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抑郁症相关受体作用机制的研究进展 总被引:3,自引:2,他引:1
抑郁症是一种病因很复杂的疾病,其发病机制与受体有着密切的关系。本文简要介绍了几种与抑郁症相关的受体,阐述了其生理功能及在抑郁症发病机制中的作用。 相似文献
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左归降糖解郁方对糖尿病并发抑郁症大鼠行为学及认知功能的影响 总被引:2,自引:2,他引:0
目的 研究左归降糖解郁方对糖尿病并发抑郁症大鼠行为学及认知功能的影响。方法 建立糖尿病并发抑郁症动物模型并随机分为6组,模型组、二甲双胍(0.18 g·kg-1)+盐酸氟西汀(1.8 mg·kg-1)组(阳性药组)、左归降糖解郁方高、中、低剂量(20.53,10.26,5.13 g·kg-1)组,并设正常对照组。给药42 d后,进行开野和Morris水迷宫行为学评价,采用ELISA法测定各组大鼠血浆促肾上腺激素释放激素(corticotropin releasing hormone,CRH)、促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)含量。结果 与正常对照组比较,模型组大鼠开野实验中活动总数明显减少(P<0.01),Morris水迷宫实验中逃避潜伏期明显延长(P<0.05或P<0.01),空间探索时间明显缩短(P<0.05);血浆CRH、ACTH含量显著升高(P<0.05或P<0.01)。与模型组比较,给予左归降糖解郁方高剂量后,模型大鼠活动次数增多(P<0.05),学习记忆能力得到一定程度恢复,血浆CRH、ACTH水平明显降低(P<0.05)。结论 左归降糖解郁方可改善糖尿病并发抑郁症模型大鼠的抑郁行为及认知障碍,可能与其降低CRH和ACTH水平,缓解HPA轴亢进有关。 相似文献
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促肾上腺皮质激素释放因子(CRF)主要通过CRF1受体参与调节下丘脑-垂体-肾上腺轴应激反应.研究表明CRF过度分泌可能是抑郁症等情感障碍的病因机制之一.CRF1受体作为新一代潜在抑郁药物靶点正逐渐成为一个充满希望的研究热点.本文对近年来国内外有关CRF1受体拮抗剂的文献和专利进行了分析和归纳,主要介绍了CRF1受体拮抗剂的开发现状及其构效关系. 相似文献
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神经激肽中P物质是中枢神经系统最重要的神经递质之一,通过与其受体,如神经激肽1受体(NK1R)结合在多种疾病的病理过程中发挥作用。NK1R拮抗剂近年来在临床上应用广泛,不仅能够缓解抑郁、焦虑的症状,而且对抑郁症、焦虑症和化疗引起的恶心、呕吐具有很好的疗效。本文就近年来NK1R拮抗剂的研究进展进行综述。 相似文献
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谷氨酸-谷氨酰胺循环是大脑中谷氨酸合成与代谢的主要途径,谷氨酸作为兴奋性神经递质调节大脑生理功能。近年来,大量研究表明抑郁症的发病过程与谷氨酸-谷氨酰胺循环障碍存在重要联系。基于此,本文综述归纳了谷氨酸生理作用、谷氨酸-谷氨酰胺循环过程、抑郁症中循环障碍表现以及靶向谷氨酸能系统药物在抑郁症中的研究现状,以期为后续研究提供参考依据。 相似文献
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吗啡依赖及戒断大鼠糖皮质激素及其受体mRNA表达水平的改变 总被引:5,自引:0,他引:5
目的:研究慢性吗啡处理和吗啡戒断对大鼠血清中ACTH及其受体mRNA表达水平的影响。方法:利用放射免疫法测定吗啡依赖及戒断大鼠血清中ACTH及皮质醇的浓度;利用核酸分子杂交技术研究下丘脑糖皮质激素受体(GR)基因表达的改变情况。结果:(1)吗啡依赖组大鼠血清中ACTH及皮质醇的浓度明显低于对照组;戒断d1大鼠血清ACTH浓度仍明显低于对照组(P<0.01),但血清皮质醇的浓度则明显高于对照组(P<0.01);戒断d7大鼠血清ACTH浓度与对照组比较,无显著性差异(P>0.05),而血清皮质醇的浓度仍略高于对照组(P<0.05);(2)吗啡依赖组大鼠下丘脑GR基因表达水平下降(P<0.05),戒断组大鼠GR的基因表达均高于对照组,但无显著性差异(P>0.05)。结论:吗啡类物质的长期使用可以对下丘脑-垂体-肾上腺轴的激素分泌功能及GR的基因表达产生明显的抑制作用。 相似文献
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《Expert opinion on therapeutic targets》2013,17(4):651-684
The treatment of mood disorders has been the subject of intense study for more than half a century and has resulted in the discovery and availability of a number of compounds that have seen tremendous success in the management of major depression and anxiety-related disorders. In spite of this success, these drugs have not provided a complete therapeutic solution for all patients and this has revitalised the need for a greater understanding of the underlying molecular mechanisms and targets involved in these disorders. Elucidation of these novel targets will enable the development of a better class of compounds which could benefit a greater majority of the patient population and be devoid of the current side effect liabilities. Towards that end, this review examines, in detail, the prospect of one such target, the corticotropin-releasing factor system, as having an enhanced therapeutic profile with the potential of a broader range of efficacy with reduced side effect liabilities. 相似文献
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Group I metabotropic glutamate receptors (mGluRs) are expressed by many interneurons of the hippocampus. Although they have been implicated in short- and long-term synaptic plasticity of glutamatergic transmission, their roles in modulating transmission to interneurons are incompletely understood. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) acutely depressed transmission at synapses in the feed-forward inhibitory pathway made by Schaffer collaterals on interneurons in the rat hippocampal CA1 sub-field. DHPG elicited a qualitatively similar depression at synapses made by pyramidal neuron axon collaterals on interneurons in the feedback circuit in stratum oriens. Selective blockers revealed a link from mGluR1 to reversible, and mGluR5 to long-lasting, depression. The acute DHPG-induced depression was consistently accompanied by an elevation in paired-pulse ratio, implying a presynaptic decrease in release probability. However, it was also attenuated by blocking G-protein and Ca2+ signalling within the postsynaptic neuron, arguing for a retrograde signalling cascade. The DHPG-evoked depression was unaffected by antagonists of CB1 and GABAB receptors but was occluded when presynaptic P/Q-type Ca2+ channels were blocked. Finally, high-frequency stimulation delivered to an independent conditioning pathway evoked a heterosynaptic reversible depression, which was sensitive to group I mGluR antagonists. Group I mGluRs thus powerfully modulate synaptic excitation of hippocampal interneurons and mediate inter-synaptic cross-talk.This article is part of a Special Issue entitled ‘Synaptic Plasticity & Interneurons’. 相似文献
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Imidazoline receptors (IR), a novel family of non-adrenergic receptors, are present in brain, especially the limbic system, and platelets among other organs. Their functions include central mediation of blood pressure control and possibly modulation of affective symptomatology. Studies of unipolar depressed patients have revealed consistent up-regulation of the I(1) subtype on the platelet. Treatment with cyclic antidepressants is accompanied by down-regulation in responders. Treatment with the non-cyclic bupropion produced similar findings. Studies of human post-mortem brain show changes in depressed subjects but the protein fragments assessed are of different molecular weights than in the platelet. Plasma agmatine is believed to be a putative endogenous ligand for I receptors. Thus, IR may be useful state markers of affective disorders. Copyright 2001 John Wiley & Sons, Ltd. 相似文献
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抑郁症是一种常见的精神疾病,其发病率在不断上升,而且难以治愈。目前抑郁症的治疗药物主要包括:三环类抗抑郁药、单胺氧化酶抑制剂和可逆性选择性单胺氧化酶抑制药、选择性5-HT再摄取抑制剂、选择性NE再摄取抑制剂、5-HT及NA再摄取抑制药、NA及DA再摄取抑制药等。本文就抗抑郁药及特殊情况下抑郁症的药物治疗进展作一综述。 相似文献
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Sabatino Maione Enza Palazzo Vito de Novellis Luigi Stella Juan Leyva Francesco Rossi 《Naunyn-Schmiedeberg's archives of pharmacology》1998,358(4):411-417
The role of metabotropic (mGluRs) and N-methyl-D-aspartate (NMDA) glutamate receptors on 5-hydroxytryptamine (5-HT) release
has been studied in rat periaqueductal gray (PAG) matter by using in vivo microdialysis. (1S,3R)-aminocyclopentane-1,3-dicarboxylic
acid [(1S,3R)-ACPD; 0.5 or 1 mM], a group I/group II mGluRs agonist, increased the dialysate 5-HT concentration. (2S)-α-ethylglutamic
acid (EGlu; 1 mM), an antagonist of group II mGluRs, but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 mM), an antagonist
of group I mGluRs, antagonized the 1S,3R-ACPD-induced effect. (S)-3,5-dihydroxyphenylglycine (DHPG; 0.5 and 1 mM), an agonist
of group I mGluRs, did not modify dialysate 5-HT. (2S, 3S, 4S)-α-(carboxycyclopropyl)-glycine (L-CCG-I; 0.5 and 1 mM), an
agonist of group II mGluRs, increased extracellular 5-HT. This effect was antagonized by EGlu. Similarly, L-serine-O-phosphate
(L-SOP; 1 and 10 mM), an agonist of group III mGluRs, increased extracellular 5-HT and this effect was antagonized by (RS)-α-methylserine
O-phosphate (M-SOP; 1 mM), an antagonist of group III mGluRs. Out of the several N-methyl-D-aspartate concentrations used
(NMDA; 10, 50, 100, 500 and 1000 μM) only the 50 μM infusion significantly decreased dialysate 5-HT. The GABAA receptor agonist, bicuculline (30 μM), increased 5-HT release on its own and antagonized the decrease caused by the opiate
antagonist, naloxone (2 mM), as well as the increases caused by CCG-I or L-SOP. These data show that stimulation of PAG’s
group II/group III mGluRs increases 5-HT release, while stimulation of NMDA glutamate receptors may decrease it. We speculate
that glutamate does not modulate 5-HT release in the PAG directly, but via activation of tonically active GABAergic interneurons.
Received: 15 January 1998 / Accepted: 22 July 1998 相似文献
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Activation of NR2B-containing NMDA receptors is not required for NMDA receptor-dependent long-term depression 总被引:1,自引:0,他引:1
The triggering of both NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) in the CA1 region of the hippocampus requires a rise in postsynaptic calcium. A prominent hypothesis has been that the detailed properties of this postsynaptic calcium signal dictate whether LTP or LTD is generated by a given pattern of synaptic activity. Recently, however, evidence has been presented that the subunit composition of the NMDA receptor (NMDAR) determines whether a synapse undergoes LTP or LTD with NR2A-containing NMDARs triggering LTP and NR2B-containing NMDARs triggering LTD. In the present study, the role of NR2B-containing synaptic NMDARs in the induction of LTD in CA1 pyramidal cells has been studied using the selective NR2B antagonists, ifenprodil and Ro25-6981. While both antagonists reduced NMDAR-mediated synaptic currents, neither prevented induction of LTD. These results demonstrate that activation of NR2B-containing NMDARs is not an absolute requirement for the induction of LTD in the hippocampus. 相似文献
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抑郁症是严重危害人类身心健康的常见病,随着"生物–心理–社会"的现代医学模式转变,发现其常与其他重大疾病如糖尿病、高血脂、心脏病、高血压等代谢综合征组分并存,合并疾病发病率高且预后不良,以及造成对家庭和社会的高负担,关于其发病机制和防治措施的研究方兴未艾。抑郁症和代谢性疾病的发病可能存在一定共病基础和因果关系,旨在重点探讨脂质代谢紊乱和血管内皮功能障碍在抑郁症合并代谢性疾病的病理发展和共病机制中的作用,同时归纳总结现有治疗药物对脂质代谢异常和内皮功能障碍的影响,为临床用药的优选及其共病患者的治疗方式提供综述基础。 相似文献
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抑郁症严重危害人类身心健康,世界卫生组织预测:2020年抑郁症将成为非正常死亡和残疾的第二大原因。目前临床上大多使用三环类抗抑郁药(TCA)、四环类抗抑郁药、选择性5-HT再摄取抑制药等来治疗抑郁症,但长期应用这类药物易产生耐药性,不良反应明显,且这种通过单一成分阻断特定单一靶点的药物,对于涉及体内多个系统的生物学异常往往难以达到治疗效果。中药组方通过其所包含的多组分能同时调节多靶点、调节疾病网络的多个环节,在获得较高疗效的同时可降低化学药单靶点引起的毒副作用,且目前国内外对一些传统中药抗抑郁作用机制的研究报道也日渐增多,主要集中在神经递质水平释放、海马脑源性神经营养因子(BDNF)表达及细胞因子等方面。此外,最新的研究认为肠道菌群可能参与了从情感性疾病到神经系统疾病的发生发展。综述近年来中药抗抑郁神经保护作用的机制研究进展,以期为抑郁症发病机制探讨及抗抑郁药物研究提供借鉴和指导。 相似文献
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Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy (EM), and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a β sheet of aminoterminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state. 相似文献