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Stem cells in the adult mammalian central nervous system

CURRENT OPINION IN NEUROBIOLOGY 1999年第1期9卷 135-141页

作者： Temple, S Alvarez-Buylla, A Albany Med Coll Dept Pharmacol & Neurosci A60 Albany NY 12208 USA Rockefeller Univ New York NY 10021 USA

Over the past year, evidence has accrued that adult CNS stem cells are a widespread progenitor cell type. These cells may normally replace neurons and/or glia in the adult brain and spinal cord, Advances have been made in understanding the signals that regulate stem cell proliferation and differentiation. A deeper understanding of the structure of germinal zones has helped us move towards identifying stem cells in vivo. Recent studies suggest that the fate of stem cell progeny in vivo may be linked to the complexity of the animal's environment.

关键词：年龄因素细胞分化/药物作用中枢神经系统/细胞学表皮生长因子/药理学成纤维细胞生长因子2/药理学干细胞/细胞学干细胞/药物作用动物小鼠大鼠

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Visualization of the entire trajectory of long axons of single mammalian CNS neurons

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BRAIN RESEARCH BULLETIN 1999年第5-6期50卷 387-388页

作者： Shinoda, Y Tokyo Med & Dent Univ Sch Med Dept Syst Neurophysiol Bunkyou Ku Tokyo 113 Japan

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lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS

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NEURON 1999年第1期23卷 105-114页

作者： Miwa, JM Ibanez-Tallon, I Crabtree, GW Sánchez, R Sali, A Role, LW Heintz, N Rockefeller Univ Howard Hughes Med Inst Mol Biol Lab New York NY 10021 USA Rockefeller Univ Mol Biophys Lab New York NY 10021 USA Columbia Univ Dept Anat Ctr Neurobiol New York NY 10032 USA

Elapid snake venom neurotoxins exert their effects through high-affinity interactions with specific neurotransmitter receptors. A novel murine gene, lynx1, is highly expressed in the brain and contains the cysteine-rich motif characteristic of this class of neurotoxins. Primary sequence and gene structure analyses reveal an evolutionary relationship between lynx1 and the Ly-6/neurotoxin gene family, lynx1 is expressed in large projection neurons in the hippocampus, cortex, and cerebellum. In cerebellar neurons, lynx1 protein is localized to a specific subdomain including the soma and proximal dendrites. lynx1 binding to brain sections correlates with the distribution of nAChRs, and application of lynx1 to Xenopus oocytes expressing nAChRs results in an increase in acetylcholine-evoked macroscopic currents. These results identify lynx1 as a novel protein modulator for nAChRs in vitro, which could have important implications in the regulation of cholinergic function in vivo.

关键词：氨基酸序列/遗传学环蛇毒素类/遗传学中枢神经系统/细胞学中枢神经系统/代谢膜糖蛋白类/遗传学膜糖蛋白类/代谢膜糖蛋白类/生理学分子序列数据多基因族/遗传学神经元/代谢神经肽类/遗传学神经肽类/代谢神经肽类/生理学卵母细胞受体烟碱/代谢爪蟾属动物女(雌)性小鼠

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Quantal currents at single-site central synapses

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JOURNAL OF PHYSIOLOGY-LONDON 2000年第1期526卷 3-11页

作者： Auger, C Marty, A UCL Dept Physiol London WC1 E6BT England Max Planck Inst Biophys Chem Arbeitsgrp Zellulare Neurobiol D-37077 Gottingen Germany

The mode of operation of synaptic transmission has been primarily worked out at the vertebrate neuromuscular junction, thus providing a framework for the interpretation of studies at central synapses. However, differences have been found between the two systems, and a coherent model is still lacking for central synapses. Research in this area revolves around several questions. (1) Is the variability of quantal amplitudes determined pre- or postsynaptically? (2) What is the occupancy of postsynaptic receptors following the release of a synaptic vesicle? And (3) does multivesicular release occur at single release sites following one presynaptic action potential? To answer these questions, it is essential to investigate synaptic processes at the level of single release sites. This is technically difficult because of the complex morphology and small dimensions of central synapses. Nevertheless significant advances have been made in the past few years.

关键词：动作电位/药物作用苯二氮|艹卓|类/药理学结合竞争性/药物作用细胞培养的中枢神经系统/细胞学中枢神经系统/药物作用中枢神经系统/代谢诱发电位/药物作用兴奋性突触后电位/药物作用谷氨酸/代谢海马/细胞学海马/药物作用海马/代谢神经元/细胞学神经元/药物作用神经元/代谢膜片钳术受体 AMPA/代谢受体 N-甲基-D-天冬氨酸/代谢受体神经递质/拮抗剂和抑制剂受体神经递质/代谢蜘蛛毒液类/药理学突触/药物作用突触/代谢脊椎动物动物

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Asymmetric division of Drosophila neural stem cells:: a basis for neural diversity

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CURRENT OPINION IN NEUROBIOLOGY 2000年第1期10卷 38-44页

作者： Matsuzaki, F Tohoku Univ Inst Dev Aging & Canc Dept Dev Neurobiol Japan Sci & Technol CorpCRESTAoba Ku Sendai Miyagi 9808575 Japan

Recent studies of Drosophila neural precursor cells have unveiled the essential roles played by asymmetric cell divisions in the determination of cell fates during neural development. Our understanding now extends to the molecular nature of the cell polarity that underlies asymmetric divisions. This polarity is conserved among neural stem cells, epithelial cells and fertilized eggs.

关键词：细胞分化细胞分裂细胞极性中枢神经系统/细胞学中枢神经系统/胚胎学保守序列果蝇黑腹/细胞学果蝇黑腹/胚胎学上皮细胞/细胞学上皮细胞/代谢有丝分裂纺锤体/代谢神经元/细胞学神经元/代谢 RNA 信使/遗传学 RNA 信使/代谢干细胞/细胞学干细胞/代谢动物

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Recombinant adeno-associated virus type 2, 4, and 5 vectors: Transduction of variant cell types and regions in the mammalian central nervous system

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第7期97卷 3428-3432页

作者： Davidson, BL Stein, CS Heth, JA Martins, I Kotin, RM Derksen, TA Zabner, J Ghodsi, A Chiorini, JA Univ Iowa Coll Med Dept Internal Med Program Gene Therapy Iowa City IA 52242 USA Univ Iowa Coll Med Dept Neurol Iowa City IA 52242 USA Univ Iowa Coll Med Dept Neurosurg Iowa City IA 52242 USA NHLBI Mol Hematol Branch NIH Bethesda MD 20892 USA Natl Inst Dent & Craniofacial Res Gene Therapy & Therapeut Branch NIH Bethesda MD 20892 USA

Recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in the central nervous system (CNS), but it is not known how other rAAV serotypes perform as CNS gene transfer vectors. Serotypes 4 and 5 are distinct from rAAV2 and from each other in their capsid regions, suggesting that they may direct binding and entry into different cell types. In this study, we examined the tropisms and transduction efficiencies of P-galactosidase-encoding vectors made from rAAV4 and rAAV5 compared with similarly designed rAAV2-based vectors. Injection of rAAV5 beta-galactosidase (beta gal) or rAAV4 beta gal into the lateral ventricle resulted in stable transduction of ependymal cells, with approximately 10-fold more positive cells than in mice injected with rAAV2 beta gal. Major differences between the three vectors were revealed upon striatal injections. Intrastriatal injection of rAAV4 beta gal resulted again in striking ependyma-specific expression of transgene, with a notable absence of transduced cells in the parenchyma. rAAV2 beta gal and rAAV5 beta gal intrastriatal injections led to beta-gal-positive parenchymal cells, but unlike rAAV2 beta gal, rAAV5 beta gal transduced both neurons and astrocytes. The number of transgene-positive cells in rAAV5 beta gal-injected brains was 130 and 5,000 times higher than in rAAV2 beta gal-injected brains at 3 and 15 wk, respectively. Moreover, transgene-positive cells were widely dispersed throughout the injected hemisphere in rAAV5 beta gal-transduced animals. Together, our data provide in vivo support for earlier in vitro work, suggesting that rAAV4 and rAAV5 gain cell entry by means of receptors distinct from rAAV2. These differences could be exploited to improve gene therapy for CNS disorders.

关键词：中枢神经系统/细胞学中枢神经系统/病毒学依赖病毒/遗传学遗传载体免疫组织化学小鼠近交C57BL 重组遗传转导遗传 β半乳糖苷酶类/遗传学动物男(雄)性小鼠

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Colocalization of neurotransmitter receptors on astrocytes in explant cultures of rat CNS

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NEUROCHEMISTRY INTERNATIONAL 2000年第4-5期36卷 301-311页

作者： Hösli, E Hösli, L Univ Basel Dept Physiol CH-4051 Basel Switzerland

In recent years evidence has accumulated that astrocytes express functional receptors for a variety of neurotransmitters/neuromodulators. By means of electrophysiological and combined autoradiographic and immunohistochemical methods we have demonstrated the colocalization of cholinergic, adrenergic and peptidergic receptors on astrocytes in explant cultures from various regions of rat central nervous system. A great number of biochemical and electrophysiological studies from other laboratories have shown that most of the neurotransmitters exert their effects on second messenger systems and on Ca2+ - activated K+-channels. Furthermore, certain neurotransmitters are involved in the regulation of energy metabolism by stimulating enzymatic breakdown of glycogen in astrocytes. It was suggested that there is a cross-talk between the various neurotransmitter receptors on the glial membrane and that these receptors act in a synergistic or antagonistic way. The coexistence of cholinergic and peptidergic receptors on astrocytes is of great interest since both neurotransmitter systems are involved in cognitive functions and are impaired in patients with Alzheimer's dementia. The question is therefore raised whether not only neurones but also astrocytes might be involved in neurodegenerative disorders such as Alzheimer's disease. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：星形细胞/代谢星形细胞/生理学放射自显影术中枢神经系统/细胞学中枢神经系统/代谢中枢神经系统/生理学培养技术电生理学/方法免疫组织化学神经肽类/代谢受体肾上腺素能/代谢受体胆碱能/代谢受体神经递质/代谢受体肽/代谢组织分布动物大鼠

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Increased tumor necrosis factor and interleukin-6 production in the central nervous system of interleukin-10-deficient mice

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BRAIN RESEARCH 2000年第1-2期869卷 241-243页

作者： Agnello, D Villa, P Ghezzi, P Mario Negri Inst Pharmacol Res Lab Neuroimmunol I-20157 Milan Italy CNR Cellular & Mol Pharmacol Ctr I-20129 Milan Italy

Interleukin-10 (IL-10) inhibits tumor necrosis factor (TNF) production. We investigated the role of endogenous IL-IO in brain TNF production. We injected IL-10-knockout mice with lipopolysaccharide (LPS,2.5 mu g/mouse i.c.v.). Brain TNF and IL-6 levels were more elevated and persisted longer in IL-10-deficient mice compared with wild type mice, suggesting that IL-10 is an important negative feedback inhibitor of TNF and IL-6 production in the CNS. (C) 2000 Elsevier Science BN. All rights reserved.

关键词：中枢神经系统/细胞学中枢神经系统/代谢白细胞介素10/缺乏白细胞介素6/代谢小鼠近交C57BL 小鼠基因敲除肿瘤坏死因子α/代谢动物男(雄)性小鼠

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Role of astrocytes in the clearance of excess extracellular potassium

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NEUROCHEMISTRY INTERNATIONAL 2000年第4-5期36卷 291-300页

作者： Walz, W Univ Saskatchewan Dept Physiol Saskatoon SK S7N 5E5 Canada

The development of concepts describing potassium clearance mechanisms in the mammalian central nervous system in the last 35 years is reviewed. The pattern of excess potassium in the extracellular space is discussed as are the implications of these potassium levels for neuronal excitability. There is a systematic description of the available evidence for astrocytic involvement in situ. The three possible astrocytic potassium clearance mechanisms are introduced: spatial buffer mechanism;carrier-operated potassium chloride uptake as well as channel-operated potassium chloride uptake. The three mechanisms are compared and their compatibility is discussed. Evidence is now available showing that at least two of these if not all three mechanisms co-exist and complement each other. Finally, it is concluded that these potassium movements are not used as a signal system, only as a homeostatic feedback mechanisms. Such a genuine signal. system involving glial elements exists - but it is based on calcium waves. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：星形细胞/生理学中枢神经系统/细胞学中枢神经系统/代谢细胞外间隙/代谢神经元/生理学钾/代谢钾/生理学信号传导/生理学动物

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Glial cells and volume transmission in the CNS

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NEUROCHEMISTRY INTERNATIONAL 2000年第4-5期36卷 397-409页

作者： Syková, E Chvátal, A Charles Univ Dept Neurosci Fac Med 2 Prague 14220 4 Czech Republic Acad Sci Czech Republ Inst Expt Med Prague 14220 4 Czech Republic

Although synaptic transmission is an important means of communication between neurons, neurons themselves and neurons and glia also communicate by extrasynaptic "volume" transmission, which is mediated by diffusion in the extracellular space (ECS). The ECS of the central nervous system (CNS) is the microenvironment of neurons and glial cells. The composition and size of ECS change dynamically during neuronal activity as well as during pathological states. Following their release, a number of neuroactive substances, including ions, mediators, metabolites and neurotransmitters, diffuse via the ECS to targets distant from their release sites. Glial cells affect the composition and volume of the ECS and therefore also extracellular diffusion, particularly during development, aging and pathological states such as ischemia, injury, X-irradiation, gliosis, demyelination and often in grafted tissue. Recent studies also indicate that diffusion in the ECS is affected by ECS volume inhomogeneities, which are the result of a more compacted space in certain regions, e.g. in the vicinity of oligodendrocytes. Besides glial cells, the extracellular matrix also changes ECS geometry and forms diffusion barriers, which may also result in diffusion anisotropy. Glial cells therefore play an important role in extrasynaptic transmission, for example in functions such as vigilance, sleep, depression, chronic pain, LTP, LTD, memory formation and other plastic changes in the CNS. In turn, ECS diffusion parameters affect neuron-glia communication, ionic homeostasis and movement and/or accumulation of neuroactive substances in the brain. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：衰老/生理学中枢神经系统/细胞学中枢神经系统/生理学扩散细胞外间隙/生理学神经胶质/生理学突触传递/生理学动物

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