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1.
NMDA(N-甲基-D-天氡氨酸)受体是离子型谷氨酸受体的一种亚型,在中枢神经系统的突触传递和突触可塑性调节中起着重要的作用。生物体内已经发现了三种NMDA受体亚基,通过基因的选择性剪切可产生多种亚单位。NMDA受体是一个具有多个结合位点的大分子复合物,其生理特性同异聚体通道的装配密切相关。NMDA受体的异常会导致一些认知功能的缺失,这为治疗性药物开发提供了靶点。  相似文献   

2.
谷氨酸性突触在痛觉和记忆中的突触和分子机制   总被引:5,自引:3,他引:2  
Zhuo M 《生理学报》2003,55(1):1-8
谷氨酸是哺乳动物脑中的兴奋性递质。中枢神经系统的谷氨酸性突触广泛参与痛觉传递,突触可塑性和递质的调节。谷氨酸的NMDA受体参与前脑相关的学习及功能。在这篇综述中,我们提出前脑的NMDA受体通过增强谷氨酸性突触传递导致长期性的炎痛。具有增强NMDA受体功能的小鼠会产生更多的慢性痛。NMDA NR2B受体抑制剂在未来可能被用来控制人类的慢性痛。  相似文献   

3.
N-甲基-D-天冬氨酸(NMDA)受体是离子型兴奋性谷氨酸受体的一种亚型,生物体内已发现了3种NMDA受体亚基,且通过选择性剪接至少存在7种亚型,形成具有功能的多结合位点的大分子复合物。NMDA受体在中枢神经系统的突触传递、突触可塑性、学习记忆等生理过程中发挥着重要作用,且NMDA受体的异常会导致-些精神疾病及认知功能的障碍。  相似文献   

4.
N-甲基-D-天氡氨酸受体的分子结构与生理功能   总被引:2,自引:0,他引:2  
NMDA(N-甲基-D-天氡氨酸)受体是离子型谷氨酸受体的一种亚型,在中枢神经系统的突触传递和突触可塑性调节中起着重要的作用。生物体内已经发现了三种NMDA受体亚基,通过基因的选择性剪切可产生多种亚单位。NMDA受体是一个具有多个结合位点的大分子复合物,其生理特性同异聚体通道的装配密切相关。NMDA受体的异常会导致一些认知功能的缺失,这为治疗性药物开发提供了靶点。  相似文献   

5.
Liauw J  Wang GD  Zhuo M 《生理学报》2003,55(4):373-380
谷氨酸性突触是哺乳动物神经系统的主要兴奋性突触。在正常条件下,大多数的突触反应是由谷氨酸的AMPA受体传递的。NMDA受体在静息电位下为镁离子抑制。在被激活时,NMDA受体主要参与突触的可塑性变化。但是,许多NMDA受体拮抗剂在全身或局部注射时能产生行为效应,提示NMDA受体可能参与静息状态的生理功能。此文中,我们在离体的前额扣带回脑片上进行电生理记录,发现NMDA受体参与前额扣带回的突触传递。在重复刺激或近于生理性温度时,NMDA受体传递的反应更为明显。本文直接显示了NMDA受体参与前额扣带回的突触传递,并提示NMDA受体在前额扣带回中起着调节神经元兴奋的重要作用。  相似文献   

6.
突触上的N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体与学习记忆以及细胞的存活有着密切关系,而定位于突触外的NMDA受体则参与了细胞死亡通路的激活.本文主要从突触NMDA受体的结构和功能出发,阐述突触上与突触外NMDA受体分布的原因,阐明其介导不同信号通路的具体分子机制及其在阿尔茨海默病(Alzheimer's disease,AD)中扮演的角色.最后,以突触外的NMDA受体为靶点,对AD疾病的治疗提出合理的展望,以期推动对该疾病的研究和治疗.  相似文献   

7.
NMDA受体是兴奋性氨基酸谷氨酸(Glu)的特异性受体,属配体门控离子通道,是由不同的亚单位组成.现已发现,NMDA受体至少存在7个亚单位(NR1,NR2A-D,NR3A-B),其中NR2B在7个亚单位中扮演非常重要的角色.近年来对NR2B研究表明,其在调控神经元突触的可塑性、学习与记忆以及治疗精神紊乱方面具有重要的意义.对近期有关NR2B亚单位的结构、功能特性及其表达与调控的研究进展做一综述.  相似文献   

8.
应激对大鼠海马Glu-NMDA受体通路的影响及锌的保护机制   总被引:1,自引:0,他引:1  
目的:探讨光-电应激对不同锌水平大鼠海马突触体谷氨酸摄取能力及海马N-甲基-D-门冬氨酸(NMDA)受体容量和亲和力的影响。方法:通过光-电刺激建立大鼠应激模型。观察实验动物旷场行为变化。以^3H-L-Glu作为放射配体进行海马NMDA受体结合反应,以放免法测定海马突触体谷氨酸摄取能力。结果:缺锌动物在旷场中活动较少,海马NMDA受体容量减少、海马突触体谷氨酸摄取能力显著下降;与相应非应激组比较,各应激组动物在旷场中停留时间延长,水平和垂直运动呈现减少趋势、海马NMDA受体容量均有增加趋势而海马突触体谷氨酸摄取能力有下降趋势,但以上各项指标仅缺锌应激组出现统计学差异。结论:光-电应激可导致大鼠在旷场中的行为异常,在缺锌情况下,实验动物出现更严重的异常反应。表明,海马NMDA受体容量及突触体谷氨酸摄取能力的变化参与了应激反应过程,推测其机制与海马Glu-NMDA受体通路的改变有关。  相似文献   

9.
成年小鼠前脑NMDA受体参与神经元的动作电位发放   总被引:2,自引:2,他引:0  
Wang GD  Zhuo M 《生理学报》2006,58(6):511-520
谷氨酸是中枢神经系统主要的快速兴奋性递质。AMPA受体和海人藻酸受体主要参与突触传递,而NMDA受体主要参与突触可塑性。基因操作的方法增强NMDA受体的功能,可以增强动物在正常生理状态下的学习能力,及在组织损伤情况下的反应敏感性。NMDA受体参与生理功能的主要机制是长时程增强(long—term potentiation,LTP)。我们的研究表明,NMDA受体不仅参与刺激前扣带皮层的第五层细胞或刺激白质诱导的突触反应,而且参与在胞体施加去极化跃阶电流诱导的动作电位的发放。钙一钙调蛋白敏感的腺苷酸环化酶1(adenylyl cyclase 1,AC1)和cAMP信号通路可能介导了这些反应。由于扣带皮层神经元在伤害性刺激和痛中发挥重要作用,我们的结果为前脑NMDA受体参与突触传递和动作电位发放,以及与前脑相关的行为,如感受伤害性刺激和痛,提供了一个新的机制。  相似文献   

10.
郑煜 《生理科学进展》1989,20(3):273-275
N-甲基-D-门冬氨酸(NMDA)受体是一种兴奋性氨基酸受体,广泛分布于许多脑区。该受体被激活后,突触后膜产生一长时程的兴奋性突触后电位,进而引起多种神经生物学效应或神经毒性作用。Ca~(2 )对于NMDA受体效应的产生具有重要意义。  相似文献   

11.
Several lines of evidence indicate that glutamate NMDA receptors are critically involved in long-term potentiation (LTP) and in certain forms of learning. It was previously demonstrated that memory formation of an inhibitory avoidance task in chick is specifically associated with an increase in the density of NMDA receptor in selected brain regions. Here we report on the effect of a one trial inhibitory avoidance training in rats, a hippocampal-dependent learning task, on the levels of different subunits of the glutamate NMDA receptor in synaptic plasma membranes (SPM) isolated from the hippocampus. Training rats on a one trial inhibitory avoidance task results in a rapid, transient and selective increase (+33 %, p < 0.05) in NMDA NR1 subunit expression in hippocampal SPM of rats sacrificed 30 min posttraining. No changes were observed at 0 or 120 min after training or in shocked animals in comparison to naive control rats. In addition, no training-associated increase in the levels of NMDA NR2A and NR2B or AMPA GluR 2/3 subunits was observed at any timepoint tested. In conclusion, the present findings support the hypothesis that alterations in expression of synaptic NMDA NR1 subunits in the hippocampus are specifically associated with memory formation of an inhibitory avoidance task and strongly suggest that hippocampal NMDA receptors are crucially involved in the neural mechanisms underlying certain forms of learning.These authors contributed equally to this work  相似文献   

12.
Ammonium, the end-product of nitrate-reduction, causes a marked increase in nitrate-dependent formation of nitrate reductase activity in pea shoot apices. The ammonium effect is mediated via a decrease in the rate of nitrate reductase decay. The increased stability of the enzyme in the presence of ammonium is indirect and depends upon protein synthesis. A regulatory role for ammonium-induced protein(s) is suggested.  相似文献   

13.
一株耐热纤维素酶产生菌的筛选及酶学特性   总被引:1,自引:0,他引:1  
从辽宁鞍山汤岗子温泉附近土样中分离得到能产生纤维素酶的真菌,通过形态观察和18S rRNA序列分析,该菌株为蒙昧的散囊菌纲(Uncultured Eurotiomycetes)。实验中对酶学性质进行了检验,测定得出该菌株产生的纤维素酶最适温度为65℃,在温度高达75℃仍能保持70%的酶活力,它的最适pH值为6.5,pH在5~8的范围内酶活力保持稳定。实验表明该菌株所产纤维素酶具有较高的pH稳定性和温度稳定性,值得对该酶进行进一步的研究。  相似文献   

14.
Incubation of 5-d-old maize seedlings in the half-strength Hoagland's nutrient solution containing 10 mM KNO3 with FeCl3 or FeSO4 (0.5 or 2.0 mM) caused a significant increase in nitrate reductase (NR) activity and slightly increased total protein content in root, shoot and scutellum. In case of root, NADPH:NR activity was inhibited contrary to the NADH:NR activity. In spite of NR activity, nitrate uptake was inhibited from 13 to 37 % by the iron. The results presented demonstrate an isoform specific, organ specific, and to some extent salt specific responses of NR to iron.  相似文献   

15.
We have investigated the role of N-methyl-d-aspartate receptors (NMDARs) and γ-aminobutyric acid receptors type A (GABAARs) at an early stage of P19 neuronal differentiation. The subunit expression was profiled in 24-hour intervals with RT-PCR and functionality of the receptors was verified via fluo-3 imaging of Ca2+ dynamics in the immature P19 neurons showing that both NMDA and GABA excite neuronal bodies, but only polyamine-site sensitive NMDAR stimulation leads to enhanced Ca2+ signaling in the growth cones. Inhibition of NR1/NR2B NMDARs by 1 μM ifenprodil severely impaired P19 neurite extension and fasciculation, and this negative effect was fully reversible by polyamine addition. In contrast, GABAAR antagonism by a high dose of 200 μM bicuculline had no observable effect on P19 neuronal differentiation and fasciculation. Except for the differential NMDAR and GABAAR profiles of Ca2+ signaling within the immature P19 neurons, we have also shown that inhibition of NR1/NR2B NMDARs strongly decreased mRNA level of NCAM-180, which has been previously implicated as a regulator of neuronal growth cone protrusion and neurite extension. Our data thus suggest a critical role of NR1/NR2B NMDARs during the process of neuritogenesis and fasciculation of P19 neurons via differential control of local growth cone Ca2+ surges and NCAM-180 signaling.  相似文献   

16.
The present study characterized the effects of withdrawal from cocaine on the expression of NMDA receptor subunits (NR1, NR2B) and neuronal nitric oxide synthase. FosB induction was measured to confirm that repeated cocaine exposure influenced protein expression, as previously reported. Administration of cocaine followed by 24 h, 72 h, or 14 days of withdrawal resulted in alterations of NR1 and NR2B subunits and neuronal nitric oxide synthase expression as measured by immunohistochemical labeling of rat brain sections. Optical density analyses revealed significant up-regulation of NR1 in the ventral tegmental area at 72 h and 14 days of withdrawal. Structure-specific and withdrawal time-dependent alterations in NR2B expression were also found. After 24 h of withdrawal, cocaine-induced decreases in NR2B expression were observed in the nucleus accumbens shell, whereas increases in NR2B expression were found in medial cortical areas. Two weeks of withdrawal from cocaine caused an approximately 50% increase in NR2B subunit expression in regions of the cortex, neostriatum, and nucleus accumbens. In contrast, cocaine-induced up-regulation of neuronal nitric oxide synthase was transient and evident in cortical areas only at 24 h after the last drug injection. The results suggest that region-specific changes in interactions among proteins associated with the NMDA receptor complex may underlie neuronal adaptations following repeated cocaine administration.  相似文献   

17.
Animals must recognize and remember conspecifics and potential mates, and distinguish these animals from potential heterospecific competitors and predators. Despite its necessity, aged animals are known to exhibit impaired social recognition memory. As the brain ages, the ratio of NR2A:NR2B in the brain increases over time and has been postulated to underlie the cognitive decline observed during the aging process. Here, we test the hypothesis that an increased NR2A:NR2B subunit ratio underlies long‐term social recognition memory. Using transgenic overexpression of NR2A in the forebrain regions, we investigated the ability of these mice to learn and remember male and female conspecifics, mice of another strain and animals of another rodent species, the rat. Furthermore, due to the importance of olfaction in social recognition, we tested the olfactory memory in the NR2A transgenic mice. Our series of behavioral experiments revealed significant impairments in the NR2A transgenic mice in long‐term social memory of both male and female conspecifics. Additionally, the NR2A transgenic mice are unable to recognize mice of another strain or rats. The NR2A transgenic mice also exhibited long‐term memory impairments in the olfactory recognition task. Taken together, our results provide evidence that an increased NR2A:NR2B ratio in the forebrain leads to reduced long‐term memory function, including the ethologically important memories such as social recognition and olfactory memory .  相似文献   

18.
NMDA receptors play essential roles in the physiology and pathophysiology of the striatum, a brain nucleus involved in motor control and reward-motivated behaviors. NMDA receptors are composed of NR1 and NR2A–D subunits. Functional properties of NMDA receptors are determined by the type of NR2 subunit they contain. In this study, we have examined the involvement of NR2B and NR2A in the modulatory effect of NMDA on glutamatergic and dopaminergic synaptic transmission in the striatum. We found that bath application of NMDA decreased the amplitude of the field excitatory post-synaptic potential/population spike (fEPSP/PS) measured in corticostriatal mouse brain slices. This depression was not affected by the NR2B-selective antagonists Ifenprodil and Ro 25-6981, but was abolished by the NR2A antagonist NVP-AAM077. Activation of corticostriatal neurons by NMDA did not contribute to synaptic depression because similar results were obtained in decorticated striatal slices. Synaptic depression was not dependent on GABA release because the GABAA receptor antagonist bicuculline did not affect NMDA-induced decrease of the fEPSP/PS. NMDA also depressed evoked-dopamine release through NR2A- but not NR2B-containing NMDA receptors. Our results identify an important role for NR2A-containing NMDA receptors intrinsic to the striatum in regulating glutamatergic synaptic transmission and evoked-dopamine release.  相似文献   

19.
Chronic ethanol treatment of cultured neurons from various brain areas has been found to increase NMDA receptor function and to alter the levels of some NMDA receptor subunit proteins. Because the cultured neurons are exposed to ethanol during a period when the NMDA receptor is undergoing developmental changes in subunit expression, we wished to determine whether ethanol treatment alters this developmental pattern. We found that 3 days of treatment of cerebellar granule neurons with ethanol, which was previously reported to increase NMDA receptor function, resulted in a delay in the 'developmental switch' of the NR2A and NR2B subunits, i.e. the developmental decrease in NR2B and increase in NR2A protein expression. As a result, the level of NR2B was higher, and that of NR2A was lower, in the ethanol-treated cells than in control cells. Cross-linking experiments showed that the changes in total receptor subunit proteins levels were reflected in cell-surface expressed proteins, indicating changes in the amount of functional receptors. These results were confirmed by a higher potency of glycine at the NMDA receptor in the ethanol-treated cells, as determined by NMDA/glycine-induced increases in intracellular Ca(2+). The results suggest that the mechanism by which ethanol alters NMDA receptor expression in cultured neurons, where receptors are undergoing development, differs from the mechanism of ethanol's effect on NMDA receptors in adult brain. Changes in the proportion of NR2A and NR2B subunits may contribute to effects of ethanol on neuronal development.  相似文献   

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