内源性甲醛参与调节记忆

甲醛是地球上进化早期阶段最早出现的同时含有C、H、O元素的最简单有机小分子之一,被发现存在于每一个真核细胞中,并参与"一碳代谢"。近期研究表明,内源性甲醛可能作为信号分子参与记忆的形成。电刺激或学习训练后,大鼠脑内甲醛含量瞬时升高,激活N-甲基-D-天冬氨酸(N-methyl-D-aspartate, NMDA)受体,促进长时程增强(long-term potentiation,LTP)或空间记忆的形成。相反,降低脑内甲醛含量后,NMDA受体不能被激活,不能形成LTP和短时记忆。在正常老年大鼠和阿尔茨海默病转基因小鼠中,脑内甲醛浓度异常升高,NMDA受体活性受到抑制,空间记忆受损。因此,维持体内生理水平的甲醛浓度对于记忆的形成与储存尤为必要。本文对内源性甲醛在学习和记忆中的生理与病理生理学功能进行了综述。     

内源性甲醛与心血管疾病

内源性甲醛是甲胺由氨基脲敏感性胺氧化酶催化而生成,广泛存在于动物体内多种组织细胞。已经证实,内源性甲醛参与了神经变性病、免疫性疾病以及肿瘤等疾病的发病过程。脂肪细胞、血管内皮细胞和平滑肌细胞富含甲醛生成酶氨基脲敏感性胺氧化酶(semicarbazide-sensitive a-mine oxidase,SSAO)。甲醛具有细胞毒性,易损伤血管内皮并介导多种致病因素诱导的血管损伤过程,在动脉粥样硬化和糖尿病及其并发症的发病中都具有重要作用。     

老年性痴呆发病过程中内源性甲醛慢性损伤机制

通过原子力显微镜、荧光标记、Congo染色等方法,观察到低浓度甲醛可以诱导人类神经Tau蛋白错误折叠并形成具有细胞毒性的似球状聚积物;气相色谱和液相色谱等分析结果表明,神经鞘磷脂N-Acyl-4-sphingoine-1-phosphocholine (myelin的过氧化能够产生甲醛分子;脂质过氧化的代谢产物丙二醛(malondialdehyde)在修饰蛋白质(BSA)的过程中,亦可产生甲醛分子.以上结果为内源性甲醛的产生揭示了新的途径.值得注意的是,在生理条件下,血液中内源性甲醛的水平维持在一个动态平衡((0.087±0.004)retool/L),与体外培养神经细胞时甲醛产生毒性的浓度(～0.1 mmol/L)十分接近,甚至已经达到产生一定细胞毒性的水平.随着机体的衰老,内源性甲醛的调节机能下降,在氧化应激等相关因素的诱导作用下,内源性甲醛浓度可能升高,对中枢神经系统一定部位的神经细胞造成慢性损伤,这可能是散发性老年痴呆发病的机制之一.     

菟丝子总黄酮对内分泌衰退痴呆模型小鼠学习记忆功能的影响及保护作用机制

目的:研究菟丝子总黄酮对内分泌衰退痴呆模型小鼠学习记忆功能的影响,并探讨其可能的作用机制。方法:将50只昆明种雌性小鼠随机分为模型组,雌激素对照组(0.3 mg·kg-1),菟丝子总黄酮低剂量组(35mg·kg-1),菟丝子总黄酮中剂量组(70 mg·kg-1)和菟丝子总黄酮高剂量组(140 mg·kg-1),采用背部去卵巢法切除双侧卵巢,另取10只小鼠作为假手术对照组,建立内分泌衰退小鼠模型,术后各治疗组进行灌胃给药治疗三个月,假手术组和模型组均给予0.9%生理盐水。给药结束后采用Morris水迷宫观察小鼠行为学变化;放射免疫法检测小鼠血液中雌激素的水平;HE染色光镜观察海马神经元病理形态;流式细胞仪检测小鼠海马神经细胞凋亡率和免疫印迹法检测海马区神经细胞凋亡相关蛋白(Bcl-2、Bax、Csapase-3)及Cyt-c蛋白的表达水平。结果:与假手术组相比,模型组小鼠学习记忆能力明显下降(P0.01);血液中雌激素水平显著降低(P0.01);海马神经细胞凋亡率显著增加(P0.01);Cyt-c、Caspase-3、Bax蛋白表达水平大大增加(P0.01),Bcl-2蛋白表达降低明显(P0.01)。与模型组相比,TFSC各治疗组小鼠学习记忆能力显著增强(P0.05,P0.01,P0.01);血液中雌激素水平上升显著(P0.05,P0.01,P0.01);小鼠海马区神经细胞凋亡率明显下降(P0.05,P0.01,P0.01);同时Cyt-c、Caspase-3、Bax蛋白表达水平均大大降低,Bcl-2蛋白表达均明显增加(P0.05,P0.05,P0.01)。结论:TFSC可上调脑细胞中Bcl-2蛋白的表达水平,抑制Bax、Caspase-3和Cyt-c蛋白的表达量,进而增强神经元的可塑性和营养性,以防止神经细胞从内源性线粒体途径丢失或凋亡,进一步改善内分泌衰退型痴呆小鼠的学习记忆能力。TFSC可能是通过促进或增强下丘脑-脑垂体-性腺轴功能,从而达到增加雌激素水平和改善内分泌系统功能的目的。     

甲醛导致细胞周期异常的浓度选择性

一定浓度的甲醛可以引起蛋白质的异常修饰、功能丧失、细胞死亡。虽然甲醛的细胞毒性已见报道,但甲醛影响神经细胞周期及其分子机制等尚不明确．本文采用不同浓度甲醛与神经母细胞瘤细胞系SH-SY5Y共孵育,观察到甲醛对细胞周期的影响取决于甲醛的浓度．当甲醛浓度([FA])≤0.1 mmol/L(细胞培养48 h),细胞周期与对照相比,无显著性差异．当甲醛浓度增加(0.1 mmol/L <[FA]≤0.2 mmol/L),S期和G2/M期细胞比例显著增加;当[FA] = 0.3 mmol/L时,细胞增殖被显著抑制,大量细胞滞留在S期(46.28%),G2/M期细胞仅占16.05%．将细胞同步到G2/M期,用0.1～0.3 mmol/L甲醛孵育,尽管G2/M期细胞都有一定程度的减少,但S期细胞显著增加;将细胞同步化到S期,与0.1 mmol/L甲醛孵育,则G2/M期细胞有一定程度的减少;与0.3 mmol/L甲醛孵育,表现为G2/M细胞显著减少,S期细胞极度增加．在相同条件下,Sprague-Dawley (SD)大鼠原代皮层神经元,也表现出G2/M期细胞比例随甲醛浓度升高而降低,S期细胞比例随之增加的现象．当0.1 mmol/L≤[FA]≤0.2 mmol/L时,细胞出现明显的早期或晚期凋亡;当[FA]≥0.3 mmol/L时,DNA损伤明显,细胞出现凋亡和部分坏死．以上结果提示,低浓度甲醛(0.1 mmol/L≤[FA]≤0.2 mmol/L)主要通过引起DNA超甲基化而抑制S期DNA的合成,高浓度甲醛([FA]≥0.3 mmol/L)则造成DNA的损伤,从而影响细胞周期的进程．     

壶菌病与两栖动物的种群衰退

两栖类种群全球性衰退是21世纪最紧迫的环境问题之一。越来越多的证据表明壶菌(Batrachochytrium dendrobatidis)与澳大利亚、美洲北部、中部、南部及欧洲的两栖类种群衰退有关。由壶菌引起的壶菌病是变态后的无尾类所患的一种显性传染病,其令人质疑的快速传播及广泛爆发对世界范围内的两栖类种群构成重大威胁。本文对这种致病壶菌的病理学、生态学、生物地理学及其治疗方面的进展进行了综述。     

令人烦恼的记忆

记载着挫折、恐惧、绝望等负性情绪的负性记忆,具有难以遗忘、令人烦恼的特点,与一些脑重大疾病,如创伤后应激综合征、抑郁症等存在密切关系。研究表明NMDA受体依赖性长时程增强在记忆的获取、储存等过程中起着关键作用。电休克和NMDA受体拮抗剂氯胺酮已知可导致短暂性遗忘,应用于治疗创伤后应激综合征、抑郁症具有起效快、疗效好的显著特点,提示这类脑疾病可能与负性记忆的遗忘特点有关。最近报道,遗忘具有独立的分子机理,在记忆和遗忘机理的共同作用下,既可能发生"记不住"如老年痴呆症、也可能出现"忘不了"如创伤后应激综合征和抑郁症等。深入研究遗忘的细胞分子机理,无疑有助于我们认识、预防和治疗相关脑重大疾病。     

腹部手术与肠道细菌移位和内源性感染

目的 人体肠道定植着大量的细菌,正常情况下肠道菌群与机体处于动态平衡,腹部外科手术的刺激和创伤可以破坏肠道正常的菌群结构和屏障功能,使细菌的数量、比例发生改变或空间上发生移位,引发内源性感染,最终导致机体各种功能障碍.研究分析腹部外科手术对肠道细菌及屏障功能的影响,为今后预防和治疗提供理论依据.     

避暗反应测定大鼠学习记忆功能方法的探讨

目的 为了提高避暗反应测定动物学习记忆功能的敏感性,本实验对三种实验及统计方法进行了评价。方法 采用IBO致基底前脑胆碱能神经元损伤模型和东莨菪碱所致的记忆障碍模型,对单次简单测试法、多次简单测试法和多次记分测试法的敏感性进行了比较。结果 对于基底前脑损伤模型,单次简单测试法的潜伏期学习记忆指标无法显示出模型组与对照组之间的差异。多次简单测试法两种指标均能显示出显著性差异,且较多次记分测试法的指标差异的显著性高。对于东莨菪碱致痴呆模型,也有同样的效果。结论 多次简单测试法更能敏感地反映动物的学习记忆功能。     

老年学习记忆减退的神经行为学基础

用改良Ｍｏｒｒｉｓ水迷宫将老年大鼠分为老年学习记忆减退组和老年学习记忆正常组,并与青年组对照,检测其空间参考记忆和空间工作记忆,并对海马结构内胶质纤维酸性蛋白（ＧＦＡＰ）阳性胶质细胞和ＧＡＢＡ能中间神经元在光镜和电镜水平进行定量分析。结果显示老年学习记忆减退大鼠的空间参考记忆能力明显下降,并且其行为模式发生了改变,空间工作记忆改变不明显;齿状回分子层的病理改变非常明显,表现为ＧＡＢＡ能神经元丢失和     

Aging‐associated formaldehyde‐induced norepinephrine deficiency contributes to age‐related memory decline

A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging‐associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age‐related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6‐hydroxydopamine (6‐OHDA, a NE depletor) can mimic age‐related NE deficiency, long‐term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age‐related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence‐accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age‐matched, senescence‐resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging‐associated NE depletion and cognitive decline.     

生态学中的植物记忆研究

近年来,植物记忆研究为深入理解种群分布格局、群落构建、群落演替等生态学过程提供了新的视角,因此备受生态学家的关注。在介绍生态胁迫记忆、表观遗传记忆、生态记忆、土壤记忆概念的基础上,综述了近几年来相关领域在生态学研究中的最新进展,并提出了植物记忆在生态学研究中值得关注的方向,以期为全面深入的理解生态学过程提供一个新的角度。     

The relationship between visual working memory and attention: retention of precise colour information in the absence of effects on perceptual selection

We examined the conditions under which a feature value in visual working memory (VWM) recruits visual attention to matching stimuli. Previous work has suggested that VWM supports two qualitatively different states of representation: an active state that interacts with perceptual selection and a passive (or accessory) state that does not. An alternative hypothesis is that VWM supports a single form of representation, with the precision of feature memory controlling whether or not the representation interacts with perceptual selection. The results of three experiments supported the dual-state hypothesis. We established conditions under which participants retained a relatively precise representation of a parcticular colour. If the colour was immediately task relevant, it reliably recruited attention to matching stimuli. However, if the colour was not immediately task relevant, it failed to interact with perceptual selection. Feature maintenance in VWM is not necessarily equivalent with feature-based attentional selection.     

甲醛胁迫下四种盆栽植物的生理动态反应

选择巢蕨(Neottopteris nidus)、巴西铁(Dralaena fragrans)、虎尾兰(Sansevieria trifasciata)和黑美人(Aglaonema commutatum)4种室内盆栽植物作为典型的试验材料,以15 mg·m-33甲醛分别进行熏蒸处理,测定单位干物质甲醛的吸收量、相对电导率、丙二醛含量和叶绿素含量等,以研究这些植物在甲醛胁迫下的生理动态反应。结果表明:在甲醛胁迫的4 d时间内,巢蕨和巴西铁的单位干物质甲醛吸收量均在第3天达到峰值,而黑美人和虎尾兰则一直在缓慢增加,其中以巢蕨吸收的量最多,巴西铁单位干物质甲醛吸收量最少; 4种植物的相对电导率、丙二醛的含量均随甲醛胁迫时间的增加而增加,以巢蕨的相对电导率最高,虎尾兰最低,但巴西铁的丙二醛的含量最高,巢蕨最低; 4种植物的叶绿素含量均随甲醛胁迫时间的增加而降低,其中黑美人降低幅度最高,虎尾兰最低。     

盐胁迫环境下不同抗盐性小麦品种幼苗长势和内源激素的变化

采用两种浓度NaCl溶液,对不同抗盐性小麦品种德抗961(抗盐性强)和泰山9818(抗盐性弱)萌发期幼苗进行胁迫处理,观察其幼苗长势和内源激素含量变化.结果表明,盐胁迫抑制小麦幼苗生长,抗盐性弱的泰山9818受抑制较重.苗、根ABA含量随盐胁迫浓度增加而提高,泰山9818的增幅高于德抗961.苗、根IAA含量随盐胁迫浓度增加而降低,但德抗961的IAA含量高于泰山9818,说明盐胁迫下抗盐性强的品种具有较高IAA合成量.2品种GA3含量变化因盐胁迫浓度而异.在低盐胁迫下抗盐性强的品种苗中GA3含量提高以适应盐胁迫利于苗的生长,在高盐胁迫下2品种GA3含量降低.盐胁迫使苗中ZR含量增加,且德抗961的苗中ZR含量高于泰山9818,而根中ZR含量则前者低,说明盐胁迫下抗盐性强的品种可迅速将根部合成的ZR向苗中转移,促进苗的生长.2品种IAA/ABA、GA3/ABA比值随盐胁迫浓度增加和时间延长而下降,德抗961 IAA/ABA比值大于泰山9818.在盐胁迫下,抗盐性强的品种协调自身激素平衡的能力较强可能是其生长受抑制较小的重要原因.     

Neurogenesis in a rat model of age-related cognitive decline

Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.     

Food-specific spatial memory biases in an omnivorous bird

The tendency of nectarivorous birds to perform better on tasks requiring them to avoid previously rewarding locations (to win-shift) than to return to them (win-stay) has been explained as an adaptation to the depleting nature of nectar. This interpretation relies on the previously untested assumption that the win-shift tendency is not associated with food types possessing a different distribution. To test this assumption, we examined the specificity of this bias to different food types in an omnivorous honeyeater, the noisy miner (Manorina melanocephala). As predicted, we found that the win-shift bias was sensitive to foraging context, manifesting only in association with foraging for nectar, not with foraging for invertebrates.