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1.
《Clinical therapeutics》2019,41(5):836-847
PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies. 相似文献
2.
《Clinical neurophysiology》2020,131(1):213-224
ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology. 相似文献
3.
采用~(125)I 标记小鼠抗人IL—2受体(P55)的抗Tac(CD_(25))单克隆抗体,成功地建立了人IL—2受体的免疫放射分析法,动态观察了人外周血淋巴细胞经PHA 刺激24、48和72h 后IL—2受体表达的时间曲线,通过Scatchard 作图分析表明~(125)I—抗Tac 单克隆抗体与PHA 活化的上述三个时间点的T 淋巴细胞的最大结合容量(B_(max))分别为43000位点/细胞、54000位点/细胞和61000位点/细胞。本研究为临床IL—2受体检测提供一种简便的免疫放射测定法。 相似文献
4.
The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one. 相似文献
5.
John F. Scrymgeour-Wedderburn Carolyn A. Reith Keith T. Sillar 《The European journal of neuroscience》1997,9(7):1473-1482
The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT1, a selective 5HT1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg2+, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg2+ block. When the membrane potential was depolarized by ~20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg2+ through activation of receptors with 5HT1a-like pharmacology. 相似文献
6.
There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca2+ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley-Liss, Inc. 相似文献
7.
Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex. 总被引:9,自引:0,他引:9
C Cepeda Z Radisavljevic W Peacock M S Levine N A Buchwald 《Synapse (New York, N.Y.)》1992,11(4):330-341
The responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N-methyl-D-aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy. 相似文献
8.
C. M. A. Pennartz R. F. Ameerun H. J. Groenewegen F. H. Lopes da Silva 《The European journal of neuroscience》1993,5(2):107-117
Extra- and intracellular recordings in slices were used to examine what types of synaptic plasticity can be found in the core of the nucleus accumbens, and how these forms of plasticity may be modulated by dopamine. Stimulus electrodes were placed at the rostral border of the nucleus accumbens in order to excite primarily infralimbic and prelimbic afferents, as was confirmed by injections of the retrograde tracer fluoro-gold. In extracellular recordings, tetanization induced long-term potentiation (LTP) of the population spike in 20 out of 53 slices. The presynaptic compound action potential did not change following LTP induction. For the intracellularly recorded excitatory postsynaptic potential, three types of synaptic plasticity were noted: long-term potentiation (16 out of 54 cells), decremental potentiation (eight cells) and long-term depression (LTD; six cells). No correlation was found between the occurrence of potentiation or depression and various parameters of the tetanic depolarization (e.g. peak voltage, integral under the curve). The N -methyl- d -aspartate receptor antagonist d (–)-2-amino-5-phosphonopentanoic acid (50 μM; d -AP5) reduced, but did not completely prevent, the induction of LTP. The incidence of LTD was not markedly affected by d -AP5. No difference in LTP was found when comparing slices bathed in dopamine (10 μM) and controls. Likewise, slices treated with a mixture of the D1 receptor antagonist Sch 23390 (1 μM) and the D2 antagonist S (–)-sulpiride (1 μM) generated a similar amount of LTP as controls. In conclusion, both LTP and LTD can be induced in a key structure of the limbic-innervated basal ganglia. LTP in the nucleus accumbens strongly depends on N -methyl- d -aspartate receptor activity, but is not significantly affected by dopamine. 相似文献
9.
高原低氧对大鼠学习记忆影响的实验研究 总被引:4,自引:1,他引:3
目的:研究高原低氧环境对大鼠学习记忆的影响。方法:利用新生大鼠低氧模型和胎鼠低氧模型,采用爬杆实验和Morris水迷宫实验进行检测.结果:爬杆实验中习得的速度减慢,消退速度加快。Morris水迷宫实验中逃避潜伏期延长,撤除平台后跨越平台次数减少。结论:高原低氧环境下大鼠的学习记忆能力受到抑制,可能与长期低氧后海马NMDA受体数量和功能的下降有关。 相似文献
10.
目的研究加兰他敏对阿尔茨海默病(AD)大鼠认知功能的影响及NMDA受体在其中的作用。方法雄性SD大鼠65只,随机分为假手术、链脲菌素(STZ)组,加兰他敏、MK-801和犬尿烯酸3个治疗组。侧脑室注射STZ制备大鼠AD模型,水迷宫试验测定大鼠的学习记忆能力。3个治疗组分别给予加兰他敏、MK-801 加兰他敏、犬尿烯酸 加兰他敏,共6周。结果术后第10天各组潜伏期明显延长,过平台次数明显减少,差异均无统计学意义。治疗6周后加兰他敏组潜伏期缩短,过平台次数增加,与STZ组比较,有显著差异,而MK-801和犬尿烯酸组潜伏期和过平台次数与STZ组比较,无明显差异。结论加兰他敏对AD大鼠的认知功能具有明显的改善作用,而应用NMDA受体阻断剂后其治疗作用消失。说明NMDA受体介导了加兰他敏对AD大鼠认知功能的改善。 相似文献