上海生科院段树民研究小组发表《自然》子刊文章

上海生科院段树民研究小组发表《自然》子刊文章

　　

生物通综合：来自中科院上海生命科学研究院神经科学研究所的研究人员在原来工作的基础上，进一步研究发现星形胶质细胞的溶酶体含有丰富的ATP, 并可在一定的生理和病理刺激下呈现不同程度的分泌，这种不同模式的分泌可能在介导胶质细胞的各种神经生理和病理作用方面具有重要意义。这一研究成果于7月8日在《自然·细胞生物学》(Nature Cell Biology)在线发表。

领导这一研究的是神经科学研究所段树民教授，参予实验的还包括张志君、陈罡、周伟等。

溶酶体被认为是细胞的“消化器官”，对吞噬到细胞内的‘营养物质”和细胞“废弃物质” 的降解起关键作用。胶质细胞溶酶体具有释放ATP功能的发现，对理解和更深入研究胶质细胞在脑内的功能具有重要意义。由于ATP也是很多组织细胞普遍应用的信号分子，该研究工作提示进一步研究其它细胞的溶酶体是否也具有释放ATP及其功能具有重要意义。

附：
生物学家——段树民  
 
 段树民  中国科学院神经科学研究所研究员。博士生导师，中国科学院“****”获者。1982年安徽蚌埠医学院毕业，1991年获日本九洲大学医学博士学位。1992-1994在中国科学院上海脑研究所做博士后 研究。1995-1996，日本九洲大学世川医学奖学金特别研究员。1996-1999先后在美国夏威夷大学Bekesy神经生物实验室、加州大学旧金山分校神经科学实验室做访问学者。研究兴趣为受体、转运蛋白、离子通道及其信息转导机制。近几年主要研究星形胶质细胞参与神经元信息处理的机理。

Shumin Duan , Ph.D.

Rm 238, SIBS Building
Institute of Neuroscience
Chinese Academy of Sciences
Shanghai 200031,
China
Phone: [phone]
Email: shumin@ ion.ac.cn
 
简单介绍：
Dr. Shumin Duan is an investigator and head of Laboratory of Synapse Development and Plasticity. He graduated from Bengbu Medical College in 1982 and received his Ph. D. from Kyushu University in Japan in 1991. In 1995-1996 he was awarded a Sasakawa medical senior researcher fellowship and worked at Kyushu University, Japan. He was also a visiting scientist at University of Hawaii and University of California at San Francisco during 1997-99. His recent interests include the role of transmitter receptors and transporters in neuronal signaling functions and the role of astrocytes in synaptogenesis and synaptic plasticity.
 
研究领域：
We are interested in the mechanisms underlying synaptogenesis and activity-dependent synaptic plasticity. In particular, we are interested in exploring what roles the glial cells, especially astrocytes, may play in these processes. Although glial cells constitute a large proportion of cells in the brain - from 25% in Drosophila to 90% in human, their potential roles in neuronal functions have not attracted much attention of neuroscientists over the past century. The goal of our research program is to examine the potential roles of glial cells in synaptogenesis and synaptic plasticity, and to understand their underlying cellular and molecular mechanisms.
 
 
正在研究的课题：
Active role of astrocytes in long-term synaptic plasticity.
Although glial cells have been reported to play important roles in various neuronal functions including neurogenesis, synaptogenesis, and modulating synaptic transmission, it is not clear whether and how glial cells contribute to long-term potentiation (LTP), - a form of synaptic plasticity believed to be a cellular basis for learning and memory. To directly address this issue, we have established two types of hippocampal cultures - neurons cultured on a layer of astrocytes (mixed cultures) or in glia conditioned medium (GCM) without direct contact with astrocytes (GCM cultures). We found that LTP could be evoked in mixed cultures but not in GCM cultures. Further results from both hippocampal slices and cultured neurons indicate that, by providing extracellular D-serine that facilitates activation of NMDA receptors, astrocytes directly supports the induction of LTP. We have also directly recorded astrocyte currents in hippocampal slice in response to stimulation of Schaffer collaterals. Interestingly, induction of LTP in CA1 neurons also induced long-term increase in astrocyte currents in response to Schaffer collateral stimulation. We are currently examining the underlying mechanisms and its functional significance of the latter form of neuron-glia interaction.
Activity- dependent heterosynaptic modulation mediated by astrocyte released factors.
High levels of neuronal activity have been reported to cause spillover of neurotransmitter to neighboring synapses and induce heterosynaptic modulation via presynaptic receptors, suggesting that neuronal information processing involves not only homosynaptic transmission via activated synaptic connections but also heterosynaptic interactions between adjacent synaptic inputs. Using dual whole-cell recordings from pairs of interconnected hippocampal neurons in mixed cultures and GCM cultures, we found that glutamatergic synaptic activity activates non-NMDA receptors of nearby astrocytes and induces ATP release from these cells, which in turn causes heterosynaptic suppression. Thus, besides the spillover of neurotransmitters from synapses, signaling molecule released from astrocytes, e.g., ATP, can also mediate neuronal activity-dependent heterosynaptic modulation. Such neuron-glia crosstalks may play a role in activity-dependent signal processing and plasticity of neural networks. We are further examining if such neuron-glia crosstalk also exists in more intact tissues, using brain slice preparations.
Activity-dependent synaptogenesis.
The development of synaptic connections -the formation, elimination, stabilization and maturation of synapses - is shaped by neuronal activity, a process critical for experience-dependent refinement of neuronal circuits. Using a combination of experimental approaches, including electrophysiology, immunochemistry, GFP-linked gene transfection, two-photon fluorescence microscopy, and calcium imaging, we are studying the trafficking of pre- and postsynaptic molecules induced by neuronal activities in cultured neurons and brain slices. In particular, we are interested in determining whether astrocytes are involved in this neuronal activity-dependent synapse development. We are also interested in studying how 'new' neurons derived from neural stem cells become incorporated into (form synapses with) existing neuronal circuits.
Guidance of Glial Cell Migration.
Growth and migration of glial processes are important not only in neuronal development, e.g., guiding neuronal migration , but also in neuronal degeneration and regeneration, but the underlying mechanisms are largely unknown. We are interested in studying whether glia cell migration and process extension share the same molecules and signal transduction mechanisms with that of neuronal migration and axon guidance, and how guidance of migration and growth of these neurons and glial cells are regulated through their reciprocal interactions.
 
主要发表文章：
Wanhua Shen, Bei Wu, Zhijun Zhang,Ying Dou, Zhi-ren Rao,Yi-ren Chen,and Shumin Duan （2006）Activity-Induced Rapid Synaptic Maturation Mediated by Presynaptic Cdc42 Signaling. Neuron 50, 401–414
Woo-Ping Ge, Xiu-Juan Yang, Zhijun Zhang, Hui-Kun Wang, Wanhua Shen, Qiu-Dong Deng, Shumin Duan. (2006) Long-Term Potentiation of Neuron-Glia Synapses Mediated by Ca2+-Permeable AMPA Receptors. Science 312, 1533-1537.
Li, C., Lu, J., Wu, J., Duan, S., and Poo, M. (2004) Bidirectional Modification of Presynaptic Neuronal Excitability Accompanying Spike Timing-Dependent Synaptic Plasticity. Neuron 41, 257-268.
Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., Poo, M., and Duan, S. (2003) Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. PNAS, 100: 15194-15199.
Zhang, J., Wang, H., Ye, C., Ge, W., Chen, Y., Jiang, Z., Wu, C., Poo, M. and Duan, S. (2003) ATP Released by Astrocytes Mediates Glutamatergic Activity-Dependent Heterosynaptic Suppression. Neuron, 40: 971-982.
Duan, S., Anderson C. M. , Keung, E. C., Chen, Y., Chen, Y., and Swanson R. A.(2003) P2X7 Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes. J Neurosci, 23: 1320-1328
Wang, Z., Xu, N., Wu,CP., Duan, S., and Poo, M. (2003) Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications. Neuron, 37: 463-472
Yuan, X., Jin, M., Xu, X., Wu, CP., Poo, M., and Duan, S.(2003) Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nature Cell Biol , 5, 38 - 45 
Xiang, Y., Li, Y., Zhang, Z., Wang, S., Yuan, X.B., Wu, C., Poo, M. and Duan S., (2002) Nerve growth cones guidance mediated by G-protein-coupled receptors. Nature Neuroscience, 5, 843 - 848
Anderson, C.M., Norquist, B.A., Vesce, S., Nicholls, D.G., Soine, W.H., Duan, S., and Swanson, R.A. (2002) Barbiturates Induce Mitochondrial Depolarization and Potentiate Excitotoxic Neuronal Death. J Neurosci, 22: 9203-9209
Duan, S., Cooke, I.M., (2000)Glutamate and GABA activate different receptors and Cl(-) conductances in crab peptide-secretory neurons. J Neurophysiol 83: 31-37
Swanson, R.A., Duan, S., (1999) Regulation of glutamate transporter function. Neuroscientist, 5: 280-282
Duan, S., Cooke, I.M., (1999) Selective inhibition of transient K+ current by La3+ in crab peptide-secretory neurons. J Neurophysiol 81:1848-1855
Duan, S., Anderson, C.M., Stein, B.A., Swanson, R.A., (1999) Glutamate induces rapid upregulation of astrocyte glutamate transport and cell-surface expression of GLAST. J Neurosci 19: 10193-10200