脑源性神经营养因子的研究进展

近年来,科学研究发现神经营养因子是参与调控神经系统多种生理功能的一种蛋白质。其中,脑源性神经营养因子是一种在脑内合成的小分子二聚体蛋白质,对中枢系统神经元的生长、发育、分化、再生和修复具有重要作用。本文对脑源性神经营养因子的结构、功能、疾病相关性及临床应用前景进行了综述。     

脑源性神经营养因子:治疗阿尔采末病的新策略

阿尔采末病(又名阿尔茨海默病)的病因及发病机制复杂不清,目前脑源性神经营养因子在其发生、发展过程中的作用日益受到关注。本文综述了脑源性神经营养因子的生物学特点及作用,特别强调了脑源性神经营养因子在阿尔采术病病理生理学过程中的作用,旨在为后续研究该病的治疗药物提供新策略。     

首发抑郁症患者血清NGF及NT-3水平的研究

抑郁症是一种常见的危害人类情感及健康的精神疾病,其发病率呈逐年增高的趋势［1］。目前为止,抑郁症的病因及发病机制尚不明确。脑源性神经营养因子、神经生长因子、神经营养素3等都属于神经营养素的蛋白质生长因子家族。神经生长因子（NGF）与神经营养因子3（NT‐3）是由星型胶质细胞合成和分泌的具有维持神经元的存活、损伤修复等生物学作用。     

脑源性神经营养因子对离子通道的调节作用

脑源性神经营养因子（brain derived neurotrophic factor,BDNF）是神经营养因子（neurotrophicfactors,NTF）家族成员之一,对中枢和周围神经系统多种神经元的生长、发育、分化、维持和损伤修复起重要作用。BDNF还能够调节神经元静息膜电位、神经兴奋性和突触传递,在突触可塑性过程中起重要作用,这些作用与其对离子通道的调节有关。BDNF不仅可以与TrkB受体结合激活第二信使级联反应和蛋白磷酸化过程调节离子通道的性质,还可以直接调节钠通道活性。可见,BDNF还具有神经调质和兴奋性递质的作用。     

红景天苷与脑源性神经营养因子联合对NSCs定向分化及对癫痫影响

癫痫是神经系统中仅次于脑血管病的第二大疾病,我国约600多万患者,其中25%为难治性癫痫,目前主要有药物和外科治疗两种手段,其效果均不理想。现今神经干细胞移植治疗癫痫已是研究热点。本实验通过观察红景天苷、脑源性神经营养因子(BDNF)联合对体外海马神经干细胞     

脑源性神经营养因子在实验性糖尿病及其并发症中的表达及研究

脑源性神经营养因子（BDNF）属于一类神经营养因子,与对应受体TrkB相结合充分发挥有效生理作用能够促进神经系统发育、分化、生长,并促使神经元保持正常生理功能,与糖尿病存在较为密切相关性。本文分析BDNF与糖尿病及并发症相关性进行综述研究。     

精神分裂症与C270T基因多态性研究进展

精神分裂症是在遗传和神经发育缺陷基础上产生,疾病发展的最初几年往往是部分脑区萎缩最快的时期.近年来,伴随着神经影像学、神经生物化学、分子生物学和神经电生理学等研究方法的快速发展与应用,人们的注意焦点已从受体转移到基因翻译因子和基因表达的变化上,基因研究和神经环路分析的两大技术整合,为揭示精神分裂症生物学病因指明方向.其中,神经营养因子系统,特别是脑源性神经营养因子（BDNF,brain-derived neurotrophic factor）的启动子C270T基因多态性与精神分裂症的关联性研究,得到国内外学者越来越多的关注.目前已经发现BDNF和多种疾病的发病和治疗存在相关性,如精神分裂症、阿尔茨海默病、抑郁症、帕金森病、脑缺血性疾病、多发性硬化、视网膜神经病变和糖尿病性末梢神经病变等.本文介绍脑源性神经营养因子C270T的基因多态性和精神分裂症的最新研究进展.     

脑源性神经营养因子与抑郁症

脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)是神经营养家族中的重要成员。BDNF可促进神经系统的发育,维持神经系统的功能,在各种神经的生长发育以及再生中起重要作用。近年来的研究表明,BDNF在抑郁症及其并发症的诊治中发挥重要作用。该文综述了BDNF、BDNF受体和信号转导通路在抑郁症以及糖尿病、脑卒中、产后、慢性疼痛等并发抑郁症中的研究现状。     

ZW1-2对局灶脑缺血小鼠纹状体、皮质及海马脑区BDNF和VEGF蛋白表达的影响

目的观察化合物zome wermel 1-2(ZW1-2)对小鼠永久性局灶脑缺血后的神经功能,以及对脑源性营养因子和血管内皮生长因子的影响。方法制备小鼠永久性局灶脑缺血模型,并分别于脑缺血后2.5 h和7.5 h,灌胃给予不同剂量的化合物ZW1-2,脑缺血后24 h采用免疫组化法测定小鼠各个脑缺血易损区的脑源性神经营养因子和血管内皮生长因子表达情况。结果 ZW1-2能够显著降低小鼠局灶性脑缺血导致的行为功能评分,可以显著提高皮质、纹状体和海马脑区的脑源性神经营养因子表达,显著降低这些脑区中的血管内皮生长因子蛋白表达。结论 ZW1-2具有抗实验性脑缺血作用,其作用机制可能通过调控脑源性神经营养因子以及血管内皮生长因子而起到对脑缺血损伤的治疗作用。     

脑源性神经营养因子与脑卒中后疼痛和抑郁的关系

脑源性神经营养因子（BDNF）是成人脑内含量最丰富的神经营养因子,具有显著的脑损伤修复能力。最近的多项研究表明,BNDF在脑卒中后的多种并发症的发生发展中起到了重要的作用,有希望成为新的卒中治疗方法的晚期靶点,但它的作用机制尚不明确。本文就BDNF的生物学特性、在卒中后并发症的作用机制以及最新的研究进展进行综述,从而为...     

脑源性神经营养因子在抑郁症中的研究进展

脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）是参与机体情绪和认知功能至关重要的调节因子，能够促进脑内神经发生和突触发育。在抑郁患者及抑郁动物模型中，BDNF前体（brain-derived neurotrophic factor precursor，proBDNF）和前肽水平升高，BDNF成熟体（mature brain-derived neurotrophic factor，mBDNF）水平降低；抗抑郁药物治疗后，能够抑制proBDNF以及BDNF前肽的表达，促进mBDNF/proBDNF蛋白比值的升高。目前临床常见抗抑郁药的抗抑郁作用多依赖于BDNF及相关蛋白的信号转导。本文通过查阅文献，对BDNF及其相关因子在抑郁症中的作用进行总结。     

一氧化氮合酶抑制剂的研究进展

一氧化氮（ｎｉｔｒｉｃｏｘｉｄｅ,ＮＯ）是一种能调节细胞多种功能的信息分子,它参与心血管、外周和中枢神经以及免疫等系统生理过程和生物信号的调节。体内组织中的ＮＯ由ＮＯ合酶（Ｎｉｔｒｉｃｏｘｉｄｅｓｙｎｔｈａｓｅ,ＮＯＳ）催化左旋精氨酸而合成,合成后的ＮＯ迅速跨膜扩散释放。各种调节ＮＯ释放的因素均作用于ＮＯＳ催化的化学反应过程,而体内影响该反应的ＮＯＳ在各组织的表达不同。特异性ＮＯＳ抑制剂通过调控ＮＯ的合成,对ＮＯＳ表达相关的各种疾病的预防和治疗具有重要的临床意义。本文对近年来ＮＯＳ抑制剂的研究进展作一概述。     

Functions of connexin-43 in neural development and its relationship with neural diseases

Connexin43(Cx43) is a kind of gap junction protein, which not only is expressed in astrocytes,but also in excitatory neurons of development stage. As we know, neurons and glial cells are vital parts in the brain, making contribution to function wel of central nervous system. Dysplastic astrocytes and neurons give rise to the occurrence of almost all neural diseases. Accruing evidence has indicated that Cx43 plays crucial roles in synaptic formation and transmission by the function and development of hemichannels in astrocytes. However,the exact roles of Cx43 in excitatory neurons of developmental stage and neural diseases are not very clear. In this review, we first describe the expression pattern of Cx43 in developmental central nervous system. Then,we address the roles of Cx43 in astrocytes. Further, the function of Cx43 in excitatory neurons are presented.Last, we summarize the dominating mechanisms of Cx43 involved in the onset and progress of neural diseases,especially neurodegenerative disease. Clearly, the investigations on the functions of Cx43 in the progress of neural diseases will benefit not only the new understanding of pathogenesis, but also potential therapeutic targets to ameliorate the states of related neural diseases.     

Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats

Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1?mg/mL drinking solution for 30?days) on short- and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats. Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels. In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age. These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding. This article is part of a Special Issue entitled 'Cognitive Enhancers'.     

Endothelin and the central and peripheral nervous systems: a decade of endothelin research

1. During the past decade, extensive investigation of the endothelin (ET) system, primarily characterized by its potent vasoactive peptide element ET-1, has suggested a prominent role for this humoral agent and its isopeptides in cardiovascular and neural regulation. 2. Major elements of this system, including its peptide isoforms, converting enzymes involved in their formation and metabolism, as well as multiple receptor subtypes, have been localized within various components of the cardiovascular system and the central and peripheral nervous systems. 3. An understanding of the possible roles for the ET system in neural regulation and development has progressed over the past several years; most notable is the influence of ET on the central control of cardiovascular function and sympathetic tone. 4. The present concentrated review of ET and the central and peripheral nervous systems is presented to introduce the other papers within this symposium by briefly describing the presence and influence of components of this unique peptide system within pertinent physiological structures involved in cardiovascular, adrenal, sympathetic and enteric developmental function.     

Physiological roles of neurite outgrowth inhibitors in myelinated axons of the central nervous system--implications for the therapeutic neutralization of neurite outgrowth inhibitors

It has long been recognized that the central nervous system (CNS) exhibits only limited capacity for axonal regeneration following injury. It has been proposed that myelin-associated inhibitory molecules are responsible for the nonpermissive nature of the CNS environment to axonal regeneration. Experimental strategies to enhance regeneration by neutralizing these inhibitory molecules are rapidly advancing toward clinical application. It is therefore important that the physiological distribution and functions of these supposed inhibitory molecules should be understood. In this review, we examine the distribution of these inhibitors of neurite outgrowth in relation to the longitudinal polarization of the myelinated axon into the node of Ranvier and associated domains and explore their potential domain specific physiological functions. Potential implications for the therapeutic strategy of neutralizing these inhibitory molecules to promote neural repair are discussed.     

Molecular pharmacology and therapeutic prospects of metabotropic glutamate receptor allosteric modulators

The metabotropic glutamate receptors (mGluR) consist of a family of eight G-protein-coupled receptors that differ in their function, distribution and physiological roles within the central nervous system. In recent years substantial efforts have been made towards developing selective agonists and antagonists which have proven useful for elucidating their potential as novel targets for the treatment of psychiatric and neurological diseases. In the present review we will provide an update of the recent developments of functional allosteric modulators of the mGluR family and explore their therapeutic potential for anxiety/depression, schizophrenia, epilepsy/stroke, pain and Alzheimer's, Parkinson's and Huntington's diseases.     

Brain neuronal nicotinic receptors as new targets for drug discovery

Neuronal nicotinic receptors (nAChRs) are a heterogeneous family of ion channels differently expressed in the nervous system where, by responding to the endogenous neurotransmitter acetylcholine, they contribute to a wide range of brain activities and influence a number of physiological functions. Over recent years, the application of newly developed molecular and cellular biological techniques has made it possible to correlate the subunit composition of nAChRs with specific nicotine-elicited behaviours, and refine some of the in vivo physiological functions of nAChR subtypes. The major new findings are the widespread expression of nAChRs, outside the nervous system, their specific and complex organisation, and their relevance to normal brain function. Moreover, the combination of clinical and basic research has better defined the involvement of nAChRs in a growing number of nervous pathologies other than degenerative diseases. However, there are still only a limited number of nicotinic-specific drugs and, although some nicotinic agonists have an interesting pharmacology, their clinical use is limited by undesirable side effects. Some selective nicotinic ligands have recently been developed and used to explore the complexity of nAChR subtype structure and function in the expectation that they will become rational therapeutic alternatives in a number of neurodegenerative, neuropsychiatric and neurological disorders. In this review, we will discuss the molecular basis of brain nAChR structural and functional diversity mainly in pharmacological and biochemical terms, and summarise current knowledge concerning the newly discovered drugs used to classify the numerous receptor subtypes and treat the brain diseases in which nAChRs are involved.     

Male infertility: A proximate look at the advanced glycation end products

Advanced glycation end products (AGEs) are products of cascades of non-enzymatic glycosylation. They are formed over a period of hours to days, depending on the protein lifetime. AGEs acts by independently producing reactive oxygen species (ROS) or by binding to their receptors. Binding of AGE to the receptor for advanced glycation end products (RAGE) has been shown to play a role in physiological processes, including lung homeostasis, bone metabolism, neuronal systems and the immune system. When in excess, they take part in the pathogenesis of diseases such as diabetes mellitus, cardiovascular diseases, neurodegenerative diseases, and etcetera.The cause of male infertility is considered unexplained in many cases, suggesting that there are gaps in the mechanistic knowledge of sperm production and function, especially, pathways involved in the physiochemical protein regulation of spermatogenesis. It is therefore important to consider areas of research highlighting protein modification and identification and their implication for male fertility.