检索结果-内蒙古大学图书馆

Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties

NATURE NEUROSCIENCE 2000年第4期3卷 315-322页

作者： Kohda, K Wang, Y Yuzaki, M St Jude Childrens Res Hosp Dept Dev Neurobiol Memphis TN 38105 USA

Despite its importance in the cerebellum, the functions of the orphan glutamate receptor delta 2 are unknown. We examined a mutant delta 2 receptor channel in lurcher mice that was constitutively active in the absence of ligand. Because this mutation was within a highly conserved motif (YTANLAAF), we tested its effect on several glutamate receptors. Mutant delta 2 receptors showed distinct channel properties, including double rectification of the current-voltage relationship, sensitivity to a polyamine antagonist and moderate Ca2+ permeability, whereas other constitutively active mutant glutamate channels resembled wildtype channels in these respects. Moreover, the kinetics of ligand-activated currents were strikingly altered. We conclude that the delta 2 receptor has a functional ion channel pore similar to that of glutamate receptors. The motif may have a role in the channel gating of glutamate receptors.

关键词：氨基酸序列氨基酸取代抗焦虑药/药理学抗高血压药/药理学苯二氮|艹卓|类苯噻二嗪/药理学细胞系保守序列地卓西平马来酸盐/药理学兴奋性氨基酸激动剂/药理学兴奋性氨基酸拮抗剂/药理学谷氨酸/药理学离子通道闸门/药物作用离子通道闸门/遗传学红藻氨酸/类似物和衍生物红藻氨酸/药理学肾/细胞学小鼠神经学突变型分子序列数据诱变/生理学神经肌肉去极化药/药理学膜片钳术浦肯野细胞/化学浦肯野细胞/生理学喹恶啉类/药理学受体谷氨酸/化学受体谷氨酸/遗传学受体谷氨酸/代谢转染动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation

引用

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第2期97卷 871-876页

作者： Barlow, C Ribaut-Barassin, C Zwingman, TA Pope, AJ Brown, KD Owens, JW Larson, D Harrington, EA Haeberle, AM Mariani, J Eckhaus, M Herrup, K Bailly, Y Wynshaw-Boris, A Salk Inst Biol Studies Genet Lab La Jolla CA 92037 USA NIH Natl Ctr Human Genome Res Genet Dis Res Branch Bethesda MD 20892 USA CNRS Ctr Neurochim Lab Neurobiol Cellulaire Unite Propre Rech 9009Ctr Neurochim F-67084 Strasbourg France Case Western Reserve Univ Sch Med Dept Neurosci Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Alzheimers Res Lab Cleveland OH 44106 USA Louisiana State Univ Med Ctr Dept Biochem & Mol Biol New Orleans LA 70112 USA Louisiana State Univ Med Ctr Stanley S Scott Canc Ctr New Orleans LA 70112 USA Off Res Serv Vet Resources Program Bethesda MD 20892 USA Massachusetts Gen Hosp Ctr Canc Mol Oncol Lab Charlestown MA USA Univ Paris 06 Lab Dev & Vieillissement Syst Nerveux Unite Mixte Rech 7624 CNRS F-75005 Paris France

We previously generated a mouse model with a mutation in the murine Atm gene that recapitulates many aspects of the childhood neurodegenerative disease ataxia-telangiectasia. Atm-deficient (Atm-/-) mice show neurological defects detected by motor function tests including the rota-rod, open-field tests and hindpaw footprint analysis. However, no gross histological abnormalities have been observed consistently in the cerebellum of any line of Atm-/- mice analyzed in most laboratories, Therefore, it may be that the neurologic dysfunction found in these animals is associated with predegenerative lesions. We performed a detailed analysis of the cerebellar morphology in two independently generated lines of Atm-/- mice to determine whether there was evidence of neuronal abnormality, We found a significant increase in the number of lysosomes in Atm-/- mice in the absence of any detectable signs of neuronal degeneration or other ultrastructural anomalies. In addition, we found that the ATM protein is predominantly cytoplasmic in Purkinje cells and other neurons, in contrast to the nuclear localization of ATM protein observed in cultured cells, The cytoplasmic localization of ATM in Purkinje cells is similar to that found in human cerebellum, These findings suggest that ATM may be important as a cytoplasmic protein in neurons and that its absence leads to abnormalities of cytoplasmic organelles reflected as an increase in lysosomal numbers.

关键词：细胞计数细胞周期蛋白质类小脑/化学小脑/代谢小脑/超微结构细胞质/化学 DNA结合蛋白质类神经节脊/化学神经节脊/细胞学免疫组织化学溶酶体/代谢溶酶体/超微结构小鼠近交BALBC 小鼠近交系小鼠突变型显微镜检查电子神经元/化学蛋白质丝氨酸苏氨酸激酶/分析蛋白质丝氨酸苏氨酸激酶/代谢浦肯野细胞/化学浦肯野细胞/细胞学浦肯野细胞/超微结构肿瘤抑制蛋白质类动物女(雌)性男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

GABAergic mIPSCs in rat cerebellar Purkinje cells are modulated by TrkB and mGluR1-mediated stimulation of Src

引用

JOURNAL OF PHYSIOLOGY-LONDON 2000年第3期524卷 677-684页

作者： Boxall, AR Max Planck Inst Biophys Chem Arbeitsgrp Zellulare Neurobiol AG142 D-37077 Gottingen Germany

1. Whilst protein tyrosine kinase (PTK) activity can modulate expressed GABA(A) receptors in cell culture, the physiological consequences on synaptic GABA(A) receptors are unknown. This was examined using whole-cell recording of bicuculline-sensitive mIPSCs in Purkinje cells (PCs) in cerebellar slices. 2. Postsynaptic application of a peptide activator of the non-receptor PTK Src (Src-peptide) enhanced mIPSC amplitudes by 39% in the presence of brain-derived neurotrophic factor (BDNF) only;neurotrophin-3 (NT-3) was ineffective in this regard. Thus Src and TrkB (the receptor for BDNF) can physiologically interact to modulate synaptic GABA(A) receptors. 3. In the presence of BDNF, pharmacological activation of metabotrophic glutamate receptor subtype 1 (mGluR1) by (S)-3,5-dihydrophenylglycine (3,5-DHPG) also lead to a 32% enhancement of mIPSCs. This enhancement was blocked by intracellular dialysis of PCs with PP1, a selective inhibitor of Src. 4. It is concluded that, whilst GABA, receptors are not constitutively regulated by endogenous PTK activity in PCs, co-activation of TrkB by BDNF and Src by mGluR1 is required to modulate GABAergic synapses in PCs.

关键词：荷包牡丹碱/药理学脑源性神经营养因子/药理学酶抑制剂/药理学诱发电位/药物作用诱发电位/生理学兴奋性氨基酸拮抗剂/药理学 GABA拮抗剂/药理学甘氨酸/类似物和衍生物甘氨酸/药理学神经抑制/药物作用神经抑制/生理学寡肽类/代谢器官培养技术酚类/药理学浦肯野细胞/化学浦肯野细胞/代谢受体 trkB/生理学受体 GABA-A/生理学受体亲代谢性谷氨酸盐/生理学雷琐辛类/药理学星状孢子素/药理学突触/化学突触/酶学钒酸盐类/药理学 γ氨基丁酸/生理学动物大鼠

来源：评论

学校读者我要写书评

暂无评论

Dying-back of Purkinje cell dendrites with synapse loss in aging rats

引用

JOURNAL OF NEUROCYTOLOGY 1999年第3期28卷 187-196页

作者： Chen, S Hillman, DE NYU Med Ctr Dept Otolaryngol New York NY 10016 USA NYU Med Ctr Dept Physiol Biophys New York NY 10016 USA

Qualitative and quantitative changes were found in the cerebellar circuitry of old as compared to young rats. The old group had a reduced number of synapses (at least 30%), however, there was an increase in the size of remaining synaptic components (13.5% for spine head volume, 66% for bouton volume, and 17% for the area of synaptic contact zones). Furthermore, there were pronounced morphological changes in the older group appearing as: 1) prominent lipofuscin bodies in Purkinje cell somata, 2) numerous myelinated fibers in the lower part of the molecular layer, 3) tortuous Purkinje cell dendrites in a thinned molecular layer, and 4) abundant vacuolar profiles and membrane swirls in small and intermediate-sized dendrites. Our findings suggest that Purkinje cell dendrites are dying-back reducing the target field for granule cells and that remaining synaptic sites compensate by increasing synaptic contact area as well as the size of pre- and postsynaptic structures.

关键词：衰老/病理学轴突/超微结构钙结合蛋白维生素D依赖性/分析树突/化学树突/超微结构内质网/超微结构免疫组织化学脂褐素/分析髓鞘/超微结构神经组织蛋白质类/分析神经元可塑性浦肯野细胞/化学浦肯野细胞/超微结构大鼠近交F344 突触/超微结构空泡/超微结构动物女(雌)性大鼠

来源：评论

学校读者我要写书评

暂无评论

Effects of a naturally occurring neurosteroid on GABA_A IPSCs during development in rat hippocampal or cerebellar slices

引用

JOURNAL OF PHYSIOLOGY-LONDON 1999年第2期521卷 437-449页

作者： Cooper, EJ Johnston, GAR Edwards, FA UCL Dept Physiol London WC1E 6BT England Univ Sydney Dept Pharmacol Sydney NSW 2006 Australia

1. The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABA(A) receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages (similar to 10 and similar to 20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. 2. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a similar to 4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 mu M). Similar effects were seen at high concentrations of THDOC (1-2 mu M) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. 3. The effects of THDOC (1 mu M) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABA(A) receptor, rather than acting genomically. 4. At concentrations of THDOC likely to occur physiologically (50-100 nM), the decay time of IPSCs was also enhanced (25-50%) in all cerebellar cell groups tested. In contrast, at 100 nM THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. 5. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the delta subunit of the GABA(A) receptor and possibly an increase in the alpha 4 subunit.

关键词：抗焦虑药/化学抗焦虑药/药理学脱氧皮质酮/类似物和衍生物脱氧皮质酮/化学脱氧皮质酮/药理学剂量效应关系药物电刺激诱发电位/药物作用海马/化学海马/生理学膜电位/药物作用膜电位/生理学器官培养技术膜片钳术浦肯野细胞/化学浦肯野细胞/生理学大鼠 Wistar 受体 GABA-A/生理学立体异构现象突触传递/药物作用突触传递/生理学动物男(雄)性大鼠

来源：评论

学校读者我要写书评

暂无评论

Expression of thyroid receptor isoforms in the human fetal central nervous system and the effects of intrauterine growth restriction

引用

CLINICAL ENDOCRINOLOGY 2000年第4期53卷 469-477页

作者： Kilby, MD Gittoes, N McCabe, C Verhaeg, J Franklyn, JA Univ Birmingham Dept Fetal Med Div Human Reprod & Childhealth Birmingham W Midlands England Univ Birmingham Dept Fetal Med Div Med Sci Birmingham W Midlands England

BACKGROUND Congenital hypothyroidism is known to be associated with mental retardation which, if recognized promptly, is largely prevented by thyroid hormone replacement. Intrauterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity, and is also associated with neurodevelopmental delay. Fetuses with IUGR have reduced circulating concentrations of free thyroxine (T4) and free triiodothyronine (T3), leading to the hypothesis that a reduction in the tissue effects of thyroid hormones in the central nervous system (CNS) may contribute to neurodevelopmental morbidity. Since thyroid hormone effects are mediated through binding to specific nuclear thyroid hormone receptors (TRs), we have defined the pattern of TR isoform expression in the CNS throughout normal human development and have compared TR expression in the CNS of normal fetuses with those affected by IUGR. METHODS Samples of normal human fetal brain from first and second trimesters were obtained at surgical termination of pregnancy. Appropriately grown and third trimester fetuses affected by Intrauterine growth restriction (IUGR) were also investigated after unexplained stillbirth at post mortem examination. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to examine the expression of TR isoform mRNAs in frozen cerebral cortex from 10 to 16 weeks gestation. TR protein expression in human fetal brains (both cerebral hemispheres and cerebellum) was also examined in formalin fixed sections and expression of TR alpha 1, alpha 2, beta 1 and beta 2 isoforms being defined using semiquantiative immunocytochemistry. RESULTS RT-PCR revealed the presence of mRNAs encoding TR alpha 1, beta 1 and beta 2 isoforms and the nonfunctional TR alpha 2 variant in the fetal cerebral cortex from week 10 of human pregnancy. Immunostaining of the fetal brain revealed TR alpha 1 and alpha 2 protein from week 11 of human gestation. Expression of all TR isoform proteins was largely confined to

关键词：病例对照研究中枢神经系统/化学中枢神经系统/胚胎学死胎/代谢胎儿生长迟缓/代谢孕龄免疫组织化学神经元/化学蛋白质亚型/分析浦肯野细胞/化学 RNA 信使/分析受体甲状腺激素/分析受体甲状腺激素/遗传学逆转录聚合酶链反应人类婴儿新生

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：