脑衰老的细胞学研究

脑是有机体衰老过程中最突出的器官,也是人和动物老年性功能障碍的主要病灶之一。本文阐述了衰老脑的特征、衰老动物在机能方面所表现的机能障碍、脑衰老机理的研究概况和改变脑衰老过程的一些措施。指出,目前用于脑衰老研究的主要是啮齿类鼠、兔等动物模型,其研究结果很难肯定完全符合于灵长类或其它脊椎动物。因此,动物模型的建立和评价已经成为脑衰老研究的当务之急。     

蜂花粉抗脑衰老的实验动物研究

蜂花粉抗脑衰老的实验动物研究蒋滢,杨炳华,黄美英苏州医学院生化教研室苏州２１５００７２探索衰老机制,寻求延缓衰老的有效途径是生命科学中的重大问题,也是亟待解决的实际问题。脑是指挥全身一切活动的中枢,脑组织特别容易遭受自由基及活性氧的损伤,因此防治脑衰...     

长链非编码RNA与脑衰老的研究进展

长链非编码RNAs(long non-coding RNAs,lnc RNAs)参与调控诸多生命过程,与大脑发育、脑衰老以及脑衰老相关疾病的发生与发展密切相关。因此,发现lnc RNAs,预测并研究lnc RNAs的特征、结构、功能和作用机制,有助于我们更加系统、深入地了解lnc RNAs参与调控生命发育、衰老和疾病发生发展等过程的功能机理,促进lnc RNAs的相关成果向临床治疗转化。现就lnc RNAs和脑衰老相关lnc RNAs的研究现状和研究思路进行综述。     

脑的氧自由基代谢

中枢神经系统氧自由基代谢的资料 ,是从对衰老及一些精神疾患—主要是老年性痴呆 (Ａｌｚｈｅｉｍｅｒ’ｓＤｉｓ ｅａｓｅ ,ＡＤ)—的研究中获得的。虽然 ,现有资料尚欠全面和系统 ,但不难看出其变化规律有别于脑以外其它脏器及组织的氧自由基代谢。这说明了脑在代谢方面的复杂性和特殊性。且提示 :脑的氧自由基代谢 ,在衰老及ＡＤ的发生发展中的作用是重要的。概括地讲 ,衰老及ＡＤ均表现为渐进性脑功能退化 ,且中枢神经系统的病理变化亦存在着质的相似之处。这说明二者在其发生发展的相关因素中 ,某些是相同的 ,脑的氧自由基代谢紊乱可能…     

综述:脑衰老与阿尔茨海默病症状出现前阶段

脑衰老可分为生理性增龄变化与病理性变化,后者与阿尔茨海默病(Alzheimer's disease,AD)等神经退行性疾病的发生有关．生理性脑衰老与AD在发病早期具有相似的表现形式、病变特征、生化改变和发病机制．其共同的分子机制是异常蛋白质蓄积,提示两者有着相似的病理学基础,脑衰老可能是AD等神经退行性改变的最初级阶段,病理性脑衰老因素可能促进AD等神经退行性疾病的发生发展．临床前期AD(preclinical AD,PCAD)患者的脑、血液和脑脊液中可以检测到AD特定的生物标记物,但AD的临床症状并没有出现,因此也被称为“症状出现前AD(presymptomatic AD)”．PCAD和对照组比较,氧化应激指标和高度不溶性Aβ42并没有显著性升高,寻找早期PCAD发病过程中新的可用于临床早期诊断的生物标记物、药物靶点将成为我们的关注重点．     

多巴胺信号系统在衰老引起的行为和认知能力退化中的作用

衰老是生物体随时间推移各项生理功能逐渐发生改变的自然现象。动物的衰老伴随着行为和认知能力的降低,因此研究动物行为和认知功能退化的分子神经机制对于提高老年群体的生活质量具有重要意义。近年来,随着正电子发射断层扫描技术和功能性核磁共振脑成像技术在神经生物学上的广泛运用,越来越多证据表明多巴胺系统功能在衰老过程中显著降低,并且这是人类和动物行为和认知功能退化的重要原因。本文将概述自然衰老过程中多巴胺信号系统功能变化及机制和其在动物行为和认知退化中的作用等方面研究进展。     

靶向脑衰老胶质细胞的运动防治PD研究进展

细胞衰老是一个体内平衡的生物过程,在推动机体衰老过程中起着关键作用。衰老细胞在神经系统中随着衰老和神经退行性疾病而积累,并且可能使人易患神经退行性疾病或加重其病程。帕金森病(Parkinson's disease,PD)是一种与年龄相关的神经退行性疾病。运动可通过提高衰老过程中脑细胞自噬水平,增强神经免疫信号分子以及脑内脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达有效预防或延缓脑细胞衰老甚至清除脑衰老细胞,维持脑健康。大量流行病学调查结果以及临床和基础研究证实,不同形式的运动锻炼/身体活动均可改善PD患者或者PD模型动物的症状或改善症状的发展。本文以脑衰老胶质细胞为切入点,充分阐明脑衰老胶质细胞在PD中的作用以及运动干预对PD脑衰老胶质细胞的影响,以便有效和安全地利用脑衰老胶质细胞作为潜在的治疗靶点,以期为运动干预减缓(和)或改善PD运动功能障碍的神经生物学机制研究提供新的思路,为探寻PD的非药物防治或辅助疗法提供理论基础。     

花粉制剂对脑衰老动物各脑区的SOD和NO水平的影响

采用 D-半乳糖建立脑衰老动物模型 ,观察服用花粉制剂前后对脑衰老模型动物不同脑区组织中超氧化物歧化酶 ( SOD)活性、一氧化氮 ( NO)水平的影响。结果表明花粉制剂能明显升高脑衰老动物某些脑区 SOD活性和降低脑衰老动物某些脑区 NO水平。研究结果提示花粉制剂具有延缓衰老和增强记忆力等作用 ,其机制可能与其促进自由基的清除及减少 NO释放有关。     

组织蛋白酶B参与脑衰老及阿尔兹海默症发生发展研究进展

组织蛋白酶B (cathepsin B,CatB)是一种定位于溶酶体的半胱氨酸蛋白酶，最初被认为在溶酶体内发挥非选择性地降解吞噬或者自噬蛋白的功能。然而最新研究发现，CatB也可以选择性地降解或特异性地活化目标蛋白，从而参与调控生理病理反应。在衰老及相关的神经退行性疾病的大脑中，CatB的表达、酶活性及细胞定位都发生了显著变化，因此CatB在衰老和神经退行性疾病中的病理学功能备受关注。本文对CatB参与脑衰老及阿尔兹海默症进程的相关研究进行了系统梳理，并讨论了目前有关CatB的神经病理学研究中存在的问题，以期为全面认识脑衰老及阿尔兹海默症的病理机制奠定基础。     

运动延缓脑衰老的实验研究

运动是延缓脑衰老的重要手段之一。以“跑转笼”方式建立运动动物模型,用行为学、形态学和生物学研究方法,研究从青年开始的长期运动（８ｍｏ,１９ｍｏ）对运动相关中枢随年龄增加而出现的退行性变化的作用及作用机制。结果表明,长期适量运动能够延缓运动相关中枢随年龄增加而出现的形态结构和功能的退行性变化,通过促进神经元结构代偿而改善神经元功能。     

Genetic links between brain development and brain evolution

The most defining biological attribute of Homo sapiens is its enormous brain size and accompanying cognitive prowess. How this was achieved by means of genetic changes over the course of human evolution has fascinated biologists and the general public alike. Recent studies have shown that genes controlling brain development - notably those implicated in microcephaly (a congenital defect that is characterized by severely reduced brain size) - are favoured targets of natural selection during human evolution. We propose that genes that regulate brain size during development, such as microcephaly genes, are chief contributors in driving the evolutionary enlargement of the human brain. Based on the synthesis of recent studies, we propose a general methodological template for the genetic analysis of human evolution.     

Selenium and selenoproteins in the brain and brain diseases

Over the past three decades, selenium has been intensively investigated as an antioxidant trace element. It is widely distributed throughout the body, but is particularly well maintained in the brain, even upon prolonged dietary selenium deficiency. Changes in selenium concentration in blood and brain have been reported in Alzheimer's disease and brain tumors. The functions of selenium are believed to be carried out by selenoproteins, in which selenium is specifically incorporated as the amino acid, selenocysteine. Several selenoproteins are expressed in brain, but many questions remain about their roles in neuronal function. Glutathione peroxidase has been localized in glial cells, and its expression is increased surrounding the damaged area in Parkinson's disease and occlusive cerebrovascular disease, consistent with its protective role against oxidative damage. Selenoprotein P has been reported to possess antioxidant activities and the ability to promote neuronal cell survival. Recent studies in cell culture and gene knockout models support a function for selenoprotein P in delivery of selenium to the brain. mRNAs for other selenoproteins, including selenoprotein W, thioredoxin reductases, 15-kDa selenoprotein and type 2 iodothyronine deiodinase, are also detected in the brain. Future research directions will surely unravel the important functions of this class of proteins in the brain.     

Human brain natriuretic peptide-like immunoreactivity in human brain.

The presence of immunoreactive human brain natriuretic peptide in the human brain was studied with a specific radioimmunoassay for human brain natriuretic peptide-32. This assay showed no significant cross-reaction with human alpha atrial natriuretic peptide, porcine brain natriuretic peptide or rat brain natriuretic peptide. Immunoreactive human brain natriuretic peptide was found in all 5 regions of human brain examined (cerebral cortex, thalamus, cerebellum, pons and hypothalamus) (0.6-6.7 pmol/g wet weight, n = 3). These values were comparable to the concentrations of immunoreactive alpha atrial natriuretic peptide in human brain (0.5-10.1 pmol/g wet weight). However, Sephadex G-50 column chromatography showed that the immunoreactive human brain natriuretic peptide in the human brain eluted earlier than synthetic human brain natriuretic peptide-32. These findings suggest that human brain natriuretic peptide is present in the human brain mainly as larger molecular weight forms.     

The spread of brain oedema in hypertensive brain injury

Severe hypertension in humans may lead to fibrinoid necroses of cerebral blood vessels with small hemorrhages and cystic necroses. Similar lesions have also been reported in the experimental model of stroke-prone spontaneously hypertensive rats (SHRSP). We examined the genesis and spreading pattern of the brain oedema in SHRSP. The extravasation of plasma proteins was visualized with the Evans-Blue or the immunoperoxidase method. Most commonly the leakage occurred in the grey matter of the cerebral cortex or basal ganglia. The spreading pattern followed that of vasogenic brain oedema with a local spread in the grey matter and an extensive one in the white matter. In addition, we detected a novel pathway upwards along the perivascular spaces of the penetrating vessels as well as laterally in the subpial zone. This route is likely to serve also as a drainage channel for the oedema into the cerebrospinal fluid in the subarachnoidal space. Transfer of the extravasated proteins from the white matter to the ventricles was also observed, confirming that this previously described pathway for the resolution of oedema fluid exists in the SHRSP model of vasogenic brain oedema.     

Microglia in development: linking brain wiring to brain environment

Microglia are enigmatic non-neuronal cells that infiltrate and take up residence in the brain during development and are thought to perform a surveillance function. An established literature has documented how microglia are activated by pathogenic stimuli and how they contribute to and resolve injuries to the brain. However, much less work has been aimed at understanding their function in the uninjured brain. A series of recent in vivo imaging studies shows that microglia in their resting state are highly motile and actively survey their neuronal surroundings. Furthermore, new data suggest that microglia in their resting state are able to phagocytose unwanted synapses and in this way contribute to synaptic pruning and maturation during development. Coupled with their exquisite sensitivity to pathogenic stimuli, these data suggest that microglia form a link that couples changes in brain environment to changes in brain wiring. Here we discuss this hypothesis and propose a model for the role of microglia during development in sculpting brain connectivity.     

Physiological control of brain norepinephrine synthesis by brain tyrosine concentration

The intraperitoneal administration of tyrosine to rats causes proportional increases in brain tyrosine levels and in the accumulation of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylethyleneglycol-sulfate (MOPEG-SO₄) after probenecid. Brain tyrosine level after tyrosine administration or after the consumption of a single meal is also positively correlated with brain MOPEG-SO₄ accumulation in rats that do not receive probenecid but are subjected to cold stress. These observations extend our earlier finding that brain tyrosine level can affect the rates at which catecholaminergic neurons synthesize and turn over their transmitters.