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Subcellular RNA compartmentalization

PROGRESS IN NEUROBIOLOGY 1999年第5期57卷 507-525页

作者： Mohr, E Univ Hamburg Inst Zellbiochem & Klin Neurobiol D-20246 Hamburg Germany

The phenomenon of mRNA sorting to defined subcellular domains is observed in diverse organisms such as yeast and man. It is now becoming increasingly clear that specific transport of mRNAs to extrasomal locations in nerve cells of the central and peripheral nervous system may play an important role in nerve cell development and synaptic plasticity. Although the majority of mRNAs that are expressed in a given neuron are confined to the cell somata, some transcript species are specifically delivered to dendrites and/or, albeit less frequently, to the axonal domain. The physiological role and th molecular mechanisms of mRNA compartmentalization is now being investigated extensively. Even though most of the fundamental aspects await to be fully characterized;a few interesting data are emerging. In particular, there are a number of different subcellular distribution patterns of different RNA species in a given neuronal cell type and RNA compartmentalization may differ depending on the electrical activity of nerve cells. Furthermore, RNA transport is different in neurons of different developmental stages. Considerable evidence is now accumulating that mRNA sorting, at least to dendrites and the initial axonal segment, enables local synthesis of key proteins that are detrimental for synaptic function, nerve cell development and the establishment and maintenance of nerve cell polarity. The molecular determinants specifying mRNA compartmentalization to defined microdomains of nerve cells are just beginning to be unravelled. Targeting appears to be determined by sequence elements residing in the mRNA molecule to which proteins bind in a manner to direct these transcripts along cytoskeletal components to their site of function where they may be anchored to await transcriptional activation upon demand. (C) 1999 Elsevier Science Ltd. All rights reserved.

关键词：轴突/代谢中枢神经系统/代谢树突/代谢无脊椎动物周围神经/代谢 RNA/遗传学 RNA/代谢 RNA 信使/遗传学 RNA 信使/代谢亚细胞部分/代谢转录遗传脊椎动物动物人类

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Continuous inhibition of excessive polyol pathway flux in peripheral nerves by aldose reductase inhibitor fidarestat leads to improvement of diabetic neuropathy

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JOURNAL OF DIABETES AND ITS COMPLICATIONS 1999年第3期13卷 141-150页

作者： Mizuno, K Kato, N Makino, M Suzuki, T Shindo, M Kenkyusho Co Res Dept Pharmaceut Lab Sanwa Kagaku Inabe Mie 5110406 Japan

We investigated the effects of three aldose reductase (AR) inhibitors, fidarestat, epalrestat and zenarestat, on the slowing of sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), and minimal F-wave latency prolongation in streptozotocin (STZ)-induced diabetic rats. Two weeks after STZ injection, SNCV and MNCV in the diabetic rats were significantly slower than in normal rats. Fidarestat (0.25-2 mg/kg/day), epalrestat (48 to 96 mg/kg/day) or zenarestat (10-40 mg/kg/day) was administered orally for the following 2 weeks, and SNCV, MNCV and F-wave latency were measured 3 h after final administration. Significant prolongation of minimal F-wave latency, as well as slowing of SNCV and MNCV, was found in the untreated diabetic rats 4 weeks after STZ injection. At a dose of 0.5 mg/kg/day or more fidarestat showed significant effects on these nervous dysfunctions, effects that were more potent than those shown by the other inhibitors. Furthermore, following the 2-week administration of fidarestat (1 mg/kg/day), epalrestat (48 mg/kg/day) or zenarestat (20 mg/kg/day), which began 2 weeks after STZ injection, sorbitol content in the sciatic nerve, produced by AR, a rate-limiting enzyme in the polyol pathway, was determined at 3, 8, 12, and 24 h after final administration. At each point in time, sorbitol content in the untreated diabetic rats was much higher than that in the normal control rats. Fidarestat suppressed sorbitol accumulation remarkably and continuously until 24 h after administration. On the other hand, the inhibitory effect by zenarestat declined in a time-dependent manner, and epalrestat did not decrease sorbitol content. Therefore, these results suggest that continuous inhibition of increased polyol pathway flux can improve diabetic neuropathy more potently. (C) 1999 Elsevier Science Inc.

关键词：醛还原酶/拮抗剂和抑制剂糖尿病实验性/药物疗法糖尿病实验性/代谢糖尿病神经病变/药物疗法糖尿病神经病变/代谢酶抑制剂/药理学咪唑类/治疗应用咪唑啉啶类神经传导周围神经/代谢聚合物/代谢喹唑啉类/治疗应用大鼠 Sprague-Dawley 绕丹宁/类似物和衍生物绕丹宁/治疗应用坐骨神经/代谢山梨醇/代谢噻唑烷类动物男(雄)性大鼠

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Aging in peripheral nerves: regulation of myelin protein genes by steroid hormones

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PROGRESS IN NEUROBIOLOGY 2000年第3期60卷 291-308页

作者： Melcangi, RC Magnaghi, V Martini, L Univ Milan Dept Endocrinol I-20133 Milan Italy

The process of aging deeply influences morphological and functional parameters of the peripheral nerves. Interestingly, recent observations performed in our laboratory on the rat sciatic nerves have indicated that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the messenger levels of the major peripheral myelin proteins (glycoyrotein Po, myelin basic protein and peripheral myelin protein 22). At least in the case of the Po, the low levels of its messengers and of the protein itself found in aged animals are increased by the treatment with a physiological progesterone derivative like dihydroprogesterone. It has also been found that in normal adult male rats the levels of the messengers for Po in the sciatic nel ve are increased by progesterone, dihydroprogesterone and tetrahydroprogesterone: surprisingly, the gene expression of peripheral myelin protein 22 is stimulated only by tetrahydroprogesterone. These observations have been confirmed in parallel studies performed on Schwann cell cultures. Since tetrahydroprogesterone does not bind to the progesterone receptor but is a ligand for the GABA(A) receptor, the hypothesis has been put forward that part of the steroidal effects reported might occur not through the classical progesterone receptor, but rather via an interaction with the GABA(A) receptor, In other experiments it has been found that the gene expression of Po may be decreased by orchidectomy and restored by treatment with the androgen dihydrotestosterone, Altogether, these observations suggest the future use of physiological and! or synthetic steroid hormones as a possible therapeutic approach for some pathological situations occurring in peripheral nerves during aging and demyelinating diseases. (C) 1999 Elsevier Science Ltd. All rights reserved.

关键词：衰老/生理学性腺甾类激素/代谢性腺甾类激素/药理学性腺甾类激素/治疗应用髓磷脂蛋白质类/药物作用髓磷脂蛋白质类/遗传学髓磷脂蛋白质类/代谢周围神经/药物作用周围神经/代谢周围神经/病理生理学甾类/代谢甾类/药理学甾类/治疗应用动物人类

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EFFECT OF CONDITIONING POTENTIAL ON POTASSIUM CURRENT KINETICS IN FROG NODE

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BIOPHYSICAL JOURNAL 1976年第3期16卷 261-273页

作者： PALTI, Y GANOT, G STAMPFLI, R SAAR UNIV PHYSIOL INST 1ST 665 HOMBURG FED REP GER TECHNION MED SCH DEPT PHYSIOL & BIOPHYS HAIFA ISRAEL

The kinetics of K+ conductance changes were determined in the voltage clamped frog node (Rana esculenta), as a function of conditioning prepotential. The conditioning potential duration varied from 1-50 ms and the amplitude between -60 and +130 mV (relative to rest). The conductance kinetics were determined at a single test potential of +20 mV (depolarization) by means of the slope of log [***. - nt] vs. time relationship which defines the time constant of the process (.tau.). The values of .tau., after conditioning hyperpolarizations, were around 5 ms, up to 10 times greater than values obtained following a strong depolarization. The .tau. vs. prepotential curve was sigmoid in shape. These differences were only slightly dependent on [K+]o [extracellular K+ concentration] or conditioning pulse duration. The steady-state current values were a function of conditioning potential. After conditioning hyperpolarizations, the log [***. - nt] vs. time curve could not be fitted by a single exponent regardless of the power of n chosen. The prepotential dependency of K+ current kinetics is inconsistent with the Hodgkin-Huxley axon model where the conductance parameters are assumed to be in either 1 of 2 possible states, and where the rate of transfer from 1 state to the other follows 1st order kinetics. The described kinetics may be consistent with complex multistate K+ channel models or membranes consisting of a number of types of channels.

关键词：生物转运导电性动力学膜电位模型生物学周围神经/代谢周围神经/生理学钾/代谢蛙食用动物

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PHARMACOLOGY OF OXYTOCIN AND VASOPRESSIN RECEPTORS IN THE CENTRAL AND PERIPHERAL NERVOUS-SYSTEM

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES 1992年第1期652卷 39-45页

作者： BARBERIS, C AUDIGIER, S DURROUX, T ELANDS, J SCHMIDT, A JARD, S Centre CNRS-INSERM de Pharmacologie-Endocrinologie 34094 Montpellier Cedex 5 France

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Distribution and characterization of GFP⁺ donor hematogenous cells in twitcher mice after bone marrow transplantation

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AMERICAN JOURNAL OF PATHOLOGY 2000年第6期156卷 1849-1854页

作者： Wu, YP McMahon, E Kraine, MR Tisch, R Meyers, A Frelinger, J Matsushima, GK Suzuki, K Univ N Carolina Dept Pathol & Lab Med Chapel Hill NC 27599 USA Univ N Carolina Dept Microbiol & Immunol Chapel Hill NC 27599 USA Univ N Carolina Dept Surg Chapel Hill NC 27599 USA Univ N Carolina Ctr Neurosci Chapel Hill NC 27599 USA Univ N Carolina Program Mol Biol & Biotechnol Chapel Hill NC 27599 USA

The twitcher mouse is a murine model of globoid cell leukodystropy, a genetic demyelinating disease caused by a mutation of the galactosylceramidase gene. Demyelination of the central nervous system commences around 20 postnatal days. Using GFP-transgenic mice as donors, the distribution of hematogenous cells after bone marrow transplantation was investigated in the twitcher mice. Bone marrow transplantation was carried out at 8 postnatal days. In twitcher chimeric mice examined before 30 postnatal days, numerous GFP(+) cells were detected in spleen and peripheral nerve but only a few were detected in the liver, lung, and spinal white matter. In contrast, at 35 to 40 postnatal days when demyelination is evident, many GFP(+) cells with ameboid form were detected in the white matter of the spinal cord, brainstem, and cerebrum, Approximately half of these GFP(+) cells were co-labeled with Mac-1. In twitcher chimeric mice examined after 100 postnatal days, the majority of GFP/Mac-1 double-positive cells displayed the morphological features of ramified microglia with fine delicate processes and was distributed diffusely in both gray and white matter. These results suggest that a significant number of donor hematogenous cells are able to infiltrate into the brain parenchyma, repositioning themselves into areas previously occupied by microglia, and to ameliorate lethality.

关键词：血细胞/代谢血细胞/移植骨髓移植中枢神经系统/代谢绿色荧光蛋白质类指示剂和试剂发光蛋白质类/血液发光蛋白质类/遗传学发光蛋白质类/代谢小鼠近交C57BL 小鼠神经学突变型小鼠转基因周围神经/代谢手术后医护参考值组织分布组织供者内脏/代谢动物小鼠

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RAPIDLY TRANSPORTED PROTEINS IN SENSORY, MOTOR AND SYMPATHETIC-NERVES OF ISOLATED FROG NERVOUS-SYSTEM

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BRAIN RESEARCH 1976年第3期105卷 497-515页

作者： BARKER, JL NEALE, JH GAINER, H NICHHD BEHAV BIOL BRANCH BETHESDA MD 20014 USA

The synthesis and rapid axonal transport of [35S]methionine-labeled proteins was studied using the isolated frog spinal cord and peripheral nervous system. Polyacrylamide gel electrophoresis in sodium dodecylsulfate of synthesized and transported proteins revealed similar labeling patterns of proteins transported in the sensory, motor and sympathetic systems. The relative labeling pattern of transported proteins which accumulated at ligatures in peripheral nerves was different from those obtained from ganglia or nerves and roots when they were incubated in labeled methionine. When compared with methionine-labeled protein profiles of rapid axonal transport in other species and systems, a common set of rapidly transported proteins emerges. The approximate molecular weights of these common proteins include (in 1000 daltons): 18, 24-29, 34-36, 57, 65-68, 100 and 130. These proteins may represent fundamental macromolecules involved in the general maintenance of the function of nerve processes.

关键词：自主神经纤维节后/代谢生物转运神经节脊/代谢甲硫氨酸/代谢运动神经元/代谢神经组织蛋白质类/生物合成神经组织蛋白质类/代谢神经胶质/代谢神经元传入/代谢周围神经/代谢蛙牛感觉脊髓/代谢脊神经根/代谢交感神经系统/代谢动物

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Cloning and expression study of the mouse tetrodotoxin-resistant voltage-gated sodium channel α subunit NaT/Scn11a

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2000年第1期267卷 271-277页

作者： Ogata, K Jeong, SY Murakami, H Hashida, H Suzuki, T Masuda, N Hirai, M Isahara, K Uchiyama, Y Goto, J Kanazawa, I Univ Tokyo Grad Sch Med Dept Neurol Tokyo 1138655 Japan Nagoya City Med Sch Dept Med Zool Aichi 4678601 Japan Univ Tokyo Grad Sch Frontier Sci Dept Integrat Biosci Tokyo 1130033 Japan Osaka Univ Sch Med Dept Cell Biol & Anat Osaka 5650871 Japan

We have cloned a tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel ex subunit from a mouse cDNA library and designated it as NaT, It encodes 1765 amino acid residues and is virtually identical to that of Scn11a, which has been reported recently, except for 40 nt and 14 aa substitutions. The amino acid identity of NaT/Scn11a with rat NaN/SNS2 is 88%, NaT/Scn11a was mapped to mouse chromosome 9F3-F4 by fluorescence in situ hybridization (FISH), While rat NaN/ SNS2 has been reported to be expressed specifically in the peripheral sensory neurons, NaT/Scn11a is expressed not only in the peripheral sensory neurons but also in the spinal cord, uterus, testis, ovary, placenta, and small intestine. NaT is detectable in mouse embryos 15 days postcoitus (p.c.), around the phase of organogenesis and gonadal differentiation. These findings demonstrate a unique distribution of NaT/ Scn11a and suggest some of its roles in the above-mentioned processes. (C) 2000 academic Press.

关键词：氨基酸序列染色体图克隆分子胚胎和胎儿发育基因表达调控发育期基因文库原位杂交荧光核型分析分子序列数据神经元传入/代谢器官特异性周围神经/代谢重组蛋白质类/化学重组蛋白质类/药物作用重组蛋白质类/代谢逆转录聚合酶链反应序列比对序列同源性氨基酸钠通道/化学钠通道/遗传学钠通道/生理学河豚毒素/药理学动物女(雌)性男(雄)性小鼠妊娠大鼠

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The Effect of Local Application of Vinblastine or Colchicine on Acetylcholine Accumulation in Rat Sciatic Nerve

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Acta Physiologica Scandinavica 1976年第4期96卷 478-485页

作者： Heiwall, P.‐O. Saunders, N.R. Dahlström, A. Häggendal, J. Institute of Neurobiology University of Göteborg Dept. of Pharmacology Sweden Dept. of Physiology University College London United Kingdom

The accumulation of acetylcholine (ACh) following nerve crush was inhibited by high concentrations of colchicine (10‐1, 10‐2 M) and vinblastine (10‐2‐10‐4 M) in a dose‐dependent manner. The two mitotic inhibitor... 详细信息

The accumulation of acetylcholine (ACh) following nerve crush was inhibited by high concentrations of colchicine (10^‐1, 10^‐2 M) and vinblastine (10^‐2‐10^‐4 M) in a dose‐dependent manner. The two mitotic inhibitors were effective both when applied to axons (subepineural injections) and to perikarya (injections into the lumbar intumescence). The results indicate that mitotic inhibitors, when applied locally to cholinergic motor neurons, may block the proximo‐distal transport of ACh. The possibility is discussed that this blockade is caused by an interference with a microtubule mechanism in the axons. Evidence for an increased local synthesis of ACh near the site of injection into nerves was also obtained with the highest concentrations of either substance used. © 1976 Scandinavian Physiological Society

关键词：乙酰胆碱/代谢秋水仙碱/投药和剂量秋水仙碱/药理学抑制化学性剂量效应关系药物周围神经/代谢坐骨神经/代谢长春碱/投药和剂量长春碱/药理学动物男(雄)性大鼠

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UPTAKE OF LOCAL-ANESTHETICS - MOVEMENT OF ETHANOL INTO FROG SCIATIC-NERVE

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CANADIAN ANAESTHETISTS SOCIETY JOURNAL 1975年第2期22卷 186-199页

作者： LEVY, AA WALLACE, DN DOBKIN, AB SUNY UNIV HOSP UPSTATE MED CTR DEPT ANESTHESIOL SYRACUSE NY 13210 USA

The changes of nerve action potential with time of the excised bullfrog sciaticperoneal nerve were measured at 24 degrees C with the nerve immersed in oxygenated mineral oil containing various concentrations of ethanol. One series of measurements was made with intact nerve and a range of about 20 to 110 millimolar ethanol. Another series was made with nerves in which the epineural sheath was cut open longitudinally and using a range of about 15 to 51 millimolar ethanol. The results were analysed by means of simple diffusion theory, and below applied ethanol concentrations of about 70 millimolar the latent periods and times to total block fitted the theoretical pattern well. Disagreements between theory and measurement of previous workers is explainable by their neglecting to recognize that nerve bundles do not extend to the nerve periphery. It was found that the minimum oil concentration of ethanol capable of producing total block is 15 millimolar. Above 70 millimolar, behaviour was observed consistent with nerve damage. It was found possible, by measuring the ratio latent period: time to total block, to separate the relative contribution of the epineural sheath and epineurium as a diffusion barrier to ethanol from that of the perineurium and perilemma.

关键词：动作电位麻醉药局部/代谢扩散电极肌电描记术乙醇/投药和剂量乙醇/代谢膜/代谢周围神经/代谢腓神经/代谢牛蛙坐骨神经/代谢时间因素动物

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