内源性甲醛异常蓄积与记忆衰退

近期,本实验室报道了内源性甲醛浓度与认知功能损伤程度之间的关系(Neurobiol Aging,2011,32(1):31-41).观察到转基因痴呆小鼠(APP、APP/PS1)及衰老加速型(SAMP8)小鼠脑内甲醛浓度较对照组显著升高.参照痴呆鼠脑内甲醛浓度,实验人员对正常成年小鼠进行注射,导致其视觉空间记忆能力减退.注射甲醛消除剂可以降低老龄大鼠体内甲醛浓度、减少APP痴呆模型小鼠脑内的老年斑,且能观察到记忆功能的改善.临床观察显示,老年痴呆患者尿甲醛浓度与认知功能损伤程度之间呈正相关.甲醛的过量蓄积造成脑慢性损伤,可能是散发性老年记忆衰退的机制之一.     

溶酶体离子通道蛋白在神经退行性疾病发生发展中的作用及机制研究

溶酶体离子通道蛋白异常引起溶酶体功能障碍是导致阿尔茨海默病(Alzheimer’s disease,AD)和帕金森病(Parkinson’s disease,PD)等神经退行性疾病的重要因素.溶酶体离子通道蛋白调节溶酶体内离子稳态、溶酶体膜电压以及溶酶体的酸度.溶酶体离子通道蛋白的结构或功能缺陷会引起溶酶体降解功能障碍,导致神经退行性疾病的发生发展.在这篇综述中,我们总结了各种离子通道蛋白调节溶酶体功能的过程及机制,以及离子通道蛋白异常参与神经退行性疾病的过程和机制.调节离子通道蛋白改善溶酶体的功能、促进异常聚集蛋白的清除,是神经退行性疾病治疗的潜在途径.     

研究: 慢性脱水中的脑甲醛代谢失调与学习迟缓

慢性脱水是阿尔茨海默病患者的临床表现之一,慢性脱水不但可以造成血清渗透压升高,同时也引起中枢神经系统代谢失调和认知损伤.本文通过配制4%Na Cl溶液作为C57 BL/6小鼠饮用水,连续喂养3个月,建立慢性脱水动物模型.慢性脱水(实验组)小鼠出现血清渗透压和Na+浓度升高、体重减轻等脱水症状.实验组小鼠在"穿梭箱"行为范式中表现学习迟缓,同时其脑内5-羟色胺显著降低,甲醛浓度升高,产生甲醛的氨基脲敏感氨氧化酶(SSAO)活性升高,并且活性升高的程度(脱水组酶活/对照组酶活)显著高于甲醛脱氢酶3(ADH3)的变化程度.腹腔注射甲醛溶液7天(每天1次)也导致小鼠的"穿梭箱"学习过程迟缓,并伴有脑内5-羟色胺下降;但在相同条件下,连续7天注射4%Na Cl溶液的小鼠组未见学习迟缓和5-羟色胺水平的降低.这些结果提示,慢性脱水导致小鼠脑内甲醛升高,5-羟色胺下降,可能是引起小鼠"穿梭箱"学习迟缓的原因之一.     

慢性脱水中的脑甲醛代谢失调与学习迟缓

慢性脱水是阿尔茨海默病患者的临床表现之一,慢性脱水不但可以造成血清渗透压升高,同时也引起中枢神经系统代谢失调和认知损伤.本文通过配制4%Na Cl溶液作为C57 BL/6小鼠饮用水,连续喂养3个月,建立慢性脱水动物模型.慢性脱水(实验组)小鼠出现血清渗透压和Na+浓度升高、体重减轻等脱水症状.实验组小鼠在"穿梭箱"行为范式中表现学习迟缓,同时其脑内5-羟色胺显著降低,甲醛浓度升高,产生甲醛的氨基脲敏感氨氧化酶(SSAO)活性升高,并且活性升高的程度(脱水组酶活/对照组酶活)显著高于甲醛脱氢酶3(ADH3)的变化程度.腹腔注射甲醛溶液7天(每天1次)也导致小鼠的"穿梭箱"学习过程迟缓,并伴有脑内5-羟色胺下降;但在相同条件下,连续7天注射4%Na Cl溶液的小鼠组未见学习迟缓和5-羟色胺水平的降低.这些结果提示,慢性脱水导致小鼠脑内甲醛升高,5-羟色胺下降,可能是引起小鼠"穿梭箱"学习迟缓的原因之一.     

病理浓度甲醛的累积导致小鼠神经母瘤细胞活力及黏附能力下降（英文）

衰老相关的认知损伤,如阿尔茨海默病(AD),是一种缓慢、渐进、不可逆的神经退行性疾病.内源(尿)甲醛浓度与AD病人的认知损害程度呈正相关.但是,在以前研究中所采用的甲醛浓度,通常高于AD患者和老年人的病理和生理浓度.因此,研究长时程低浓度(病理浓度)甲醛对神经类细胞的影响,对于揭示甲醛在AD发生发展过程的作用是非常必要的.本文参照AD患者尿甲醛浓度,采用每隔24 h连续传代接种加甲醛(10μmol/L)的方式,模拟AD病人尿甲醛浓度,观察长时程甲醛的累积对小鼠神经母瘤细胞(N2a)和原代海马神经元的影响.通过高效液相色谱、细胞活力和乳酸脱氢酶释放检测显示,随着孵育时间的延长,培养基内甲醛浓度积累升高,N2a细胞生长受到抑制,在甲醛孵育的后期,细胞死亡显著增加.全息成像显示,长时程病理浓度甲醛的积累,使细胞厚度增加、面积减小、神经突受损、显著削弱细胞的黏附能力.同样条件下,小鼠原代海马神经元的一级神经突的数目显著降低,表明病理浓度甲醛的积累能够削弱神经元之间的连接.免疫印迹和免疫荧光染色显示,甲醛的累积可以使N2a细胞内Tau蛋白的181位苏氨酸(T181)和396位丝氨酸(S396)磷酸化水平显著上升,可能是甲醛累积导致的神经突减少和形态改变的因素之一.以上结果证明,病理浓度甲醛在细胞生存环境中的累积,可以导致神经细胞损伤,尤其是神经突的异常改变.本文为探索甲醛代谢失调与老年认知损害之间关系和机制提供了新的启示.     

溶酶体生成的调控机制研究进展

自噬体和溶酶体是细胞维持稳态的重要系统,自噬体负责底物的识别和包裹,溶酶体负责底物的降解。溶酶体功能紊乱会导致细胞内物质不能被正常降解、致病性底物发生蓄积,进而诱发多种重大疾病,如溶酶体蓄积病(lysosomal storage disorders, LSDs)、神经退行性疾病和代谢性疾病等;相反,促进溶酶体生成,增强其降解功能则具有改善疾病的作用。因此,揭示并阐明溶酶体生成的调控机制是重要的科学问题。本文对溶酶体生成调控领域近年的研究进展进行综述。     

APP/PS1转基因老年性痴呆模型小鼠肠道甲醛浓度异常升高

【目的】肠道菌群通过"微生物-肠道-脑轴"影响中枢神经系统的功能,同时也与老年性痴呆的发生发展相关,特别是盲肠内微生物菌群的变化更为显著。肠道菌群可以产生和代谢甲醛,而肠道能够迅速吸收甲醛;体内甲醛含量与老年性痴呆病人的认知损害程度呈正相关。因此,本文比较了7月龄APP/PS1转基因老年性痴呆模型小鼠(简称APP/PS1转基因小鼠)与同月龄C57BL/6J野生型小鼠(简称C57BL/6J小鼠)肠道菌群产生甲醛的情况。【方法】取APP/PS1转基因小鼠(n=8)与C57BL/6J小鼠(n=9)的不同肠段(十二指肠、小肠、盲肠、结肠),采用2,4-Dinitrophenylhydrazi zne(DNPH)显色偶联高效液相色谱(HPLC coupled with DNPH)测定肠道消化物和肠壁组织的甲醛。【结果】APP/PS1转基因小鼠盲肠消化物内的甲醛含量,较C57BL/6J小鼠存在显著升高(P=0.036);而两者小肠和结肠消化物甲醛含量无显著差别。在两种小鼠之间,小肠壁内甲醛存在差异(P=0.052),而盲肠和结肠壁甲醛含量无显著差异(P0.05)。【结论】肠道菌群是小鼠体内甲醛的主要来源之一,无论肠道消化物,还是肠道壁组织均为盲肠的甲醛含量最高。这些结果表明,APP/PS1转基因小鼠肠道菌群存在甲醛代谢失调,从而导致其肠道消化物的甲醛含量升高。     

线粒体基因组在帕金森病发病机制中的作用

线粒体基因组以及线粒体呼吸链中酶复合体的改变会影响能量的供给,而脑对能量供给的改变非常敏感,甚至因此会引起神经细胞的死亡,导致神经退行性变的发生。由于脑组织不同的区域易感性不同,黑质纹状体部位的神经细胞容易引起氧化应激,导致自由基的升高,mtDNA发生突变,酶复合体功能下降,最终引起神经细胞的死亡,形成帕金森病的临床表现。     

缺血性脑卒中后神经元自噬流障碍的病理机制研究进展

自噬是一个将损伤细胞器、陈旧蛋白、多余胞质组分甚至病原体等通过自噬体呈递给溶酶体进行降解的细胞内代谢过程。它包括自噬启动、自噬体形成、自噬体-溶酶体融合和自噬底物在自噬溶酶体内降解和清除4个步骤。当这些过程呈连续通畅状态则可称为自噬流,自噬/溶酶体信号通路中某一或某些步骤发生阻滞均可导致自噬流障碍。众多研究表明,脑卒中后自噬流障碍是导致脑卒中后缺血半影区神经元损伤的重要原因。本文总结了缺血性脑卒中后神经元自噬流障碍的病理机制研究进展,并介绍了目前改善神经元自噬流障碍方法的研究进展,为深入探究脑卒中病理损伤机制提供参考。     

受体介导内吞引起的巨噬细胞胞质酸化和胞吐作用

本文利用激光扫描共聚焦显微镜A-CAS570从细胞形态学和功能两方面,研究了刀豆素A(Concanavalin A,Con A)、麦芽凝集素(Wheat Germ Agglutinin,WGA)、酵母多糖(Zymosan A,Z.A)对小鼠腹腔巨噬细胞胞质pH和溶酶体内荧光探针FITC—Dextran排出细胞的影响。结果显示三种配体加入细胞外液10min内,胞质pH很快下降,此后维持在该水平;在15min左右细胞外FITC一Dextran迅速增加,20min后变化趋于停止;在三种配体加入后15min左右,细胞内溶酶体在质膜内侧增多;25—30min溶酶体重新向细胞中央运动。根据上述实验结果,我们认为溶酶体pH升高是触发溶酶体内荧光探针通过胞吐作用排出细胞的必要条件,胞质酸化抑制溶酶体内容物通过胞吐作用排出细胞。配体刺激引起的溶酶体内容物通过胞吐作用排出细胞和胞质酸化是细胞自我调节和保护的一种反映。     

六种藓类植物茎的比较解剖学研究

通过对6种藓类植物,即褶叶青藓(Brachythecium salebrosum(Web.et Mohr.)B.S.G.)、湿地匐灯藓(Plagiomnium acutum(Lindb.)Kop.)、侧枝匐灯藓(Plagiomnium maximoviczii(Lindb.)Kop.)、大凤尾藓(Fissidensnobilis Griff.)、大羽藓(Thuidium cymbifolium(Doz.et Molk.)B.S.G.)和大灰藓(Hypnum plumaeforme Wils.)嫩茎和老茎的石蜡切片和显微观察发现,同一藓类植株的嫩茎和老茎,茎结构稳定,不同种藓类植物茎横切面具有不同特征.植物体茎横切面形状、表层细胞的层数、细胞大小和细胞壁厚薄、皮层细胞大小和形状、中轴的有无以及比例等特征可以作为藓类植物的分科分类依据之一.     

Cause of Senescence of Nine Sorts of Flowers

The levels of endogenous phytohormones and respiratory rate in nine sorts of flowers such as Cymbidium faberi Rolfe, Nopalxochia ackermannii Kunth and others were investigated both at full bloom and senescence and meanwhile the effect of exogenous phytohormones on prolonging the blossoms and promoting ethylene production were tested. There is a high content of endogenous ethylene in all the long-lived flowere, about 3–16 folds higer than the short-lived ones. There is a high level of ABA at full blooming flowers of short-lived flowers, in which there is no or only some cytokinins in it, but the ratio of CTK (6BA+zeatin)/ABA is smaller(l.7). The endogenous ABA reached a much higher level at senescence in all nine sorts of flowers, so it is reasonable to consider that it is ABA which plays an important role of regulation in controlling flower's senescence. There is a much higher level of GA3 and zeatin in the long-lived flowers which is not demonstrated in the shortlived ones. The respiratory rate is one of the factors controtling the longevity of flowers, but it does not play a decided role. Application of 6BA and zeatin prolongs distinctly orchid’s longevity, however exogenous IAA through the promotive action on ethylene production, evidently extends the longevity of the flowers of the Nopalxochia ackermannii Kunth.     

Photoregulation of seed germination of wild-type and of an aurea-mutant of tomato

Seed germination of an aurea mutant of tomato ( Lycopersicon esculentum Mill.) is promoted by continuous irradiation with red, far-red or long-wavelength far-red (758 nm) light as well as by cyclic irradiations (5 min red or 5 min far-red/25 min darkness). Far-red light applied immediately after each red does not change the germination behaviour. Seed germination of the isogenic wild-type, cv. UC-105, is promoted by continuous and cyclic red light while it is inhibited by continuous and cyclic far-red light and by continious 758 nm irradiation. Far-red irradiation reverses almost completely the promoting effect of red light. The promoting effect (in the aurea mutant) and the inhibitory effect (in the wild-type) of continuous far-red light do not show photon fluence rate dependency above 20 nmol m⁻² s⁻¹. It is concluded that phytochrome controls tomato seed germination throgh low energy responses in both the wild type and the au mutant. The promoting effect of continuous and cyclic far-red light in the au mutant can be attributed to a greater sensitivity to P_fr.     

真菌类遗传学分析的知识结构教学

本文以认知结构理论为指导,讨论了真菌类遗传分析与高等动植物遗传分析的内在联系,认为利用这种内在联系进行教学可收到好的效果并说明了作者的具体教学过程。 Abstract:In the paper, the relationship between genetic analysis of Fungi and genetic analysis of high animal and plant was discussed.A good results were obtained when we adopted this method in the teaching.     

龙胆科药用植物化学成分的研究现状

龙胆科植物在我国的分布范围很广,且多数为药用植物,其多数种属的药用植物,至今其化学成分尚未被系统研究。综述了目前龙胆科药用植物的化学成分的研究现状及一般提取方法,对近年来发现的环烯醚萜及裂环烯醚萜类化合物进行了总结,为本科药用植物的更深入研究提供了参考。     

The effects of glutamine of the maintenance of embryogenic cultures of Cryptomeria japonica

Summary Embryogenic tissues of sugi (Cryptomeria japonica) were induced on a modified Campbell and Durzan (CD) medium containing 1 μM 2,4-dichlorophenoxyacetic acid (2,4-D) and 600 mg l⁻¹ glutamine, and subcultured in the medium of the same composition for over 1 yr. This resulted in a mixed culture of embryogenic and non-embryogenic cells. When embryogenic cells were isolated and cultured independently, their capacity to form embryogenic aggregates was lost. Thus, the non-embryogenic cells present within a mixed culture system were essential to the formation of embryogenic aggregates. When embryogenic tissues were isolated and cultured independently on a high glutamine-containing (2400 mg l⁻¹) medium, dry weights and endogenous levels of glutamine increased, and the tissue could generate a large number of embryogenic aggregates. Amino acid analysis of embryogenic and non-embryogenic cells from the maintenance culture indicated a higher level of glutamine was present in the latter. The high endogenous level of glutamine in the non-embryogenic portion of mixed cell masses may be the supplier of glutamine for maintaining the embryogenic property of the tissues.     

Specificity of action of piperidylcholine derivatives as substrates of cholinesterases of various origin

The review deals with study of enzymologic properties of a novel highly specific acetylcholinesterase substrate, N-(β-acetoxyethyl) piperidinium iodomethylate (“piperidylcholine”), and its 30 derivatives that were tested as effectors of cholinesterases of mammals and various species of Pacific squids. It was proven for the first time that responsible for specificity of action was structure of cyclic ammonium grouping of the alcohol part of molecule of the ester substrate. Analysis of specificity is performed based on enzymatic hydrolysis parameters—activity of catalytic center of cholinesterases and bimolecular constant of the reaction rate that are determined at optimal and low substrate concentrations. Among the specially synthesized group of thioester compounds there is revealed one more highly specific acetylcholinesterase substrate—N-(β-acetoxyethyl) piperidinium.     

Interconnection of parameters of regulation system of lipid peroxidation and of morphophysiological parameters of mouse liver

A complex analysis of seasonal fluctuations of the mean group parameters of the system of regulation of lipid peroxidation has been performed in liver of Balb/c mice. Association of lipid characteristics and morphophysiological parameters is studied in the Balb/c mouse liver. An inter-connection is revealed between the liver index and the amount of lysoforms of phospholipids, the scale and character of the interconnection differing essentially depending on proportion of phos-phatidylcholine in mouse liver phospholipids.