Symposium

Symposium 27 JSN/ISN Joint Symposium Neurochemistry of Neuron-Glia interaction シンポジウム27 日本神経化学会/国際神経化学会ジョイントシンポジウムニューロンーグリア相互作用から見た神経化学

SY27-1 Astrocyte-mediated network remodeling アストロサイトによるネットワークリモデリング Koizumi Schuichi（小泉修一） Dept. Neuropharmacol., Interdisciplinary Grad. Sch. Med., Univ. Yamanashi When sense environmental changes, astrocytes become “reactive astrocytes” and contribute to both beneficial and hazardous brain functions. Here, I show astrocyte-mediated both synapse formation and elimination in neuropathic pain and ischemic models. While glial activation and altered nociceptive transmission within the spinal cord is associated with the pathogenesis of mechanical allodynia, changes in cortical circuits also accompanies peripheral nerve injury and may represent additional therapeutic targets. Soon after partial sciatic nerve ligation (PSL), a new synaptic formation was dramatically increased in the primary somatosensory cortex (S1). Using in vivo two-photon imaging of S1 spines and astrocytic Ca2+, we found that PSL induced re-emergence of mGluR5 signaling in S1 reactive astrocytes, which elicited Ca2+ excitations, synaptogenic TSP-1 release and synapse formation in the S1. Such S1 astrocyte reactivation was evident only during the first week post-injury, correlating with the temporal changes in S1 extracellular glutamate levels and dendritic spine turnover. Blocking this astrocytic signaling pathways suppressed mechanical allodynia, while activating this pathway in the absence of any peripheral injury induced long-lasting allodynia. We conclude that mGluR5-mediated Ca2+ excitation in the S1 astrocytes is a trigger for S1 circuit rewiring and contribute to neuropathic mechanical allodynia. In addition to these, reactive astrocytes cause remodeling of the neuronal network of the ischemic penumbra in the striatum. In this case, astrocytes become rather phagocytic and contribute to the synapse elimination. I will also talk the beneficial roles of reactive astrocytes in relation to phagocytosis.		SY27-2 Physiological function of microglia -Synapse microglia interaction- マイクログリアのシナプスに対する生理機能とその病態 Wake Hiroaki（和氣弘明） Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, JAPAN Microglia are sole immune responded cell in the central nervous system. Their role as immune cell has been intensely studied mainly in pathological conditions. Their activation with neurodegeneration promote cytokines and neurotrophic factor release, resulting in their neuroprotective or neurotoxic role. Although they are still existing in physiological brain, their physiological function was long debated because of the technical limitation to handle the immune cells. Using recent developed of optical imaging technique, including in vivo two photon microscope, microglia are found to be highly motile cell, extending and retracting their process without their cell soma movement to contact on the synaptic elements. Here, we show the physiological function of microglia especially their interaction with synapses and discuss their role in physiological brain. And we also suggest their contribution on psychiatric disease formation.

SY27-3 Myelin proteomics: A tool to discover novel myelin proteins with relevance for a healthy nervous system Werner Hauke Max Planck Institute for Experimental Medicine, Germany Myelin can be biochemically purified and its protein composition can be systematically determined by mass spectrometry. Using a recently established workflow, label-free proteome analysis now allows the identification and simultaneous relative quantification of 500-850 distinct proteins in purified myelin. As the proteomic profile of myelin is highly reproducible, we are currently approaching its maturation, ageing and evolution, as well as changes in myelin-related pathology. I will discuss the power of the method in discovering novel myelin proteins with relevance for the normal structure and function of myelinated axons and their myelin sheaths.		SY27-4 Two modes of enteric gliotransmission differentially affect gut physiology Vladimir Parpura¹，Grubišić Vladimir^1,2 ¹Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA ²Department of Physiology, Neuroscience Program, Michigan State University, East Lansing, MI, USA Enteric glia (EG) in the enteric nervous system (ENS) can modulate neuronally regulated gut functions. Using molecular genetics, we assessed the effects that molecular entities expressed in EG and otherwise mediating two distinct mechanisms of gliotransmitter release, connexin 43 (Cx43) hemichannel vs. Ca²⁺-dependent exocytosis, have on gut function. The expression of mutated Cx43^G138R (which favors hemichannel, as opposed to gap-junctional activity) in EG increased gut motility in vivo, while a knock-down of Cx43 in EG resulted in the reduction of gut motility. As the former manipulation is based on a Cx43 point mutation seen in human pathology of oculo-dento-digital dysplasia (ODDD) , these are clinically relevant findings. Inhibition of Ca²⁺-dependent exocytosis in EG did not affect gut motility in vivo. Rather, it increased the fecal pellet fluid content. Hampering either Cx43 expression or Ca²⁺-dependent exocytosis in EG had an effect on colonic migrating motor complexes, mainly decreasing frequency and velocity of contractions ex vivo. Thus, EG can differentially modulate gut reflexes using the above two distinct mechanisms of gliotransmission.

SY27-5 Regulation of astrocyte production during neocortical development 大脳新皮質アストロサイトの分化制御 Gotoh Yukiko（後藤由季子），表　伯俊，LANJAKORNSIRIPAN DARIN，川口大地 Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of Tokyo Non-pialneocortical astrocytes have historicallybeen thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two-and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorialvolume and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated in reelerand Dab1conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite forthe observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.