Changes in the level of oxygen tension in different brain structures of rats in positive and negative emotional states

Changes of oxygen tension (pO2) level in various brain structures were studied in rats in positive and negative emotional states. It is established that pO2 level changes depend on the character of behavioural reactions: "active" type of behaviour (emotionally positive orienting-investigatory, actively defensive) is accompanied by pO2 level increase, and "passive" type of behaviour ("freezing" reaction)--by a decrease of pO2 level. Changes of oxidative brain metabolism observed at "active" and "passive" types of behaviour indicate, respectively, adaptive and nonadaptive character of these behavioural reactions.     

Effect of substance P on catecholamine levels in the hypothalamus and midbrain in the rat during immobilization stress

Single intraperitoneal injection of substance P in a dose of 125 mcg/kg induced a significant increase of noradrenaline and dopamine level in the hypothalamus and the midbrain of intact rats. Under conditions of immobilization emotional stress, the substance P eliminated the stress induced decrease of hypothalamic noradrenaline and increase of its level in the midbrain; in other words the substance P normalized the noradrenaline level. Modulatory effect of a single injection of the substance P had a long-term character and was synchronized with an earlier found increase of resistability of rats to chronic emotional stress.     

Interrelationship between the neocortex and limbic system in emotional stress and epileptiform syndromes

The paper describes bioelectrical correlates of negative emotional states on three models: 1) states caused by local, chronic electric stimulation of negative emotiogenic zones (in cats, rabbits); 2) by a neurogenic stress in rats resulting from a conflict of afferent excitations; 3) by an experimental syndrome--"expectation stress". The data attest that hypersynchronization of bioelectrical activity in limbic and cortical structures is a sufficiently significant correlate of an emotional stress. It is assumed that hypersynchronization reflects one of the general mechanisms of involvement of brain structures in a state of neurogenic stress and its manifestation.     

Effects of unaccustomed downhill running on muscle damage,oxidative stress,and leukocyte apoptosis

[Purpose]

The purpose of this study was to investigate the effect of unaccustomed downhill running on muscle damage, oxidative stress, and leukocyte apoptosis.

[Methods]

Thirteen moderately trained male subjects performed three 40 min treadmill runs at ~70% VO_2max on separate days: a level run (L) followed by two downhill runs (DH1 and DH2). Blood samples were taken at rest (PRE) and immediately (POST), 2 h, 24 h, and 48 h after each run. Data were analyzed using 2-way repeated measures ANOVA with post hoc Tukey tests.

[Results]

Creatine kinase (CK) activity and oxidative stress level were significantly elevated at 24 h and 48 h following DH1 (P < 0.05). The level of oxidative stress at the POST measurement following DH1 and DH2 was greater than PRE. The rate of leukocyte apoptosis was significantly increased at the POST measurement following all three runs, and remained elevated for up to 48 h following DH1 (P < 0.01).

[Conclusion]

CK activity and oxidative stress were elevated following an acute bout of moderate intensity downhill running, resulting in a greater apoptotic response at 24 h and 48 h post-exercise in comparison with level grade running or a second downhill run. These elevations were blunted following DH2. Although the link between exercise-induced muscle damage and leukocyte apoptosis is currently unknown, the differential response to DH1 vs. L and DH2 indicates that it may be mediated by the elevation of oxidative stress.     

Effects of Caffeine and/OR L-Phenylisopropyladenosine (LPIA) on Local Cerebral Blood Flow and Glucose Utilization in the Rat

Abstract

After LPIA injection, cerebral glucose utilization (LCGU) and blood flow (LCBF) were both decreased. Conversely, caffeine with or without LPIA induced an increase in LCGU and a decrease in LCBF, resetting the ratio of LCBF per unit LCGU at a lower level.     

Dorsal and Ventral Hippocampus Modulate Autonomic Responses but Not Behavioral Consequences Associated to Acute Restraint Stress in Rats

Recent evidence has suggested that the dorsal (DH) and the ventral (VH) poles of the hippocampus are structurally, molecularly and functionally different regions. While the DH is preferentially involved in the modulation of spatial learning and memory, the VH modulates defensive behaviors related to anxiety. Acute restraint is an unavoidable stress situation that evokes marked and sustained autonomic changes, which are characterized by elevated blood pressure (BP), intense heart rate (HR) increases, skeletal muscle vasodilatation and cutaneous vasoconstriction, which are accompanied by a rapid skin temperature drop followed by body temperature increases. In addition to those autonomic responses, animals submitted to restraint also present behavioral changes, such as reduced exploration of the open arms of an elevated plus-maze (EPM), an anxiogenic-like effect. In the present work, we report a comparison between the effects of pharmacological inhibition of DH and VH neurotransmission on autonomic and behavioral responses evoked by acute restraint stress in rats. Bilateral microinjection of the unspecific synaptic blocker cobalt chloride (CoCl_2, 1mM) into the DH or VH attenuated BP and HR responses, as well as the decrease in the skin temperature, elicited by restraint stress exposure. Moreover, DH or VH inhibition before restraint did not change the delayed increased anxiety behavior observed 24 h later in the EPM. The present results demonstrate for the first time that both DH and VH mediate stress-induced autonomic responses to restraint but they are not involved in the modulation of the delayed emotional consequences elicited by such stress.     

The role of cholinergic networks of the anterior basal and inferior frontal lobes in the predatory behaviour of Sepia officinalis

Hyperoxia reduces the hemodynamic latency and enhances the response magnitude of the evoked local cerebral blood flow (LCBF). The objective of this study was to test the hypothesis that a change in the production of nitric oxide (NO) is involved in a unique change in evoked LCBF during hyperoxia. We measured LCBF in alpha-chloralose-anesthetized rats by laser-Doppler flowmetry. Systemic administration of the NO synthase inhibitor N(omega)-nitro-L-arginine (LNA) caused a decline in the baseline level of LCBF (P<0.01). The LNA intravenous injection during hyperoxia (hyperoxia with LNA) reduced the normalized evoked LCBF (normalization with respect to the baseline level of LCBF) in response to somatosensory stimulation by approximately 37% when compared under normal conditions (normoxia without LNA) (P<0.01), although that during normoxia (normoxia with LNA) did not cause a significant difference in the normalized evoked LCBF. The integrated neuronal activity under hyperoxia with LNA was approximately 11% lower than that under normoxia without LNA (P<0.05), although there was no significant difference in integrated neuronal activity between normoxia with LNA and normoxia without LNA. These results do not support our hypothesis and suggest the existence of another interaction mechanism involving oxygen for the enhancement of evoked LCBF under hyperoxia.     

Effects of a chronic stress treatment on vaccinal response in lambs

Farming systems can expose animals to chronic mild stress which is known to induce negative affective state. Affective state in animals, as in humans, can be assessed through behavioral cues. This study aimed to describe the effect of a chronic mild stress, known to induce a negative affective state, on sheep health through their response to vaccination. The study used 15 lambs subjected to a model of chronic mild stress for 15 weeks and 15 lambs reared under conventional farming as a control group. After 7 weeks of stressful treatment, the lambs were individually exposed to a judgment bias test to assess a putative stress-induced ‘pessimism.’ After 15 weeks of stressful treatment, antibody immune response was measured after an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment bias test, revealing a negative affective state. Stressed and control animals showed different immunological reactions to vaccine challenge: stressed sheep had lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase protein concentrations. Antibody response induced by the vaccine strain was not different between stressed and control sheep. Our results suggest that negative affective state induced by chronic stress treatment may induce a stronger inflammatory response to vaccine challenge in sheep. Improvement of animal health may be achieved through consideration of stressors that may affect the emotional and immunological state of sheep.     

Pilot study of inflammatory responses following a negative imaginal focus in persons with chronic pain: Analysis by sex/gender

Background: Recent evidence suggests that differential stress and immune responses may play a role in the sex/gender disparity for pain. Pain pathology and psychological stress are both associated with elevated levels of proinflammatory cytokines.Objective: This pilot study tested a negative imaginal focus to assess whether it would elicit a proinflammatory cytokine response and whether responses would vary by sex/gender.Methods: Adults with chronic musculoskeletal pain were recruited from an outpatient, multidisciplinary pain clinic in Portland, Oregon, between 2007 and 2008. All participants underwent a psychologist-guided 10-minute focus on the negative aspects of their pain condition and the imagined worsening of their pain; no control group was used. Serum collected at baseline and postfocus (1, 2, and 2.5 hours) was assayed for interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Cortisol was assayed at each time point and at 15 minutes postfocus.Results: Thirty-six outpatients (aged 26-62 years; 23 women, 13 men) participated in the study. Compared with men, women displayed greater negative emotional expression during the experiment, and this in turn mediated their IL-6 inflammatory responses. Relative to men, the IL-6 response trajectory was delayed for women. The IL-6 and TNF-a findings suggest women's maximal cytokine responses were not captured by the final time point.Conclusions: This pilot study provides preliminary evidence that women with chronic pain may experience increased and delayed inflammatory responses following negative emotional expression induced by thinking negatively about their pain condition. The findings have implications for pain catastrophizing research. This early-phase research suggests that the timing and duration of the cytokine response are critical factors to consider in future pain research.     

Role of emotional stress in disorders of carbohydrate tolerance

Two series of rabbit experiments were carried out to study the influence of emotional stress on glucose tolerance. Relatively short-term (10 days) chronic emotional stress induced by prolonged (2 h daily) intermittent stimulation of negative emotiogenic zones of the hypothalamus through implanted electrodes led to decreased glucose tolerance. Repeated powerful emotional stresses induced by the clash of food and pain irritation did not pass traceless and manifested in the same glucose tolerance disturbances after a lengthy period of time (1 year).     

Psychophysiological mechanisms of stress in subjects with different representation of activation

The EEG spectral power was calculated in 102 students aged 18-25 years in three experimental conditions (during the common educational process, immediately before and after an examination). Before the examination (stress situation), predominant activation of the right anterior cortical quadrant (the area related with negative emotions, according to R. Davidson, 1993) was revealed by the asymmetry coefficient of the beta rhythm. Subjects with low amplitude of the alpha rhythm (more activated) manifested not only emotional but also autonomic disturbances, while only emotional signs were pronounced in students with high alpha (less activated). Increase in the theta rhythm spectral power during stress and its decrease in the poststress period were observed in the less activated persons, which is considered to be a normal reaction to emotionally negative stimuli. On the contrary, in students with low alpha the theta rhythm power in the stress situation was decreased pointing to their emotional instability. In this group, as distinct from the first one, the beta 2 rhythm recorded in the right anterior cortical quadrant did not decrease in the poststress situation. Together with the observed theta rhythm, decrease in the left-hemisphere and bilateral prefrontal areas in the stress situation, this deviation testifies to a predisposition to the reactive depression of these subjects.     

From Epidemiology to Daily Life: Linking Daily Life Stress Reactivity to Persistence of Psychotic Experiences in a Longitudinal General Population Study

Subclinical psychotic experiences at the level of the general population are common, forming an extended psychosis phenotype with clinical psychosis. Persistence of subclinical experiences is associated with transition to later mental disorder. Increased daily life stress reactivity is considered an endophenotype for psychotic disorders. We examined, in a longitudinal framework, whether baseline momentary assessment markers of stress reactivity would predict persistence of subclinical psychotic experiences over time. In a general population sample of female twins (N = 566), the Experience Sampling Method (ESM; repetitive random sampling of momentary emotions, psychotic experiences and context) was used to assess (emotional and psychotic) daily life stress reactivity. Persistence of subclinical psychotic experiences was based on the Community Assessment of Psychic Experiences (CAPE), assessed three times over 14 months post-baseline. It was investigated whether baseline daily life emotional and psychotic stress reactivity predicted persistence of psychotic experiences over time. Higher levels of emotional stress reactivity (a decrease in positive and an increase in negative affect in response to stress), and increased psychotic reactivity to daily stress was found in individuals with persistent psychotic experiences over time compared to individuals with transient psychotic experiences. The results suggest that markers of daily life stress reactivity may predict “macro-level” persistence of normally transient expression of psychotic liability over time. Linking daily life markers of altered reactivity in terms of emotions and psychotic experiences to longitudinal persistence of psychotic experiences, associated with increased risk of transition to overt mental disorder, may contribute to earlier and more accurate diagnosis of risk.     

Acute and delayed vasoconstriction after subarachnoid hemorrhage: local cerebral blood flow, histopathology, and morphology in the rat basilar artery.

The decreased local cerebral blood flow (LCBF) and cerebral ischemia that occur after subarachnoid hemorrhage (SAH) may be caused by acute and/or delayed vasospasm. In 36 Sprague-Dawley (350-450 g) rats SAH was induced by transclival puncture of the basilar artery. Mean arterial blood pressure (MABP), LCBF, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured in all rats for 30 min before and 60 min after SAH was induced. One set of control (n : 7) and experimental animals (n : 7) was sacrificed after the 60 min of initial post-hemorrhage measurements were recorded. Four days after SAH induction, LCBF and MABP were measured again for 60 min in subgroups of surviving experimental rats (n : 7) and control rats (n : 7). Histopathologic and morphologic examinations of the basilar artery were performed in each subgroup. There was a sharp drop in LCBF just after SAH was induced (55.50 +/- 11.46 mlLD/min/100 g and 16.1 +/- 3.6 mlLD/min/100 g for baseline and post-SAH, respectively; p < 0.001). The flow then gradually increased but had not returned to pre-SAH values by 60 min (p < 0.05). At 4 days after SAH induction, although LCBF was lower than that observed in the control group and pre-SAH values, it was not significantly different from either of these flow rates (p > 0.05). ICP (baseline 7.05 +/- 0.4 mmHg) increased acutely to 75.2 +/- 7.1 mmHg, but returned to normal levels by 60 min after SAH. CPP (baseline 84.5 +/- 6.3 mmHg) dropped accordingly (to 18.6 +/- 3.1 mmHg), and then increased, reaching 72.2 +/- 4.9 mmHg at 60 min after SAH (p > 0.05). Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer in the early stage. LCBF in nonsurviver rats (n : 8) was lower than that in the animals that survived (p < 0.01). At 4 days post-hemorrhage, the rats' basilar arteries showed marked vasculopathy. The findings showed that acute SAH alters LCBF, ICP, and CPP, and that decreased LCBF affects mortality rate. Subsequent vasculopathy occurs in delayed fashion, and this was observed at 4 days after the hemorrhage event.     

Regional Cerebral Glucose Phosphorylation and Blood Flow After Insertion of a Microdialysis Fiber Through the Dorsal Hippocampus in the Rat

Local cerebral glucose metabolism (LCMRglc) and local cerebral blood flow (LCBF) were studied following implantation of a microdialysis fiber in rat dorsal hippocampus. Recovery time after implantation varied from 0 to 24 h. All rats showed pronounced disturbances in LCMRglc and LCBF during the first 2 h of implantation. The changes consisted of (a) a general decrease in blood flow and glucose phosphorylation and (b) small areas (spots) around the fiber with increased glucose phosphorylation and decreased blood flow. Animals allowed to recover for 24 h demonstrated a near normalization of LCMRglu and LCBF, and the focal disturbances (spots) of glucose phosphorylation and blood flow disappeared. The slight reduction in blood flow and glucose metabolism at this time must be accepted, because extension of the recovery period beyond 24 h may give interpretation problems due to the developing gliosis.     

Tetrahydrobiopterin is functionally distinguishable from tetrahydrodictyopterin in Dictyostelium discoideum Ax2

Dictyostelium discoideum Ax2 produces both L-erythro-tetrahydrobiopterin (BH4) and its stereoisomer D-threo-BH4 (DH4). The putative cofactor function of them for phenylalanine hydroxylase (PAH) was investigated through genetic manipulation and quantitative determination of pteridines. In addition to establishing that dihydropteridine reductase (DHPR) and dihydrofolate reductase (DHFR) constitute the regeneration pathway of both BH4 and DH4, the results suggested that BH4 is a preferential cofactor for PAH in vivo, not a secondary product of DH4, which functions mainly as an antioxidant. Our result also demonstrated that PAH may be essential for Dictyostelium growth in nature, and thus it appears that the organism has evolved a strategy to maintain BH4 level via regeneration pathway at the expense of DH4 under oxidative stress conditions.     

玉米ZmSOD基因克隆及其在干旱胁迫下的表达

为探讨超氧化物歧化酶(superoxide dismutase,SOD)基因在玉米抗逆反应中的作用,研究选用2个抗旱性有明显差别的玉米品种为试验材料,采用RT-PCR、实时荧光定量PCR(qRT-PCR)及二维凝胶电泳(2-DE)耦联的基质辅助激光解吸电离/飞行时间质谱(MALDI-TOF)法,对ZmSOD基因的序列结构及其在干旱胁迫下的表达特性进行分析。结果表明：(1)从干旱敏感品种‘登海605’(DH605)和抗旱品种‘蠡玉35’(LY35)玉米叶片中分别成功克隆出ZmSOD1和ZmSOD2基因。DH605中ZmSOD1开放阅读框(ORF)全长456 bp,编码151个氨基酸,编码的蛋白等电点为5.76,分子量为15.05 kD。LY35中ZmSOD2ORF全长459 bp,编码152个氨基酸,编码的蛋白等电点为5.65,分子量为15.11 kD;ZmSOD1和ZmSOD2是亲水性稳定蛋白,都含有Cu/Zn-SOD结构域,蛋白序列N端无信号肽及无跨膜结构域。同源性和系统进化分析表明,玉米ZmSOD和谷子Cu/Zn-SOD2的亲缘关系最近,相似性高达96.05%。(2)在干旱条件下,ZmSOD1在DH605中转录水平明显降低,LY35中ZmSOD2转录水平显著升高;2-DE耦联的质谱分析显示：ZmSOD1在DH605中表达量明显降低,LY35中ZmSOD2表达量无显著性变化,却检测到Mn-SOD蛋白表达量显著增加。(3)相关分析显示,干旱条件下,DH605叶片中ZmSOD1转录水平和其蛋白丰度及SOD酶活性呈极显著性正相关,LY35叶片中ZmSOD2转录水平与SOD酶活性呈显著性正相关。研究结果为进一步探索SOD基因在调节玉米抗性以及逆境胁迫应答过程中的作用机制提供了基础。     

内源性一氧化氮在内毒素引起的肺动脉高压和肺损伤中的作用

本实验观察了家兔静脉内注入内毒素的主要成分脂多糖(LPS)后平均动脉血压(MAP)、肺动脉压(PAP)及入、出肺血NO含量的变化,并观察了静脉内预注入NO生成抑制剂Nω-硝基-L-精氨酸(L-NNA)及诱生型NO生成抑制剂氨基胍(AG)后PAP和肺损伤的变化.结果观察到:家兔LPS注入后,MAP均明显下降,LPS注入后0.5、1、1.5、2h PAP明显增高(P<0.05).LPS注入后PAP的高峰期(1h)入肺血NO含量明显降低,出肺血NO无明显变化.与对照组相比,LPS注入后3h出肺血NO含量和5h入、出肺血NO含量均明显增多.相关分析表明,兔LPS注入前和LPS注入后1h PAP与入肺血NO含量呈明显的负相关,而LPS注入后 3h和5h两者相关不明显.静脉预注入L-NNA后,LPS处理组的动物PAP明显增高,入、出肺血丙二醛(MDA)含量也明显增高,动物生存率明显降低.肺组织光镜下可见肺萎陷和小血管淤血加重,白细胞明显增加.静脉预注入AG后,LPS处理组的动物MAP在3～5h明显增高,此时PAP无明显改变,但5h时血中MDA含量明显减低,5h时与LPS组相比肺萎陷和小血管淤血减轻,白细胞也明显减少.以上结果提示,内毒素入血后较早期阶段可出现PAP的升高,此时入肺血NO的减少是参与肺动脉压增高(PAH)的机制之一.家兔内毒素进入血后较早期阶段NO对减轻内毒素引起的PAH和肺损伤起重要作用,而较晚的时期当诱生型NO合酶(iNOS)诱生后释放的NO则参与内毒素引起的肺组织炎症反应和肺损伤.     

急性恐惧应激对大鼠行为、激素水平及脑Erk1/2活化表达的影响

目的:探讨急性恐惧应激对大鼠情感行为、激素水平及不同脑区Erk1/2活化表达的影响。方法:采用足电击 白噪声刺激方式建立急性恐惧应激大鼠模型,观察其情感行为的改变;放射免疫法及荧光分光光度法检测血浆和脑组织激素水平;Westernblot检测Erk1/2的活化表达。结果:应激后大鼠旷场活动性降低、拒俘反应性增加、惊吓反应增强(P<0.01);血浆及脑组织去甲肾上腺素、5-羟色胺、皮质醇水平增高,而肾上腺髓质素水平降低(P<0.01);海马、纹状体、前额皮质、小脑等脑区磷酸化Erk1/2蛋白的表达均显著增高(P<0.01)。结论:急性恐惧应激可以显著影响大鼠的情感行为和激素水平,Erk1/2蛋白磷酸化水平的增高可能参与了急性恐惧应激所致的情感行为异常。     

Acute and chronic restraint stress alter the incidence of social conflict in male rats

Stress and elevated stress hormone levels are known to alter cognition, learning, memory, and emotional responses. Three weeks of chronic stress or glucocorticoid exposure is reported to alter neuronal morphology in the hippocampus, the amygdala, and the prefrontal cortex, and to decrease neurogenesis in the dentate gyrus. Here we examine the effects of acute and chronic restraint stress exposure on the incidence of emotional responses throughout a 3-week period among adult rat conspecifics. Our data indicate that acute restraint stress (i.e., a single 6-h exposure) results in a significant reduction in aggressive conflicts among stressed males compared to experimental controls. In contrast, on Days 14 and 21, repeatedly restrained rats exhibited significantly more aggressive behaviors than controls. Blood samples taken 18 h after the last restraint session indicate that plasma concentrations of the stress hormone corticosterone (CORT) in stressed rats were equivalent to those of unstressed rats; however, the number of individually initiated aggressive acts observed positively correlated with plasma CORT measures taken at the end of the study. In contrast to studies of psychosocial stress or intruder paradigms, here we observe spontaneous emotional responses to an uncontrollable stressor in the homecage. This study provides a novel examination of the effects of chronic restraint stress on emotional responses in the home environment among cagemates. These results indicate that acute and chronic restraint stress alter the incidence of aggression, and emphasize the relevance of this model of chronic stress to studies of stress-responsive disorders characterized by aggressive behavior.     

Requirement for C-terminal sequences in regulation of Ect2 guanine nucleotide exchange specificity and transformation

Ect2 was identified originally as a transforming protein and a member of the Dbl family of Rho guanine nucleotide exchange factors (GEFs). Like all Dbl family proteins, Ect2 contains a tandem Dbl homology (DH) and pleckstrin homology (PH) domain structure. Previous studies demonstrated that N-terminal deletion of sequences upstream of the DH domain created a constitutively activated, transforming variant of Ect2 (designated DeltaN-Ect2 DH/PH/C), indicating that the N terminus served as a negative regulator of DH domain function in vivo. The role of sequences C-terminal to the DH domain has not been established. Therefore, we assessed the consequences of mutation of C-terminal sequences on Ect2-transforming activity. Surprisingly, in contrast to observations with other Dbl family proteins, we found that mutation of the invariant tryptophan residue in the PH domain did not impair DeltaN-Ect2 DH/PH/C transforming activity. Furthermore, although the sequences C-terminal to the PH domain lack any known functional domains or motifs, deletion of these sequences (DeltaN-Ect2 DH/PH) resulted in a dramatic reduction in transforming activity. Whereas DeltaN-Ect2 caused formation of lamellipodia, DeltaN-Ect2 DH/PH enhanced actin stress fiber formation, suggesting that C-terminal sequences influenced Ect2 Rho GTPase specificity. Consistent with this possibility, we determined that DeltaN-Ect2 DH/PH activated RhoA, but not Rac1 or Cdc42, whereas DeltaN-Ect2 DH/PH/C activated all three Rho GTPases in vivo. Taken together, these observations suggest that regions of Ect2 C-terminal to the DH domain alter the profile of Rho GTPases activated in vivo and consequently may contribute to the enhanced transforming activity of DeltaN-Ect2 DH/PH/C.