CHRONIC STIMULATION OF THE HYPOTHALAMUS–PITUITARY–ADRENAL AXIS IN RATS BY INTERLEUKIN 1β: CENTRAL AND PERIPHERAL MECHANISMS

The authors have studied mechanisms which could be involved in the sustained activation of the hypothalamus–pituitary–adrenal (HPA) axis during continuous infusion of rats with recombinant human interleukin-1β (IL-1β). First, the effects of 3 days of intracerebroventricular (i.c.v.) infusion of rats with IL-1 on plasma adrenocorticotropin (ACTH) and corticosterone (B) levels were investigated. Thereafter, changes in plasma ACTH and B levels were followed in rats intraperitoneally (i.p.) infused with IL-1β after immunoneutralization of corticotropin-releasing hormone (CRH), hypophysectomy (HPX), macrophage depletion using dichloromethylene diphosphonate (Cl₂MDP)-containing liposomes, adrenalectomy (ADX) and dexamethasone (DEX) administration, respectively. Infusion of IL-1β i.c.v., even in doses as low as 0.1 μg/day, induced significant increases in plasma ACTH and B levels. HPX and ADX rats died within 18 h after starting the IL-1β infusion (0.5 μg/day). Immunoneutralization of CRH significantly decreased and macrophage depletion significantly increased the stimulation of the HPA axis by IL-1 (4.0 μg/day). Administration of high doses of DEX completely abolished the stimulation of the HPA axis by IL-1β (2.0 μg/day). The present study demonstrates that lower doses of IL-1β were able to activate the HPA axis when infused i.c.v. compared with i.p. Regarding stimulation of the HPA axis by chronic i.p. infusion of IL-1β the present study: (1) provides evidence that the CRH system is involved; (2) provides no evidence for a direct stimulatory effect of IL-1β on the release of B by the adrenal gland which is of sufficient magnitude to resist the stress of chronic i.p. IL-1β infusion; (3) shows that endogenous macrophage-derived mediators, induced by i.p. IL-1β infusion, express an overall inhibitory rather than a stimulatory effect on the activity of the HPA axis; (4) demonstrates that exogenous administration of DEX blocks the effect of IL-1β, which fits well in the concept of an immunoregulatory feedback between IL-1β and glucocorticoids.     

ACTH and glucocorticoid responses under two conditions of stress in macaques

Female macaques were tested under two different psychologically stressful situations in which plasma ACTH and glucocorticoid concentrations were measured. In the first, animals were operantly trained to enter a small transport cage over a four-week period, and plasma ACTH and glucocorticoids were measured in response to brief confinement in the cage before and after training. ACTH values were significantly lower in the pre-test (stress) condition when compared to those for the post-test, whereas the opposite result was found for glucocorticoid values. In the second experiment, blood samples were collected before and one hour after exposure to more acute and severe stress (restraint, venipuncture, handcapture, transport). Both ACTH and glucocorticoid values were significantly elevated from baseline at the post-test sample. The differential relationship between the two hormones among the two experiments was likely the result of the specific timing and magnitude of the stress imposed by each test situation.     

弗洛伊德“人格结构”与麦克林“脑三位一体”学说--《神经美学》教学中遇到的问题、解决方案与讲义

《神经美学》课程在中国科学院大学(国科大)生命科学学院首次开设,吸引了来自生命科学学院内外34种不同专业的99位研究生选课.神经科学或心理学专业的学生占26.5%,虽来自生命科学专业但神经科学知识基础相对薄弱的学生占63.5%,完全没有涉猎过神经科学和心理学的理工科学生占10%.因此,在教学过程中,既要讲授神经科学等方面的基础知识使初学者得以理解《神经美学》,又要时时吸引神经科学和心理学专业研究生的学习兴趣.为此,我们设计了一个有针对性的教学方案,即把《神经美学》专业内容与相关神经科学的基础知识和前沿研究成果匹配在一起讲授,同时注意与学生互动、讨论.比如,在讲授弗洛伊德"人格心理结构"时,先介绍麦克林"脑三位一体"学说和"脑的弥散性调节系统",再讲解"本我"与原始皮层和古皮层、"超我"与新皮层,以及"自我"、"本我"和"超我"的关系.然后讨论艺术创作、审美体验的神经基础,以及对经典画作的理解和审美等.课程内容从人格心理、脑结构、神经元、分子(神经递质)四个层次,为学生构建了一个较为宽广的思维空间.从学生课后提交的学习心得来看,此次教学不仅激发了他们对《神经美学》的兴趣和学习热情,同时提高了学生从美学角度进行思考以及追求美的意识.     

OXR1A,a Coactivator of PRMT5 Regulating Histone Arginine Methylation

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基于脑-肠轴理论探讨针灸治疗认知障碍的机制

认知障碍是一种主要影响认知能力（包括学习、记忆、感知和问题解决等）的心理健康障碍。认知障碍常见于阿尔茨海默病、血管性痴呆、轻度认知障碍等患者。与药物治疗相比，针灸治疗具有低成本、可耐受性和安全等特点，已成为改善认知功能的潜在工具。许多研究表明，在认知障碍的患者中，针灸治疗具有明显改善认知功能的作用。但针灸改善认知功能的机制仍不清楚。基于中医从肠治脑的理论基础以及目前实验研究，脑-肠轴与针灸改善大脑认知功能关系密切。对于针灸改善认知的脑-肠轴机制的理解能促进肠道微生物微观机制研究，但肠道微生物存在个体差异、动态变化、种类繁多等特征，以肠道稳态为调控目标的新针灸方案有待研究完善与规范。本文综述了针灸干预脑-肠轴治疗认知障碍，针灸通过维持肠道生态平衡、保持肠道菌群多样性、调整有益菌群丰度、调节代谢、促进生成脑源性神经营养因子（BDNF）、抑制小胶质细胞激活、降低神经炎症反应、减少Aβ蛋白沉积等机制，实现对认知障碍的治疗。     

Exposure to an Antisense Oligonucleotide Decreases Corticotropin-Releasing Factor Receptor Binding in Rat Pituitary Cultures

Abstract: Corticotropin-releasing factor (CRF) appears to integrate the endocrine, autonomic, immunologic, and behavioral responses of mammals to stress. To investigate further the role of CRF in the CNS, we have begun investigating the usefulness of "antisense knockdown" strategies directed against the CRF receptor using rat anterior pituitary gland primary cell cultures. The 15-mer antisense (5' CTG-CGG-GCG-CCG-TCC 3') and "scrambled" control (5' CGT-CCG-CGC-GCT-GCG 3') oligonucleotides were synthesized based on the rat CRF receptor sequence just downstream of the initiation codon. In each of four separate experiments, exposure to 10 µmol/L of antisense oligonucleotide for 40–67 h resulted in significant (17–36%) decreases in ¹²⁵I-ovine CRF binding to pituitary cells as compared with either control (no oligonucleotide) or 10 µmol/L of "scrambled" oligonucleotide. Moreover, compared with scrambled oligonucleotide, exposure to 10 µmol/L of antisense oligonucleotide, which produced a 22% decrease in CRF receptor binding, also resulted in a significant attenuation of the adrenocorticotrophic hormone response following a 30-min challenge with 100 pmol/L of CRF. Thus, CRF receptor antisense oligonucleotides apparently reduce functional expression of CRF receptors. This technique may be useful in studying the kinetics of CRF receptor production and the physiological functions of CRF receptors within the CNS.     

Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis

We present a general and mathematically rigorous algorithm which allows the helicoidal structure of a protein to be calculated starting from the atomic coordinates of its peptide backbone. This algorithm yields a unique curved axis which quantifies the folding of the backbone and a full set of helicoidal parameters describing the location of each peptide unit. The parameters obtained form a complete and independent set and can therefore be used for analyzing, comparing, or reconstructing protein backbone geometry. This algorithm has been implemented in a computer program named P-Curve. Several examples of its possible applications are discussed.     

A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation

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Discovery of a potent allosteric activator of DGKQ that ameliorates obesity-induced insulin resistance via the sn-1,2-DAG-PKCε signaling axis

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Morphological and architectural features of young Nothofagus pumilio (Poepp. & Endl.) Krasser (Fagaceae)

The morphology and architecture of young Nothofagus pumilio plants growing as understorey and in a cleared area were assessed. Length, number of internodes, presence of branches and apex condition were registered for each growth unit (GU) in the sampled plant. GUs were grouped according to branching order and age of the bearing axis. Understorey plants were seven years old and had a short trunk bearing 2–3 orders of branches; all of their most recent GUs were horizontal and of comparable size. Plants growing in the cleared area were 10–16 years old and had a vigorous vertical and dominant trunk bearing 4–5 orders of less vigorous, horizontal branches. Plants from the cleared area showed signs of having had comparable-size GUs in all of their axes at a younger stage of growth. N. pumilio plants appear to start their growth with the production of short GUs in all of their axes irrespective of the light conditions. In contrast, the development of a vertical, vigorous trunk, seems to be restricted to plants growing in open environments.