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Differential Expression of mglur2 in the Developing Cerebral Cortex of the Mouse

Journal of Biomedical Science and Engineering 2014年第13期7卷 1030-1037页

作者： Pooja S. Venkatadri Charles C. Lee Department of Comparative Biomedical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge USA

Glutamatergic synaptic transmission is an essential component of neural circuits in the central nervous system. Glutamate exerts its effects by binding to various types of glutamate receptors, which are found distributed on neurons throughout the central nervous system. These receptors are broadly classified into two main groups, ionotropic glutamate receptors (iGluRs) and metabo-tropic glutamate receptors (mglurs). Unlike iGluRs, the mglurs are G-protein coupled receptors that exert their effects on postsynaptic membrane conductance indirectly through the downstream modification of ion channels. A subtype of mglurs, the Group II mglurs, are particularly interesting since their activation by glutamate results in a hyperpolarizing response. Thus, glutamate can act potentially as an inhibitory neurotransmitter, by binding to postsynaptic Group II mglurs. Given the potential importance of these receptors in synaptic processing, the development of the central nervous system, and neurological disorders, we sought to characterize the expression of mglur2 in the developing neocortex of the mouse. Therefore, we examined the distribution of mglur2 in the developing cerebral cortex. We found a general caudal to rostral gradient in the expression of these receptors, with ventral cortical regions labeled caudally and dorsal regions labeled rostrally. Limbic regions highly expressed mglur2 throughout the brain, as did sensory and motor cortical areas. Finally, other non-cortical structures, such as the thalamic reticular nucleus, amygdala, and mammillary bodies were found to have significant expression of the receptor. These results suggest that mglur2 may play important roles in mediating glutamatergic inhibition in these structures and also could have a role in shaping the development of mature neural networks in the forebrain.

关键词： Metabotropic Glutamate Receptor Mouse Cortex mglur2 Group II mglur

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The effects of NMDAR and mglur on Ap-mediated synaptic plasticity disruption in vitro

The effects of NMDAR and mGluR on Ap-mediated synaptic plast...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Ru-Yi LIN,Tian-Xiang DENG,Gui-Lan LIU,Shu-Jun XU,Xaio-Wei CHEN,Xiao-Fei WEI,Qin-Wen WANG Medical School,Ningbo University,Ningbo 315211,China

＜正＞Apart from anticholinesterases,memantine,a low-affinity NMDA receptor（NMDAR） antagonist,is the only currently approved treatment for clinical dementia of the Alzheimer *** we examined if subtype-preferring NMDA receptor antagonists could preferentially protect against the inhibition of NMDA receptor-dependent plasticity of excitatory synaptic transmission by Aβin the hippocampus by electrophysiology methods in *** selective for NMDA receptors containing NR2B but not NR2A subunits prevented Aβ-mediated inhibition of plasticity and showed *** AB,pretreatment with a high dose of NR2B antagonist ifenprodil（1μM） and Ro 25-6981（200 nM） completely inhibited *** experiments indicated that a lower dose of ifenprodil（400 nM） could partially block LTP（131±7%） and reverse Aβinhibition on LTP（139±6%）.However,Ro 25-6981（50 nM） didn’t block LTP（143±10%） but did prevent Aβinhibition on LTP（132±8%）.The selective antagonist NVP-AAM077 for NMDA receptors containing NR2A did not affect LTP on its own,and failed to prevent the inhibition of LTP by Aβ.Furthermore,we also investigated LTD which was induced by strong LFS but not weak LFS,however,weak LFS plus Aβpresented a steady LTD in both the dentate gyrus and the CA1 region of the hippocampus.D-AP5（a specific NMDAR antagonist） could not block the LTD induced by Aβwith weak LFS in the CA1 *** contrary to the D-AP5,weak LFS with Aβ-induced LTD was completely abrogated by LY341495（the group I metabotropic glutamate receptor antagonist）.Moreover,the enhancement of LTD by Ap was reversed by SB203580（p38 Mitogen-Activated Protein Kinase inhibitor） and phenylarsine oxide（membrane-permeable protein-tyrosine phosphatase inhibitor）.The present data suggest that preferentially targeting NR2B subunit-containing NMDARs with a selective antagonist may provide an effective means of preventing cognitive deficits in Alzheimer’s disease and LTD induced by Aβwith weak LFS was not NMDAR-dependent,but mG

关键词： Aβ AD synapse plasticity NMDA mglur

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麻醉药物对束缚应激大鼠脑组织EAAT和mglur表达的影响

麻醉药物对束缚应激大鼠脑组织EAAT和mGluR表达的影响

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作者：陈卓吉林大学

学位级别：硕士

异丙酚、咪唑安定及氯胺酮等麻醉药物通过调控神经和精神功能,减轻各种病因引起的损伤。本研究对复制的应激动物模型给予异丙酚及咪唑安定和氯胺酮,观察应激后大鼠胃粘膜表面的变化,研究该三种药物对大鼠脑EAAT2,3mRNA和mglur4,6mRNA及A... 详细信息

异丙酚、咪唑安定及氯胺酮等麻醉药物通过调控神经和精神功能,减轻各种病因引起的损伤。本研究对复制的应激动物模型给予异丙酚及咪唑安定和氯胺酮,观察应激后大鼠胃粘膜表面的变化,研究该三种药物对大鼠脑EAAT2,3mRNA和mglur4,6mRNA及AKTmRNA表达的影响。在复制的动物模型中发现,应激后大鼠胃粘膜表面有点条状出血或糜烂,而给予异丙酚和咪唑安定及氯胺酮后,应激所引起的胃粘膜变化明显减轻,提示这三种麻醉药物在应激过程中对机体均有保护作用。从应激大鼠脑提取RNA观察EAAT/mglur/AKT等基因mRNA的变化,结果显示与对照组相比应激组大鼠脑皮质和间脑EAAT2,3mRNA的表达明显增加;应激组大鼠给予异丙酚后脑皮质和间脑的EAAT2,3mRNA表达降低,以50mg异丙酚应激组尤为明显,与应激盐水组比较差异显著。在非应激组中,给予异丙酚后大鼠脑皮质和间脑EAAT2,3mRNA的表达也降低,两组均提示异丙酚有降低皮质和间脑EAAT2,3mRNA表达的作用。异丙酚组皮质和间脑EAAT2,3mRNA的表达趋势不同与咪唑安定组,而与氯胺酮组相同;而给予三种药物的应激组大鼠间脑mglur4,6mRNA表达趋势相同。大鼠间脑中可以看出,虽然咪唑安定应激组与应激组相比,AKTmRNA的表达略有增加,但其他各组与对照组相比AKTmRNA的表达未见明显差别。提示咪唑安定应激组AKTmRNA的表达增加可能与其药理作用有关。综合上述因素结论如下:在应激过程中异丙酚和氯胺酮及咪唑安定对机体均有保护作用;异丙酚与氯胺酮可能通过某个相同的途径对脑细胞起到保护作用。另外从异丙酚组和咪唑安定组及氯胺酮组mglurmRNA的表达变化具有相同趋势的结果,推测异丙酚的脑护机制尚不能排除与其麻醉镇静效果有关。

关键词：异丙酚应激 EAAT mglur

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Short,novel visual experience unmasks a transient,m Glu R5-dependent LTP in mouse visual cortex

Short,novel visual experience unmasks a transient,m Glu R5-d...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：蒋斌 Xiaoxiu Tie Shuo Li 中山大学中山医学院生理学系

The functional maturation of visual cortex is sculpted by visual *** examine whether novel visual experience can trigger a new LTP（experience-induced synaptic strenghthening）in visual cortex,we induced LTP in layer 2/3 pyramidal cell by stimulation of layer 4 with a pairing protocol in visual cortex of mice which were treated in a different rearing *** can be induced in the pyramidal neurons in layer 2/3 of visual cortex by stimulating layer 4 around the age of P18-20 which is completely dependent on the activation of *** the dark rearing condition（DR）,LTP was enhanced which was also mediated by NMDARs,not m Glu R5 compared with the age-matched mice in normal rearing condition（NR）.Unexpectedly,LTP switched to LTD after 10-12 hour of light exposure for DR ***,by the same protocol,robust LTP was again induced at the presence of NMDA receptor inhibitor,*** at the presence of MPEP,an m Glu R5 antagonist,LTP was completely blocked,suggesting that the visual experience per se induces synaptic further strenghthening but instead this form of plasticity required the activation of metabotropic glutamate receptors（m Glu R5）.To examine the casual link between the loss of LTP and the upsurge of synaptic drive from layer 4 to layer 2/3 during the period of light exposure,the synaptic drive was evaluated by measuring the amplitude of stimulus-evoked miniature EPSC（m EPSCs）.The synaptic drive enhanced with the time of light exposure until it became the maximal when DR micewere exposed to light for 10-12 hour indicating that the switch of LTP to LTD corresponded to the increase of synaptic drive during light ***,LTP was blocked in the mice which were injected in vivo with CPP,an NMDARs antagonist just before light *** interestingly,m Glu R5-dependent LTP was induced only at the light exposure for 10-12 hour from DR mice,while ensuing light exposure restored NMDARs-dependent *** results suggested that short,novel v

关键词： LTP Visual cortex NMDA receptor mglur Visual dperivation

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缺血性二次脑损伤大鼠脑皮层第Ⅲ组mglurs改变及意义

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第四军医大学学报 2002年第23期23卷 2117-2120页

作者：费舟章翔白红民李志刚公方和刘先珍梁景文第四军医大学西京医院全军神经外科研究所陕西西安710033

目的　研究弥漫性脑损伤 (DBI)及其合并缺血性二次脑损伤 (SBI)后大鼠脑皮层第Ⅲ组代谢型谷氨酸受体(mglurs)各亚型变化及意义 .方法　SD大鼠 175只 ,随机分为正常对照、假手术、单纯脑缺血、单纯DBI及DBI合并SBI组 .在MarmarouDBI模型... 详细信息

目的　研究弥漫性脑损伤 (DBI)及其合并缺血性二次脑损伤 (SBI)后大鼠脑皮层第Ⅲ组代谢型谷氨酸受体(mglurs)各亚型变化及意义 .方法　SD大鼠 175只 ,随机分为正常对照、假手术、单纯脑缺血、单纯DBI及DBI合并SBI组 .在MarmarouDBI模型基础上 ,制成缺血性SBI模型 ,伤后1,6 ,12 ,2 4 ,72和 16 8h进行皮层mglur4 ,6～ 8mRNA原位杂交 .结果　脑损伤后mglur6表达无明显变化 (P >0 0 5 ) ;与假手术组相比 ,单纯DBI及合并缺血性SBI组mglur4 ,mglur7和mglur8mRNA转录在损伤 1h后即有明显增加 (P mglur4 ,mglur7和mglur8参与脑损伤及缺血性SBI脑损害过程 ,可利用第Ⅲ组mglurs特异性激动剂治疗DBI及其合并SBI.

关键词：脑损伤二次脑损伤 mglur 病理生理缺血性脑损伤弥漫性脑损伤

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大鼠DBI及其合并SBI后第Ⅲ组mglurs激动剂L-AP4神经保护作用

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第四军医大学学报 2002年第23期23卷 2125-2128页

作者：白红民费舟章翔李志刚公方和刘先珍梁景文第四军医大学西京医院全军神经外科研究所陕西西安710033

目的　探讨Ⅲ组mglurs激动剂L AP4对弥漫性脑损伤 (diffusebraininjury ,DBI)及其合并二次脑损伤 (secondarybraininsult,SBI)后损伤脑组织的神经保护作用 .方法　在单纯DBI及合并SBI后 ,脑室注射L AP(10 0 μmol·L- 1 ,10 μL)或生理... 详细信息

目的　探讨Ⅲ组mglurs激动剂L AP4对弥漫性脑损伤 (diffusebraininjury ,DBI)及其合并二次脑损伤 (secondarybraininsult,SBI)后损伤脑组织的神经保护作用 .方法　在单纯DBI及合并SBI后 ,脑室注射L AP(10 0 μmol·L- 1 ,10 μL)或生理盐水 (10 μL) ,观察大鼠行为、脑组织含水量及皮层损伤神经元数变化 .结果　L AP4对DBI后大鼠死亡率、皮层损伤神经元数量及脑组织含水量无明显影响 (P >0 0 5 ) ;但可降低合并SBI组大鼠死亡率、减轻合并SBI后的脑水肿程度 ,减少神经元损伤数量 (P <0 0 5 ) .结论　L AP4对DBI合并SBI后损伤脑组织有一定的保护作用 .

关键词：脑损伤 mglur L-AP4 神经保护作用

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代谢型谷氨酸受体参与对MAPK的调节(英文)

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神经科学通报 2005年第4期21卷 308-314页

作者：毛利民杨鲁 Anish Arora Nikhil K.Parelkar 张国弛刘贤宇 Eun Sang Choe 陈海王强 Departments of Basic Medical Science University of Missouri-Kansas City School of MedicineKansasCityMOUSA. Department of Pharmacology University of Missouri-Kansas City School of PharmacyKansas CityMOUSA. Division of Biological Sciences Pusan National University PusanKorea Departments of Anesthesiology University of Missouri-Kansas City School of MedicineKansasCityMOUSA. Departments of Basic Medical Science and Anesthesiology University of Missouri-Kansas City School of MedicineKansas CityMOUSA.Department of PharmacologyUniversity of Missouri-Kansas CitySchool of PharmacyKansas CityMOUSA.

Mitogen-activated protein kinase(MAPK)在成体脑细胞高度表达并参与了多种细胞功能活动的调节。近年来,本实验室的实验结果表明五型代谢型谷氨酸受体(mglur5)可以激活纹状体培养神经元内MAPK的主要亚型ERK,ERK的激活经由两条独立的胞... 详细信息

Mitogen-activated protein kinase(MAPK)在成体脑细胞高度表达并参与了多种细胞功能活动的调节。近年来,本实验室的实验结果表明五型代谢型谷氨酸受体(mglur5)可以激活纹状体培养神经元内MAPK的主要亚型ERK,ERK的激活经由两条独立的胞内信号通路介导,传统的IP3/Ca2+通路介导了一部分的ERK激活,而mglur5的C-端结合蛋白Homer则以Ca2+-非依赖方式介导了主要的ERK激活。经两条通路激活的ERK可以协同刺激转录因子Elk-1和CREB,从而促进Elk-1和CREB敏感基因的表达。MAPK的分子生物学研究可以帮助我们了解谷氨酸受体信号转导、诱发性基因转录与表达以及神经元或突触的可塑性变化的分子机制。

关键词： ERK PP2A 磷酸酶 mglur CREB Fos 钙纹状体

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Abnormal expressions of glutamate transporters and metabotropic receptor 1 in the spontaneously epileptic rat hippocampus

Abnormal expressions of glutamate transporters and metabotro...

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中国药理学会第十次全国学术会议

作者： Ji-Qun Cai,Feng Guo,Feng Sun,Jun-Ling Yu,Qing-Hua Wang, Da-Yu Tu,Xiao-Yuan Mao,Kun-Can Wu,Rui Liu,Ni Xie (Dept of Pharmaceutical Toxicology,School of Pharmaceutical Sciences,China Medical University,92 Beier Road,Shenyang 110001 Dept of Pharmaceutical Toxicology,School of Pharmaceutical Sciences,China Medical University,92 Beier Road,Shenyang 110001)

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system,which is released into the synaptic cleft and binds to glutamate receptors resulting in the propagation of an action potential under physiological *** modulation of the synaptic activity occurs both by the removal of glutamate from the synaptic cleft and by glutamate transporters and by modulation of glutamate receptors.

关键词： Spontaneously epileptic rat Epilepsy EAATs mglur

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Phosphorylation of group I metabotropic glutamate receptors in drug addiction and translational research

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Journal of Translational Neuroscience 2016年第1期1卷 17-23页

作者： Limin Mao John Q Wang Department of Basic Medical Science School of Medicine University of Missouri-Kansas City Kansas City M0 64108 USA

Protein phosphorylation is an important posttranslational modification of group I metabotropic glutamate receptors （ mglur1 and mglur5 subtypes, mglur1/5 ） which are widely distributed throughout the mammalian brain. Several common protein kinases are involved in this type of modification, including protein kinase A, protein kinase C, and extracellular signal-regulated kinase. Through constitutive and activity-dependent phosphorylation of mglur1/5 at specific residues, protein kinases regulate trafficking, subcellular/subsynaptic distribution, and function of modified receptors. Increasing evidence demonstrates that mglur1/5 phosphorylation in the mesolimbic reward circuitry is sensitive to chronic psychostimulant exposure and undergoes adaptive changes in its abundance and activity. These changes contribute to long-term excitatory synaptic plasticity related to the addictive property of drugs of abuse. The rapid progress in uncovering the neurochemical basis of addiction has fostered bench-to-bed translational research by targeting mglur1/5 for developing effective pharmacotherapies for treating addiction in humans. This review summarizes recent data from the studies analyzing mglur1/5 phosphorylation. Phosphorylation-dependent mechanisms in stimulant-in-duced mglur1/5 and behavioral plasticity are also discussed in association with increasing interest in mglur1/5 in translational medicine.

关键词： mglur PKA PKC MAPK ERK striatum nucleus accumbens G protein-coupled receptors

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脆性X综合征代谢性谷氨酸受体信号通路与认知障碍关系进展

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广东医学 2014年第2期35卷 300-302页

作者：张瑾陈盛强广州医科大学附属第二医院神经内科广州510260

脆性X综合征（fragile X syndrome,FXS）是一种常见的遗传性智力低下疾病,认知障碍是其主要临床表现之一.目前认为,代谢性谷氨酸受体（metabotropic glutamate receptor,mglur）信号通路的异常激活是FXS各种临床症状的主要原因.探讨并总... 详细信息

脆性X综合征（fragile X syndrome,FXS）是一种常见的遗传性智力低下疾病,认知障碍是其主要临床表现之一.目前认为,代谢性谷氨酸受体（metabotropic glutamate receptor,mglur）信号通路的异常激活是FXS各种临床症状的主要原因.探讨并总结mglur及下游信号通路改变与学习记忆障碍的关系可为FXS的治疗提供更有效的靶点,本文拟综述如下.

关键词：代谢性谷氨酸受体受体信号通路脆性X综合征认知障碍 receptor 学习记忆障碍 mglur 智力低下

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