动物进化中神经肽样物质和神经系统关系之探讨

用免疫组织化学方法,研究和追踪神经肽样物质在原生动物、水螅及蝾螈胚胎发育过程中分布的变化,试图探索在动物早期进化过程中神经肽样物质和神经系统之间的关系。实验结果表明：（1）从系统发育看神经肽样物质比神经系统先出现并行使在细胞内的功能。（2）在随后的进化中神经肽样物质先分布于非神经系统部位,如肠道外缘及表皮,并逐渐进入神经系统,这无论从系统发育和个体发育中都能找到依据。（3）在神经系统,神经肽样物质先出现在周边神经,之后;才出现在中枢神经,实验中表明NPY是随着神经嵴细胞的迁移而进入周边神经系统,之后,随着胶质细胞的出现而出现在中枢神经系统。（4）原生动物和蝾螈胚胎均由皮膜或表皮细胞中囊泡状结构直接分泌神经肽祥物质进入胞质内或细胞外。     

神经肽Y和β-内啡肽样免疫阳性物质在文昌鱼神经系统和哈氏窝的分布

用免疫组织化学方法首次发现,神经肽Y(NPY)和β-内啡肽(β-Ep)样免疫阳性物质分布在文昌鱼神经系统和哈氏窝。NPY样免疫阳性神经元出现在端脑前部和中部、中脑前部和中部以及后脑,NPY样免疫阳性神经纤维在文昌鱼脑的各部分与神经元交错呈网状密集分布。神经管的背面与中部均可观察到NPY样免疫阳性神经元及其阳性纤维。β-Ep样免疫阳性神经元及其神经纤维定位在中脑前部和中部以及神经管,且分布范围明显小于NPY。文昌鱼哈氏窝也有NPY和β-Ep样免疫阳性物质分布。这些结果表明,NPY和β-Ep可能作为脑内的一种神经递质,像鱼类那样,参与调节文昌鱼哈氏窝促性腺激素分泌细胞的分泌活动,这为文昌鱼脑-哈氏窝复合体的密切关系提供新的形态学证据。     

神经肽Y和β—内啡肽样免疫阳性物质在文昌鱼神经系统和哈氏窝的分布

用免疫组织化学方法首次发现,神经肽Y（NPY）和β－内啡肽（β－Ep)样免疫阳性物质分布在文昌鱼神经系统和哈氏窝。NPY样免疫阳性神经元出现在端脑前部和中部、中脑前部和中部以及后脑,NPY样免疫阳性神经纤维在文昌鱼脑的各部分与神经元交错呈网状密集分布。神经管的背面与中部均可观察到NPY样免疫阳性神经元及其阳性性纤维。β－Ep样免疫阳性神经元及其神经纤维定位在中脑前部和中部以及神经管,且分布范围明显小于NPY。文昌鱼哈氏窝也有NPY和β－Ep样免疫阳性物质分布。这些结果表明,NPY和β－Ep可能作为脑内的一种神经递质,像鱼类那样,参与调节文昌鱼哈氏窝促性腺激素分泌细胞的分泌活动,这为文昌鱼脑－哈氏窝复合体的密切关系提供新的形态学证据。     

谷氨酸转运体GLT-1的剪接变异体研究进展

随着对谷氨酸转运体1(glial glutamate transporter 1, GLT-1)研究的深入,发现GLT-1存在多种剪接变异体.这些变异体除在中枢神经系统大量分布外,在受试动物的其它部位也有分布.中枢神经系统内的GLT-1剪接变异体在星形胶质细胞和神经元上均有表达,且这些剪接变异体在中枢神经系统的分布还呈现出区域定位及亚细胞定位不均衡的特性.     

新生鼠中枢神经系统内Nestin蛋白免疫阳性的组织分布

为了观察Nestin在新生SD大鼠中枢神经系统中的分布,探讨神经干细胞在新生鼠的分布.采用免疫荧光法,显示含神经干细胞特征性的标志物Nestin的阳性结构在新生SD大鼠中枢神经系统中的分布.结果表明在新生SD大鼠中枢神经系统中,Nestin在前脑、脑干和小脑的各个部位均有表达,阳性结构多为纤细的纤维状突起,分布密集,标记强度多为中等强度,分布相对比较均匀.在脊髓实质的Nestin免疫阳性产物明显减少,分布稀疏,染色也较浅,中央管Nestin免疫染色阳性的室管膜细胞很少,但在脊髓中央管的背侧(延髓见于腹侧和背侧)可见到“喷泉”状免疫强阳性纤维束垂直伸展,直达软膜.由此可得出结论:新生SD大鼠中枢神经系统的广泛脑区均存在大量的神经干细胞,而脊髓的神经干细胞数目较少,提示神经干细胞在生后从神经系统的尾端开始逐渐减少.     

中枢神经系统中的胃泌素释放肽：在厌恶性情绪记忆中的作用及机制研究

胃泌素释放肽(gastrin-releasing peptide,GRP)是蛙皮素(bombesin,BB/BN)在哺乳动物中的同系物,在中枢神经系统中广泛分布,是一种重要的脑内神经调质,参与动物的多种生理功能和本能行为,在大脑的高级功能方面也发挥一定的作用.在神经系统中,随着GRP水平的改变,动物的记忆特别是与恐惧、焦虑相关记忆的形成、巩固和消退以及突触可塑性均发生不同程度的变化.GRP及其受体还被认为与神经系统性疾病有关,是潜在的神经系统性疾病的治疗靶点,但其相关的机制尚未明确.很多研究者基于不同实验方法提出了相关假设.本文从传统药理学、遗传学和电生理学方面对GRP系统在厌恶性情绪驱动的记忆、突触可塑性变化以及在中枢神经系统中的作用机制进行综述,希望为进一步明确GRP系统在中枢神经系统中的作用研究提供新的思路.     

猫视网膜多巴胺能无长突细胞发育的中央—周边梯度

本文报道用酪氨酸羟化酶(TH)免疫细胞化学方法标记猫视网膜多巴胺(DA)能无长突细胞发育的中央—周边梯度。TH阳性反应的I型DA能无长突细胞在发育成熟过程中呈现时空顺序的中央—周边梯度:(1)P_1时期分化较高的细胞,即染色深,胞体大,具有2—4支树突,分枝分布于内网状层(IPL),最外缘的星状Ⅰ_1类细胞大都集中于视网膜的中央部位;而分化较低的细胞,即染色淡,胞体小,具有1—2支树突,分枝分布于IPL外层和中层的不规则形Ⅰ_3类细胞大都集中于视网膜的周边部位;介于两者之间的Ⅰ_2类细胞散在分布于整个视网膜。它们形成了空间分布上的中央—周边分化成熟梯度。(2)随着发育进程,Ⅰ_1类细胞数增多,分布区逐渐从中央向四周扩展,由占视网膜总面积的30%(P_1时)增至65%(P_6时),P_(13)时达97%。开眼后P_(13)时,由于Ⅰ_1类细胞分布已扩展至周边,中央区和周边区间细胞平均直径和树突发育成熟程度的差别逐渐缩小,Ⅰ型DA能无长突细胞发育成熟的中央—周边梯度明显减弱。至P_(23)时,周边区细胞对TH抗体免疫反应强度以及形态学上成熟程度均相似中央区者,上述中央—周边梯度特征则完全消失。I型DA能无长突细胞发育成熟过程中呈现时空顺序的中央—周边梯度特征是视网膜个体发育过程中的暂时现象,它与视网膜中一些神经发生过程存在平行关系。它在视网膜神经发生中的作用,文中进行了讨论。     

黑斑蛙视网膜3种神经内分泌细胞的免疫组织化学定位

目的研究神经肽Y(NPY)、五羟色胺(5-HT)和胰高血糖素(GLU)免疫阳性细胞在黑斑蛙(Rananigromaculata)视网膜上的组织学定位。方法应用过氧化物酶标记的链霉亲和素(SP法)免疫组织化学技术,并结合生物统计学分析。结果NPY细胞主要分布于内核层和节细胞层。内核层中出现两种阳性细胞,一种出现在第2、3亚层,常为多个细胞聚集;另一种出现在内侧,有突起伸入内网层。节细胞层阳性细胞分布较少,胞体有大小之分。5-HT细胞主要分布于内核层和节细胞层,位于内核层中邻近内网层一侧的阳性细胞有突起延伸入内网层。GLU细胞分布于外核层、内核层内侧以及节细胞层。结果 黑斑蛙视网膜上NPY、5-HT和GLU细胞的分布与其它物种有相似之处,也有其自身特点,符合其晨昏性生活习性。     

致病性Th17细胞在神经炎症中的作用及调控机制的研究进展

神经炎症是中枢神经系统在损伤、感染、毒素等各种影响内稳态因素的刺激下产生的复杂免疫反应,涉及驻留在中枢神经系统中的多种免疫细胞.持续存在的神经炎症是所有神经系统疾病(包括神经发育、神经退行性和精神性疾病)病因和病程的共同特性.Th17细胞是CD4+T细胞的一个重要亚型,在稳态条件下介导对细胞外细菌和真菌的免疫反应,维持...     

北京鸭视网膜节细胞的大小、密度和分布

采用Nissl染色法、视神经溃变法和神经元逆行追踪标记辣根过氧化物酶(HRP)法,研究了北京鸭视网膜节细胞(RGCs)的大小和密度及其分布的变化。北京鸭RGCs形态多样,有圆形、椭圆形和多角形等,RGCs总数为1.3×106个(P0),RGCs平均密度为5370个/mm2(P0),在视网膜中央有一个偏向鼻侧的高密度区即中央高密度区(8860个/mm2),由中央区至周边部,细胞密度逐渐降低,颞侧周边部最低(3440个/mm2)。不同区域RGCs大小差异显著,中央区以小细胞为主(62.2±23.3μm2,P0),而周边部RGCs逐渐增大,颞侧周边部最大(P0:133.7±75.7μm2;P8:152.9±55.9μm2)。由此可见,伴随RGCs大小由中央区至周边部的递增而细胞密度呈现递减的变化,这种变化趋势在颞侧周边部最明显。与此同时,随日龄增长,RGCs总数和密度均递减而细胞大小递增。dACs是位于视网膜节细胞层的小神经元,细胞大小为23.7±4.0μm2     

NPY样免疫反应在蝾螈发育过程中神经系统的定位研究

By immuno-cytochemical method the localization of neuropeptide Y (NPY) in the nervous system during embryonic development of Cynops orientalis was studied. The results revealed that NPY was first localized in the peripheral nervous system (late tail-bud stage), and later appeared in the central nervous system (larval stage) where it appeared with the appearance of glial cells. Very probably with the migration of neural crest cells NPY appeared first in the peripheral nervous system and then distributed to the central nervous system.     

Neuropeptide Y and peptide YY neuronal and endocrine systems

An extensive system of neuropeptide Y (NPY) containing neurons has recently been identified in the central and peripheral nervous system. In addition, NPY and a structurally related peptide, peptide YY (PYY), containing endocrine cells have been identified in the periphery. The NPY system is of particular interest as the peptide coexists with catecholamines in the central and sympathetic nervous system and adrenal medulla. Evidence has been presented which indicates that NPY may play important roles in regulating autonomic function.     

THE FORMATION AND STRUCTURE OF MYELIN SHEATHS IN THE CENTRAL NERVOUS SYSTEM

The development and structure of myelin sheaths have been studied in the optic nerves of rats and of Xenopus laevis tadpoles. Both potassium permanganate- and osmium-fixed material was examined with the electron microscope. In the first stage of myelinogenesis the nerve fibre is surrounded by a cell process which envelops it and forms a mesaxon. The mesaxon then elongates into a loose spiral from which the cytoplasm is later excluded, so that compact myelin is formed. This process is similar to myelinogenesis in the peripheral nervous system, although in central fibres the cytoplasm on the outside of the myelin is confined in a tongue-like process to a fraction of the circumference, leaving the remainder of the sheath uncovered, so that contacts are possible between adjacent myelin sheaths. The structure of nodes in the central nervous system has been described and it is suggested that the oligodendrocytes may be the myelin-forming cells.     

Co-localization of neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON)

Neuropeptide tyrosine (NPY) is one of the most abundant and widespread peptides in the mammalian nervous system. Recent isolation and sequencing of the DNA encoding NPY has predicted the existence of a 97 amino acid precursor peptide. Proteolytic processing of this precursor could yield three separate peptide products, an N-terminal signal peptide, neuropeptide tyrosine and a 30 amino acid C-terminal flanking peptide (C-PON). Here, we present evidence that the predicted C-flanking peptide of NPY is widely distributed in both the central and peripheral nervous systems of several mammalian species including man, and has an identical distribution to NPY. It was also demonstrated, using correlative light microscopic immunostaining on serial sections and double electron microscopic immunocytochemistry, that C-PON and NPY immunoreactivities are co-localized in neuronal cell bodies of the brain cortex, sympathetic ganglion cells, norepinephrine-containing granules of the adrenal medulla and in human pheochromocytoma tumor cells.     

Joint migration of gonadotropin-releasing hormone (GnRH) and neuropeptide Y (NPY) neurons from olfactory placode to central nervous system

The olfactory epithelium in vertebrates generates the olfactory sensory neurons and several migratory cell types. Prominent among the latter are the gonadotropin-releasing hormone (GnRH) neurons that differentiate within the olfactory epithelium during embryogenesis and migrate along the olfactory nerve to the central nervous system. We initiated studies to characterize additional neuronal phenotypes of olfactory epithelial derivation. Neuropeptide Y (NPY) neurons are functionally related to the reproductive axis, modulating the release of GnRH and directly enhancing GnRH-induced luteinizing hormone (LH) secretion from gonadotrophs. We demonstrate that a population of migratory NPY neurons originates within the olfactory epithelium of the chick. At stage 25, NPY-positive fibers, but not cells, were detected in the epithelium and the nerve. By stages 28–34, NPY neurons and processes were present in the olfactory epithelium, olfactory nerve, and at the junction of the olfactory nerve and forebrain. In these regions the number of NPY neurons increased until stage 30 and then declined as development progressed. Electron microscopic immunocytochemistry confirmed the neuronal phenotype of the NPY-positive cells. The origin and migratory nature of some of these NPY cells was confirmed by double-label immunocytochemical detection of NPY and GnRH. A large percentage of the NPY-cells coexpressed the GnRH peptide. Between stages 28 and 34 single- and double-labeled NPY and GnRH neurons were found side by side along the GnRH migratory route emanating from the nasal epithelium, along the olfactory nerve, and into the ventral forebrain. These data suggest that an NPY population originates in the olfactory epithelium and migrates into the central nervous system during embryogenesis. By stage 42, no NPY/GnRH double-labeled cells were detected. © 1996 John Wiley & Sons, Inc.     

Neuropeptide Y and autonomic nervous system

Neuropeptide Y (NPY) containing 6 amino acid residues belongs to peptides widely spread in the central and peripheral nervous system. NPY and its receptors play an extremely diverse role in the nervous system, including regulation of satiety, of emotional state, of vascular tone, and of gastrointestinal secretion. In mammals, NPY has been revealed in the majority of sympathetic ganglion neurons, in a high number of neurons of parasympathetic cranial ganglia as well as of intramural ganglia of the metasympathetic nervous system. At present, six types of receptors to NPY (Y₁–Y₆) have been identified. All receptors to NPY belong to the family of G-bound proteins. Actions of NPY on peripheral organs-targets are predominantly realized through postsynaptic receptors Y₁, Y₃–Y₅, and presynaptic receptors of the Y₂ type. NPY is present in large electrondense vesicles and is released at high-frequency stimulation. NPY affects not only vascular tone, frequency and strength of heart contractions, motorics and secretion of the gastrointestinal tract, but also has trophic effect and produces proliferation of cells of organs-targets, specifically of vessels, myocardium, and adipose tissue. In early postnatal ontogenesis the percent of the NPY-containing neurons in ganglia of the autonomic nervous system increases. In senescent organisms, this parameter decreases. This seems to be connected with the trophic NPY effect on cell-targets as well as with regulation of their functional state.     

神经肽Y和去甲肾上腺素在杏仁内侧核内影响血压和心率中的相互作用

分别向杏仁内侧核（ＭＡＮ）内微量注射去甲肾上腺素（ＮＡ）或神经肽Ｙ（ＮＰＹ）。ＮＡ引起血压升高,心率加快;而ＮＰＹ引起血压降低,心率减慢。如果注入不能改变血压的小剂量ＮＰＹ,则可抑制ＮＡ引起的升压作用,反映ＮＰＹ与ＮＡ共同参与心血管活动的中枢性调节过程。向ＭＡＮ中注射ＮＰＹ后血中ＮＡ的含量也相应降低,表明在ＭＡＮ中注射ＮＰＹ引起的血压、心率反应是通过降低血浆中ＮＡ含量而实现的。     

Neuropeptide Y receptors in rat brain: autoradiographic localization

Neuropeptide Y (NPY) receptor binding sites have been characterized in rat brain using both membrane preparations and receptor autoradiography. Radiolabelled NPY binds with high affinity and specificity to an apparent single class of sites in rat brain membrane preparations. The ligand selectivity pattern reveals strong similarities between central and peripheral NPY receptors. NPY receptors are discretely distributed in rat brain with high densities found in the olfactory bulb, superficial layers of the cortex, ventral hippocampus, lateral septum, various thalamic nuclei and area postrema. The presence of high densities of NPY and NPY receptors in such areas suggests that NPY could serve important functions as a major neurotransmitter/neuromodulator in the central nervous system.     

Neuropeptide Y: a putative neurotransmitter

Since its isolation in 1982, neuropeptide Y (NPY) has received considerable interest. This 36 amino acid peptide has been identified widely throughout the central and peripheral nervous systems, and within the autonomic system it appears in close association but not exclusively within catecholamine containing nerves. NPY begins to meet some of the criteria required to be established as a neurotransmitter. Thus, the peptide has been localised exclusively within nerves, and electron microscopy has shown NPY within nerve terminals. High affinity, saturable binding sites for NPY have been demonstrated in rat brain membranes, and the peptide has been reported to be released into the circulation during sympathetic nerve stimulation. The peptide is pharmacologically active both within the central nervous system by altering blood pressure, feeding and anterior pituitary function and in the periphery where NPY acts as a vasoconstrictor.