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1.
Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils 总被引：1，自引：0，他引：1
beta-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta-amyloid Abeta42 fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can accelerate NFT formation in vivo. 相似文献
2.
Roberson ED Scearce-Levie K Palop JJ Yan F Cheng IH Wu T Gerstein H Yu GQ Mucke L 《Science (New York, N.Y.)》2007,316(5825):750-754
Many potential treatments for Alzheimer's disease target amyloid-beta peptides (Abeta), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Abeta-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Abeta levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions. 相似文献
3.
Suicide transport: destruction of neurons by retrograde transport of ricin, abrin, and modeccin 总被引：5，自引：0，他引：5
Certain toxic lectins, including ricin, are retrogradely transported along neuronal processes to the cell body where they inactivate ribosomes, resulting in neuronal death. This process of "suicide transport" suggests a powerful new experimental strategy for solving neurobiological problems. 相似文献
4.
[目的]测定蜡蚧轮枝菌MZ041024菌株对南瓜实蝇各虫态的室内毒力,为利用蜡蚧轮枝菌进行生物防治提供理论依据.[方法]以南瓜实蝇的幼虫、成虫和蛹为目标昆虫,利用3.0×104、3.0×105、3.0×106、3.0×107、3.0×108个孢子/mL 5个浓度的蜡蚧轮枝菌MZ041024菌株分生孢子液对其进行室内毒力测定.[结果]蜡蚧轮枝菌MZ041024菌株在室内对南瓜实蝇幼虫、成虫和蛹具有较强的毒力,其中在3.0×108个孢子/mL浓度下南瓜实蝇各虫态的死亡率均达最高,幼虫的校正死亡率为（80.1 1±1.32）％、LT50为4.513±0.359 d、第9d的LC50为（2.907±0.495）×104个孢子、mL;成虫的校正死亡率为（87.78±1.11）％、LT50为3.585±0.385 d、第9d的LC50为（2.366±0.579）×104个孢子/mL;蛹的校正死亡率为（81.11±2.94）％、LT50为4.152±0.289 d,第9d的LC50为（2.495±0.375）× 104个孢子/mL.[结论]蜡蚧轮枝菌MZ041024菌株在室内对南瓜实蝇各虫态均有一定毒力,对各虫态毒力大小表现为成虫＞蛹＞幼虫;高浓度的蜡蚧轮枝菌分生孢子液对南瓜实蝇的防治效果优于低浓度的防治效果. 相似文献
5.
唐菱 《湖南农业大学学报(自然科学版)》2005,(2)
结合解剖学和功能性神经影像研究,通过语言中单个生词在大脑中的语义处理的分析,对国外一百多年以来的语言认知模式进行概括、综述,介绍大脑中语言的认知模式:19世纪解剖学和认知(词语视听处理)相结合的神经学模式;20世纪强调实现阅读的两种不同途径的认知模式。根据功能性影像研究成果讨论:19 世纪神经学家的观点(大脑的左后上颞皮层(IPSTC)及后下前皮层(PIFC)管辖词语的视听活动)和被其所忽视、20 世纪认知科学家提出的阅读第二途径(后下颞皮层(LPIC)对词语进行修复活动)看法的利弊。人们曾以为角回(AG 相似文献
6.
Tan J Town T Paris D Mori T Suo Z Crawford F Mattson MP Flavell RA Mullan M 《Science (New York, N.Y.)》1999,286(5448):2352-2355
Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis. 相似文献
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8.
The brain connection: the corpus callosum is larger in left-handers 总被引：13，自引：0，他引：13
S F Witelson 《Science (New York, N.Y.)》1985,229(4714):665-668
The size of the midsagittal area of the human corpus callosum obtained from postmortem measurement varied with tested hand preference. The corpus callosum, the main fiber tract connecting the two cerebral hemispheres, was larger by about 0.75 square centimeter, or 11 percent, in left-handed and ambidextrous people than in those with consistent right-hand preference. The difference was present in both the anterior and posterior halves, but not in the region of the splenium itself. This callosal morphology, which varied with hand preference, may also be related to individual differences in the pattern of hemispheric functional specialization. The greater bihemispheric representation of cognitive functions in left- and mixed-handers may be associated with greater anatomical connection between the hemispheres. The naturally occurring regressive events in neurogenesis, such as neuronal cell death and axonal elimination, may be factors in the individual differences in brain morphology and in functional lateralization. Specifically, right-handers may be those with more extensive early elimination of neural components. 相似文献
9.
Gu Z Kaul M Yan B Kridel SJ Cui J Strongin A Smith JW Liddington RC Lipton SA 《Science (New York, N.Y.)》2002,297(5584):1186-1190
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass spectrometry identified the active derivative of MMP-9, both in vitro and in vivo, as a stable sulfinic or sulfonic acid, whose formation was triggered by S-nitrosylation. These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity. 相似文献
10.
A68: a major subunit of paired helical filaments and derivatized forms of normal Tau 总被引：107，自引：0，他引：107
Putative Alzheimer disease (AD)-specific proteins (A68) were purified to homogeneity and shown to be major subunits of one form of paired helical filaments (PHFs). The amino acid sequence and immunological data indicate that the backbone of A68 is indistinguishable from that of the protein tau (tau), but A68 could be distinguished from normal human tau by the degree to which A68 was phosphorylated and by the specific residues in A68 that served as phosphate acceptors. The larger apparent relative molecular mass (Mr) of A68, compared to normal human tau, was attributed to abnormal phosphorylation of A68 because enzymatic dephosphorylation of A68 reduced its Mr to close to that of normal tau. Moreover, the LysSerProVal motif in normal human tau appeared to be an abnormal phosphorylation site in A68 because the Ser in this motif was a phosphate acceptor site in A68, but not in normal human tau. Thus, the major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68. 相似文献
11.
Adult emergence at the end of metamorphosis in the moth Manduca sexta is followed by the death of abdominal interneurons and motoneurons. Abdominal ganglia removed from insects before this period of naturally occurring cell death and maintained in vitro showed neuronal death confined to the same cells that normally die in vivo. Addition of physiological levels of the steroid 20-hydroxyecdysone to the culture system prevented the selective death of these motoneurons. 相似文献
12.
Delayed transneuronal death of substantia nigra neurons prevented by gamma-aminobutyric acid agonist 总被引：7，自引：0，他引：7
In an investigation of the mechanism by which brain lesions result in delayed degeneration of neurons remote from the site of injury, neurons within the caudate nucleus of rats were destroyed by local injection of the excitotoxin ibotenic acid. Treatment resulted in the rapid degeneration of the striatonigral pathway including projections containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and delayed transneuronal death of neurons in the substantia nigra pars reticulata. The distribution of nigral cell loss corresponded to the loss of GABAergic terminals. Neuronal death was prevented by long-term intraventricular infusion of the GABA agonist muscimol. Delayed transneuronal degeneration may be produced by neuronal disinhibition consequent to loss of inhibitory inputs. Replacement of inhibitory transmitters by suitable drugs may prevent some forms of delayed neuronal death. 相似文献
13.
Human recombinant tissue plasminogen activator (tPA) may benefit ischemic stroke patients by dissolving clots. However, independent of thrombolysis, tPA may also have deleterious effects on neurons by promoting excitotoxicity. Zinc neurotoxicity has been shown to be an additional key mechanism in brain injuries. Hence, if tPA affects zinc neurotoxicity, this may provide additional insights into its effect on neuronal death. Independent of its proteolytic action, tPA markedly attenuated zinc-induced cell death in cortical culture, and, when injected into cerebrospinal fluid, also reduced kainate seizure-induced hippocampal neuronal death in adult rats. 相似文献
14.
The fluorescence decay time (tau) was 2 to 5 nanoseconds for proteins and 4 to 5 nanoseconds for flavin, pyridine nucleotide, and vitamin B(6)coenzymes; tau varied widely in 48 compounds measured in water. Altholugh reported values of tau for a few of the soluttions studied were in excellenlt agreement. previously "calculated" lifetimes, in severall instances, are apparently erroneous. Nonexponential decay was detectable with our "nanosecond-flash" apparatus, a modification of the first commercially aavilable unit for determination of tau. 相似文献
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16.
Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein and kinesin motility, we conducted single-molecule studies of motor proteins moving along tau-decorated microtubules. Dynein tended to reverse direction, whereas kinesin tended to detach at patches of bound tau. Kinesin was inhibited at about a tenth of the tau concentration that inhibited dynein, and the microtubule-binding domain of tau was sufficient to inhibit motor activity. The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport. 相似文献
17.
The primary structure and heterogeneity of tau protein from mouse brain 总被引：74，自引：0，他引：74
Tau protein is a family of microtubule binding proteins, heterogeneous in molecular weight, that are induced during neurite outgrowth and are found prominently in neurofibrillary tangles in Alzheimer's disease. The predicted amino acid sequences of two forms of tau protein from mouse brain were determined from complementary DNA clones. These forms are identical in their amino-terminal sequences but differ in their carboxyl-terminal domains. Both proteins contain repeated sequences that may be tubulin binding sites. The sequence suggests that tau is an elongated molecule with no extensive alpha-helical or beta-sheet domains. These complementary DNAs should enable the study of various functional domains of tau and the study of tau expression in normal and pathological states. 相似文献
18.
Regressive events in neurogenesis 总被引：71，自引：0，他引：71
The development of most regions of the vertebrate nervous system includes a distinct phase of neuronal degeneration during which a substantial proportion of the neurons initially generated die. This degeneration primarily adjusts the magnitude of each neuronal population to the size or functional needs of its projection field, but in the process it seems also to eliminate many neurons whose axons have grown to either the wrong target or an inappropriate region within the target area. In addition, many connections that are initially formed are later eliminated without the death of the parent cell. In most cases such process elimination results in the removal of terminal axonal branches and hence serves as a mechanism to "fine-tune" neuronal wiring. However, there are now also several examples of the large-scale elimination of early-formed pathways as a result of the selective degeneration of long axon collaterals. Thus, far from being relatively minor aspects of neural development, these regressive phenomena are now recognized as playing a major role in determining the form of the mature nervous system. 相似文献
19.
Mental rotation of the neuronal population vector 总被引：19，自引：0，他引：19
A P Georgopoulos J T Lurito M Petrides A B Schwartz J T Massey 《Science (New York, N.Y.)》1989,243(4888):234-236
A rhesus monkey was trained to move its arm in a direction that was perpendicular to and counterclockwise from the direction of a target light that changed in position from trial to trial. Solution of this problem was hypothesized to involve the creation and mental rotation of an imagined movement vector from the direction of the light to the direction of the movement. This hypothesis was tested directly by recording the activity of cells in the motor cortex during performance of the task and computing the neuronal population vector in successive time intervals during the reaction time. The population vector rotated gradually counterclockwise from the direction of the light to the direction of the movement at an average rate of 732 degrees per second. These results provide direct, neural evidence for the mental rotation hypothesis and indicate that the neuronal population vector is a useful tool for "reading out" and identifying cognitive operations of neuronal ensembles. 相似文献
20.
Repeated administration of morphine in increasing doses delayed normal cell death in the ciliary ganglion of the chick embryo; the effect was completely blocked by naloxone. Survival of spinal motoneurons was not affected. Morphine also inhibited potassium-stimulated synthesis of acetylcholine in ganglion cells cultured with muscle, suggesting that morphine can influence neurotransmission. Morphine's effect on cell death may be due to an inhibition of transmission at the neuromuscular junction, but opiates may also directly affect cell death. Although it is now known whether the endogenous opiates in the ciliary ganglion influence neuronal survival during embryogenesis, exogenous opiates can affect normal cell death in the autonomic nervous system. 相似文献