.