下丘脑Kiss1神经元在能量代谢调节中的作用

代谢是机体生存和延续的基础,机体通过影响行为并诱发一系列的生理反应,调节代谢状态。能量代谢失衡可能导致机体消瘦或肥胖,甚至会造成生长发育和生殖功能的障碍等。因此,维持机体的能量平衡至关重要,而这一状态的维持受中枢神经系统的严格控制。中枢神经系统,特别是下丘脑,在调节机体生理功能和能量平衡中发挥着重要的作用。下丘脑Kisspeptin被认为在调节性腺轴、营养性发育和生殖中发挥重要作用。近些年来,关于其在能量代谢调控中的作用也引起广泛关注。本文将从能量摄入和能量消耗两个方面对下丘脑Kisspeptin在能量代谢调控中的作用进行综述,以期为防治因能量失衡诱发的代谢性疾病提供新的研究思路和依据。     

综述与专论:乳酸代谢/乳酰化在运动改善中枢神经系统疾病中的作用及机制

中枢神经系统疾病是全球致残的主要原因及第二大死亡原因,其病理机制复杂,严重影响患者身心健康与生活质量。深入探讨防治中枢神经系统疾病的潜在靶点及靶向明确的干预手段具有重要意义。乳酸作为糖酵解的核心代谢产物,可通过乳酸代谢及乳酰化调节β淀粉样蛋白沉积、Tau蛋白磷酸化、神经炎症、内皮细胞凋亡、神经元铁死亡、小胶质细胞增殖及肿瘤细胞免疫逃逸等病理机制,参与中枢神经系统疾病的发生发展。研究证实,运动可通过调控乳酸代谢及乳酰化,在中枢神经系统疾病中发挥保护效应。本文综述乳酸代谢及乳酰化在中枢神经系统疾病中的作用,以及运动调控乳酸代谢及乳酰化改善中枢神经系统疾病的潜在作用机制,为运动裨益脑健康提供理论依据。     

感染在神经退行性疾病中的调控机制

神经退行性疾病以突触丢失和神经元死亡为特征,表现为认知功能下降、痴呆和运动功能丧失.流行病学和实验证据提示:慢性细菌、病毒和真菌感染可能是导致神经退行性疾病如阿尔兹海默症(AD)、帕金森病(PD)、肌萎缩性侧索硬化症(ALS)和多发性硬化症(MS)等的危险因素.病原体在中枢神经系统的持续感染可导致一系列细胞生物学功能的...     

氨基酸代谢与肝性脑病

肝性脑病 (HepaticEncephalopathy)又称肝昏迷 ,即由于严重肝病引起的中枢神经系统功能紊乱 ,患者出现一系列神经精神病状 ,直至进入昏迷。在此仅从氨基酸代谢异常的角度叙述与肝性脑病的关系。     

Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators

Glutamate in excessive amounts is a major contributor to neuronal degeneration, and its removal is attributed mainly to astrocytes. Traumatic injury to the central nervous system (CNS) is often accompanied by disappearance of astrocytes from the lesion site and failure of the remaining cells to withstand the ensuing toxicity. Microglia that repopulate the lesion site are the usual suspects for causing redox imbalance and inflammation and thus further exacerbating the neurotoxicity. However, our group recently demonstrated that early post-injury activation of microglia as antigen-presenting cells correlates with an ability to withstand injurious conditions. Moreover, we found that T cells reactive to CNS-specific self-antigens protected neurons against glutamate toxicity. Here, we show that antigen-specific autoimmune T cells, by tailoring the microglial phenotype, can increase the ability of microglia-enriched cultures to remove glutamate. This T-cell-mediated effect could not be achieved by the potent microglia-activating agent lipopolysaccharide (LPS), but was dose-dependently reproduced by the Th1 cytokine interferon (IFN)-gamma and significantly reduced by neutralizing anti-IFN-gamma antibodies. Under the same conditions, IFN-gamma had no effect on cultured astrocytes. Up-regulation of glutamate uptake induced by IFN-gamma activation was not accompanied by the acute inflammatory response seen in LPS-activated cultures. These findings suggest that T cells or their cytokines can cause microglia to adopt a phenotype that facilitates rather than impairs glutamate clearance, possibly contributing to restoration of homeostasis.     

Ontogeny of the collar cord: Neurulation in the hemichordate Saccoglossus kowalevskii

The chordate body plan is characterized by a central notochord, a pharynx perforated by gill pores, and a dorsal central nervous system. Despite progress in recent years, the evolutionary origin of each of theses characters remains controversial. In the case of the nervous system, two contradictory hypotheses exist. In the first, the chordate nervous system is derived directly from a diffuse nerve net; whereas, the second proposes that a centralized nervous system is found in hemichordates and, therefore, predates chordate evolution. Here, we document the ontogeny of the collar cord of the enteropneust Saccoglossus kowalevskii using transmission electron microscopy and 3D‐reconstruction based on completely serially sectioned stages. We demonstrate that the collar cord develops from a middorsal neural plate that is closed in a posterior to anterior direction. Transversely oriented ependymal cells possessing myofilaments mediate this morphogenetic process and surround the remnants of the neural canal in juveniles. A mid‐dorsal glandular complex is present in the collar. The collar cord in juveniles is clearly separated into a dorsal saddle‐like region of somata and a ventral neuropil. We characterize two cell types in the somata region, giant neurons and ependymal cells. Giant neurons connect via a peculiar cell junction that seems to function in intercellular communication. Synaptic junctions containing different vesicle types are present in the neuropil. These findings support the hypotheses that the collar cord constitutes a centralized element of the nervous system and that the morphogenetic process in the ontogeny of the collar cord is homologous to neurulation in chordates. Moreover, we suggest that these similarities are indicative of a close phylogenetic relationship between enteropneusts and chordates. J. Morphol., 2010. ©2010 Wiley‐Liss, Inc.     

Mono-ADP-Ribosylation in Brain: Purification and Characterization of ADP-Ribosyltransferases Affecting Actin from Rat Brain

Four ADP-ribosyltransferases that acted on non-muscle actin were purified more than 3,000-fold from rat brain extract. The molecular weights of these brain ADP-ribosyltransferases were 66,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration on TSK gel G3000SW. The Km values for NAD were approximately 20 microM. These enzymes were not inhibited by thymidine or nicotinamide, but were inhibited by ADP and ADP-ribose. Two soluble ADP-ribosylation factors purified from rat brain had different effects on the four ADP-ribosyltransferases during the ADP-ribosylation of non-muscle actin. These ADP-ribosyltransferases modified not only actin but also the stimulatory guanine nucleotide-binding protein of adenylate cyclase, Gs, and another guanine nucleotide-binding protein in brain, Go. These findings suggest that the four brain ADP-ribosyltransferases are concerned with nerve functions in the central nervous system.     

Organization of the orthogon – main and minor nerve cords

The central nervous system of flatworms has been regarded as comprised of the bilobed brain, the longitudinal cords and the connecting transverse commissures forming a so called orthogon. The peripheral nervous system comprises the submuscular and subepidermal plexuses. As a confusion in the terminology of the longitudinal nerve cords has prevailed, two concepts have been introduced, the main nerve cords (MCs) and the minor cords. The MCs have been defined as the pair of longitudinal nerve cords that (1) start with strongest roots in the brain, (2) consist of wide fibre bundles and (3) are associated with more neurons (particularly amninergic marker neurons) than the other cords. Longitudinal nerve cords in other positions are thinner and have less pronounced contact with the brain. They have collectively been named minor cords. Support for the special status of the MCs has been obtained from studies of the neuroanatomy of Catenulida, Macrostomida, Proseriata, Tricladida and Lecithoepitheliata and of parasitic flatworms. Using the above mentioned criteria for the MCs and the results of recent studies, we present the following hypothese: The MCs in all flatworms correspond to each other and have a common origin. This revised version was published online in July 2006 with corrections to the Cover Date.     

Age-associated changes in central nervous system glycerolipid composition and metabolism

In this review, changes in brain lipid composition and metabolism due to aging are outlined. The most striking changes in cerebral cortex and cerebellum lipid composition involve an increase in acidic phospholipid synthesis. The most important changes with respect to fatty acyl composition involve a decreased content in polyunsaturated fatty acids (20:4n-6, 22:4n-6, 22:6n-3) and an increased content in monounsaturated fatty acids (18:1n-9 and 20:1n-9), mainly in ethanolamine and serineglycerophospholipids. Changes in the activity of the enzymes modifying the phospholipid headgroup occur during aging. Serine incorporation into phosphatidylserine through base-exchange reactions and phosphatidylcholine synthesis through phosphatidylethanolamine methylation increases in the aged brain. Phosphatidate phosphohydrolase and phospholipase D activities are also altered in the aged brain thus producing changes in the lipid second messengers diacylglycerol and phosphatidic acid.     

Evidence that endogenous thyrotropin-releasing hormone (TRH) may control vagal efferents to thyroid gland: neural inhibition by central administration of TRH antiserum

The intracerebroventricular (i.c.v.) injection of rabbit antiserum to thyrotropin-releasing hormone (TRH) to the urethane anesthetized rat inhibited the spontaneous electrical discharge of the superior laryngeal nerve (n.sl). On the other hand, the i.c.v. injection of rabbit antiserum to somatostatin (SRIF) failed to influence the nerve activity whereas SRIF itself is capable of inhibiting the n.sl activity. These findings suggest that TRH in the brain takes a role continuously in regulating the neural activity while SRIF is involved in the neuronal circuits as an agent for the down regulation of the autonomic nervous system.     

New era of optogenetics: from the central to peripheral nervous system

Abstract

Optogenetics has recently gained recognition as a biological technique to control the activity of cells using light stimulation. Many studies have applied optogenetics to cell lines in the central nervous system because it has the potential to elucidate neural circuits, treat neurological diseases and promote nerve regeneration. There have been fewer studies on the application of optogenetics in the peripheral nervous system. This review introduces the basic principles and approaches of optogenetics and summarizes the physiology and mechanism of opsins and how the technology enables bidirectional control of unique cell lines with superior spatial and temporal accuracy. Further, this review explores and discusses the therapeutic potential for the development of optogenetics and its capacity to revolutionize treatment for refractory epilepsy, depression, pain, and other nervous system disorders, with a focus on neural regeneration, especially in the peripheral nervous system. Additionally, this review synthesizes the latest preclinical research on optogenetic stimulation, including studies on non-human primates, summarizes the challenges, and highlights future perspectives. The potential of optogenetic stimulation to optimize therapy for peripheral nerve injuries (PNIs) is also highlighted. Optogenetic technology has already generated exciting, preliminary evidence, supporting its role in applications to several neurological diseases, including PNIs.     

Metabolism and Distribution of Guanosine Given Intraperitoneally: Implications for Spinal Cord Injury

Intraperitoneal administration of guanosine to rats with chronic spinal cord injury stimulates remyelination and functional recovery. If guanosine produced its effects in the nervous system, it should enter it and elevate endogenous concentrations. [ ³ H]-guanosine (8 mg/kg) was administered intraperitoneally to rats and its distribution and concentration in different sites determined. Guanosine rapidly entered all tissues; its concentration peaked at about 15 minutes except in adipose tissue and CNS where it continued to rise for 30 minutes. Its chief metabolic product in all sites was guanine with over twice as much guanine as guanosine present in CNS after 30 minutes.