The effects of running and meditation on beta-endorphin, corticotropin-releasing hormone and cortisol in plasma, and on mood

The relations between three hormones of the hypothalamic-pituitary-adrenocortical (HPA) axis, beta-endorphin (β-EP), corticotropin-releasing hormone (CRH) and cortisol, and mood change were examined in 11 elite runners and 12 highly trained meditators matched in age, sex, and personality. Despite metabolic differences between running and meditation, we predicted that mood change after these activities would be similar when associated with similar hormonal change. Compared to pre-test and control values, mood was elevated after both activities but not significantly different between the two groups at post-test. There were significant elevations of β-EP and CRH after running and of CRH after meditation, but no significant differences in CRH increases between groups. CRH was correlated with positive mood changes after running and meditation. Cortisol levels were generally high but erratic in both groups. We conclude that positive affect is associated with plasma CRH immunoreactivity which itself is significantly associated with circulating β-EP supporting a role for CRH in the release of β-EP. Increased CRH immunoreactivity following meditation indicates, however, that physical exercise is not an essential requirement for CRH release.     

Human Y-79 retinoblastoma cells express functional corticotropin-releasing hormone receptors

In human Y-79 retinoblastoma cells corticotropin-releasing hormone (CRH) produces a marked and rapid increase of adenylate cyclase activity. The concentration of the peptide producing half-maximal stimulation is 60 nM. The effect of CRH is significantly antagonized by the specific CRH receptor antagonist alpha-helical CHR 9-41 and is mimicked by sauvagine and urotensin I, two peptides displaying sequence homology with CRH. These results demonstrate the presence of functional CRH receptors in human Y-79 retinoblastoma cells and suggest that this cell line may be a suitable model in which to study the action of CRH on human retinal cell function.     

Corticotropin-Releasing Hormone Modulation of a Conditioned Stress Response in the Central Amygdala of Roman High (RHA/Verh)-Avoidance and Low (RLA/Verh)-Avoidance Rats

Roman high (RHA/Verh)- and low (RLA/Verh)-avoidance rats are selected and bred for rapid versus nonacquisition of two-way, active avoidance behavior in the shuttle box. RHA/Verh rats generally show a more active coping style than do their RLA/Verh counterparts when exposed to various environmental challenges. The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine, and behavioral responses to stress. Its involvement in the selection of coping strategies has also been suggested. Corticotropin-releasing hormone (CRH) seems to be one of the key neurohormones in the control of CeA output. Neuroanatomical studies have revealed that the majority of CRH fibers from the CeA have direct connections with autonomic regulatory nuclei in the brain-stem, e.g. lateral parabrachial nucleus (lPB). The effects of CRH (30 ng) on modulating CeA activity were studied by infusion of CRH into the CeA during conditioned stress (inescapable foot-shocks) in RHA/Verh and RLA/Verh male rats. Heart-rate responses after CRH treatment were not changed in either line. However, distinctly different behavioral responses were seen after CRH infusion into the CeA of both rat lines. A decrease in immobility responses was seen in both RHA/Verh and RLA/Verh rats, while an increase in exploration was observed in RHA/Verh rats only in the conditioned stress situation. Rearing levels were increased in the RHA/Verh rats, whereas they were decreased in the RLA/Verh animals. As a result of CRH infusion, the number of FOS immunoreactive cells in the lPB of RLA/Verh rats was decreased, whereas an opposite response was found in RHA/Verh rats. These results indicate that the CRH system of the CeA connected with output brain-stem areas is differentially involved in the cardiovascular and behavioral responses of these rats having different coping styles.     

Changes in brain corticotropin-releasing factor messenger RNA expression in aged Fischer 344 rats

Adaptation in aging may become impaired from abnormal expression of corticotropin-releasing factor (CRF) and altered CRF receptor function. In this study, we measured CRF mRNA levels in Fischer 344 rats at various ages. The brains of these rats were processed for in situ hybridization. Relative to 3-month-old rats, levels of CRF mRNA were significantly decreased in the following brain areas at the following ages: at 24 months in the paraventricular hypothalamus, at 11, 17, and 24 months in the amygdala and at 17 and 24 months in the bed nucleus of the stria terminalis. These changes may contribute to impaired adaptations to stress, cognitive decline and other pathophysiological processes during aging.     

Central leptin suppresses splenic lymphocyte functions through activation of the corticotropin-releasing hormone-sympathetic nervous system

Leptin is one of the key afferent signals that regulate food intake and energy expenditure by acting on specific receptors in the hypothalamus. Recently, leptin was reported to activate the peripheral immune system by acting directly on lymphocytes. To elucidate the brain-mediated participation of leptin in the modulation of peripheral immune functions, we examined the effects of intracerebroventricular (icv) injection of murine recombinant leptin on the proliferative response to Concanavalin A (ConA response) of splenic lymphocytes in rats. The ConA response of splenic lymphocytes was markedly reduced 30 min after icv injection of leptin. The suppressive effect of leptin was abolished completely either by surgical severing of the splenic nerves or by icv injection of an antibody against corticotropin-releasing hormone (CRH), but only partially by an anti-urocortin antibody. Icv injection of CRH and urocortin also suppressed the ConA response of splenic lymphocytes, and the effect of urocortin was prevented by the anti-CRH antibody, while that of CRH was not prevented by the anti-urocortin antibody. These results suggest that leptin suppresses peripheral lymphocyte functions, in contrast to the direct activating effects, indirectly through the activation of the CRH (urocortin)-sympathetic nervous system.     

下丘脑对血糖的调节

下丘脑腹内侧核(VMH)中存在的血糖感受神经元参与全身血糖稳定状态的调节。其中分为两种不同功能的血糖感受神经元:葡萄糖兴奋神经元——当细胞外周环境中葡萄糖浓度升高时能降低其代谢率;葡萄糖抑制神经元——当外周葡萄糖浓度升高时能提高其代谢率。除VMH外,脑中还有更高级的血糖调节中枢,能和VMH部位通过促肾上腺皮质激素释放因子(CRF)、尿皮质醇及促肾上腺皮质激素释放因子受体(CRFRs)相互作用。1型糖尿病患者对低血糖的负调节反应(CRRs)存在缺陷,导致在胰岛素治疗的过程中发生低血糖事件。研究VMH部位对血糖调节的机制能为其治疗提供新的线索。     

尿皮素对体外培养的人脐静脉内皮细胞一氧化氮及一氧化氮合酶的影响

目的:通过检测尿皮素(UCN)对人脐静脉内皮细胞(HUVEC)一氧化氮(NO)生成及一氧化氮合酶(NOS)表达的影响,探讨UCN调节胎儿-胎盘血管张力的分子机制。方法:在离体培养的HUVEC中加入不同浓度的UCN(0、0.1、1、10nmol/L)、10nmol/L促肾上腺皮质激素释放激素(CRH)及向以上各组UCN/CRH同时加α-helical-CRH进行体外培养,用硝酸还原酶法检测细胞上清液中NO的水平,蛋白印迹法检测内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)蛋白表达水平的变化。结果:在与UCN共同培养4~8h后,HUVEC细胞上清液中NO水平呈时间和剂量依赖性变化,随着培养时间的延长,UCN浓度增加,NO水平逐渐升高;UCN组HUVEC iNOS表达水平比对照组明显升高(P<0.05),且呈浓度依赖性升高。而各组eNOS表达水平与对照组比较无明显变化(P>0.05)。UCN/CRH α-helical-CRH组HUVEC上清液中NO水平和HU-VEC iNOS表达水平与对照组比较无明显变化,差异无统计学意义(P>0.05),与相同浓度UCN/CRH组比较NO水平和iNOS蛋白表达水平明显降低,差异有统计学意义(P<0.05)。结论:UCN可促HUVEC合成及释放NO,NO生成增多与UCN通过促进肾上腺皮质激素释放激素2β受体(CRH-R2β)正相调节iNOS蛋白表达有关,这可能是UCN调节胎儿-胎盘血管张力的分子机制之一。     

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.