一般口演 (Oral Sessions)

ニューロン・グリア相互作用 Interactive signaling in neurons and glial cells
O1-7-5-1 アストロサイトにおける硫化水素のシグナル機構 Signaling mechanism of hydrogen sulfide in astrocytes ○木村由佳¹, 三上義礼², 大隅貴美子¹, 津金麻美子³, 岡淳一郎⁴, 木村英雄¹ ○Yuka Kimura¹, Yoshinori Mikami², Kimiko Osumi¹, Mamiko Tsugane³, Jun-ichiro Oka⁴, Hideo Kimura¹ 独立行政法人国立精神・神経医療研究センター、神経研究所、神経薬理研究部¹, 東京大院・医・細胞分子薬理学², 大阪大院・薬・附属実践薬学教育研究センター³, 東京理科大学・薬⁴ Dept. Mol. Pharmacol. National Inst. Neuroscience, NCNP¹, Dept. Cellular Molecular Pharmacol. Univ of Tokyo, Tokyo², Dept. Pharmaceutical Sci. Osaka Univ, Osaka³, Dept. Pharmaceutical Sci.Tokyo Univ of Sci. Chiba⁴ Hydrogen sulfide (H₂S), which is produced by enzymes in various tissues, is recognized as an important mediator in multiple-physiological functions. We have shown that H₂S works as a signaling molecule in the brain. In primary rat hippocampal astrocytes, H₂S increases intracellular Ca²⁺ concentration ([Ca²⁺]_i) that propagates to neighboring astrocytes as Ca²⁺ waves. The increase in [Ca²⁺]_i depends mainly on Ca²⁺ influx from extracellular space, and is suppressed by several types of Ca²⁺ channel inhibitors, including broad spectrum TRP (transient receptor potential) channel blockers, such as lantern, gadolinium and ruthenium red. These observations suggest that H₂S may activate Ca²⁺ channels to increase [Ca²⁺]_i in astrocytes. H₂S induced-Ca²⁺ wave in astrocytes requires neuronal excitation. In neuron-astrocyte co-culture system, application of NMDA (N-methyl-D-aspartate) increases [Ca²⁺]_i in neurons followed by [Ca²⁺]_i increase in neighboring astrocytes. The observations that the NMDA-induced Ca²⁺ waves are inhibited by tetrodotoxin, Na+ channel inhibitor, and that application of NMDA to astrocytes in the absence of neurons does not induce Ca²⁺ waves in astrocytes suggest that neuronal excitation is required for the induction of Ca²⁺ waves in astrocytes.	O1-7-5-2 mGluR5-PLC-IP₃ シグナル経路に依存する自発 Ca²⁺ リズムの多細胞同期現象 Multicellular synchrony of the mGluR5-PLC-IP₃ pathway dependent spontaneous Ca²⁺ rhythms in the striatum ○田村篤史^1,2, 山田尚宏³, 矢口雄一³, 町田好男¹, 森一生¹, 小山内実^1,2 ○Atsushi Tamura^1,2, Naohiro Yamada³, Yuichi Yaguchi³, Yoshio Machida¹, Issei Mori¹, Makoto Osanai^1,2 東北大院・医¹, 大阪大院・工³ Grad Sch Med Tohoku Univ, Sendai¹, JST, CREST, Tokyo², Osaka Univ, Grad Sch Eng, Suita³ We previously reported that the long-lasting spontaneous intracellular calcium transients (spontaneous Ca²⁺ rhythms) in striatal neurons and astrocytes of GFAP-GFP mice. This spontaneous Ca²⁺ rhythms exhibited different distributions of the amplitudes, the durations, the rise slopes and the decay slopes between neurons and astrocytes. The Ca²⁺ rhythms of both neurons and astrocytes were not blocked by TTX or CNQX and AP5 administration, but blocked by thapsigargin or 2-APB administration. Thus, the spontaneous Ca²⁺ rhythms were mainly due to the Ca²⁺ release from the Ca²⁺-store via IP₃ receptor in both neurons and astrocytes. To reveal the production pathway of IP₃, we compared the Ca²⁺ rhythms between before and during application of PLC inhibitor, U73122, and the antagonist of metabotropic glutamate receptor type 5 (mGluR5) antagonist, MPEP. U73122 tended to decrease the frequency of the Ca²⁺ rhythms. MPEP blocked the Ca²⁺ rhythms in neurons and astrocytes. Thus, mGluR5-PLC-IP₃ pathway might be concerned with the Ca²⁺ rhythms in both neurons and astrocytes. The induction mechanisms of the Ca²⁺ rhythms did not depend on the action potential. However the distribution of the amplitude, the duration and the rise slope of the Ca²⁺ rhythms in neurons (not in astrocytes) shifted toward smaller values by TTX administration. Next, we conducted correlation analysis among the Ca²⁺ rhythms in multiple cells. Multicellular synchrony of the Ca²⁺ rhythms was found. The number of synchronous cells was decreased by TTX administration. Thus, neuronal activities related to the cell-to-cell interaction of the Ca²⁺ rhythms. The Ca²⁺ rhythms we found did not induced by the action potential, but were modulated by the neuronal activities.
O1-7-5-3 アストロサイトによるATP放出の解析 Analysis of ATP release from astrocytes ○稲村直子¹, , 田中謙二¹, 古家喜四夫³, 曽我部正博⁴, 池中一裕^1,2 ○Naoko Inamura¹, Hoe Ung Lee¹, Kenji Tanaka F¹, Kishio Furuya³, Masahiro Sokabe⁴, Kazuhiro Ikenaka^1,2 自然科学研究機構生理学研究所分子神経生理研究部門¹, 総研大院生命科学生理², 名古屋大革新ナノデバイス³, 名古屋大院医細胞生物⁴ Div of Neurobiol and Bioinformatics, NIPS, Aichi, Japan¹, Dept Physiol Sci, SOKENDAI, Aichi, Japan², FIRST Res Center for Innovative Nanobiodevice, Nagoya Univ, Aichi, Japan³, Dept of Physiol, Nagoya Univ Grad School of Medicine, Aichi, Japan⁴ It has been shown that astrocytes regulate neural network more directly by releasing gliotransmitter, such as glutamate and ATP. However, spatial and temporal ATP release and the mechanisms how ATP is released remain to be elucidated. We have analyzed ATP release from cultured astrocytes using a high sensitive camera. We previously showed that ATP release event with longer duration increased after glutamate stimulation. Longer duration or high intensity of ATP release were suppressed by a maxi-anion channel inhibitor, a hemichannel blocker, a P2X7 receptor inhibitor or blockers of vesicular release before stimulation. However the number of ATP release was not suppressed by these reagents. In present study we further characterized the mechanisms of ATP release. Treatment of astrocytes with all of these reagents suppressed the number of release event. These results suggest that ATP was released from astrocytes by several distinct machineries.	O1-7-5-4 Causal role of astrocyte-induced cortical synapse remodelling in neuropathic mechanical hypersensitivity in mice ○Sun Kwang Kim^1,2,3, Tatsuya Ishikawa^2,3,5, Schuichi Koizumi^3,4, Junichi Nabekura^2,3,5 Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Korea¹, Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki, Japan², Department of Pharmacology, Faculty of Medicine, Yamanashi University, Yamanashi, Japan³, Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama, Japan⁴ Peripheral nerve injury triggers maladaptive plastic changes along the somatosensory system including the primary somatosensory cortex (S1) that often leads to mechanical hypersensitivity (allodynia). We recently showed that structural synapse remodelling, e.g. increases in motility and formation of dendritic spines, in the mouse S1 is closely associated with the allodynic behaviour. It has been demonstrated that astrocytes exhibit an intracellular Ca2⁺ increase during pathological process or in response to neuronal activity and can release specific molecules to change the synaptic connections. However, whether S1 astrocytes induce synapse remodelling after nerve injury and its causal role in neuropathic hypersensitivity remains unsolved. Here, we found that Ca2⁺ signalling of S1 astrocytes markedly increased in a week following injury and subsequently, but partially, decreased. Pharmacological and genetic inhibition of S1 astrocytic Ca2⁺ significantly attenuates mechanical allodynia. Photolysis of Ca2⁺ in S1 astrocytes induced structural changes only in adjacent dendritic spines, whereas pharmacological inhibition of S1 astrocytic Ca2+ reversed the synapse remodelling following peripheral nerve injury. These results suggest that astrocytic Ca2⁺ signalling is necessary to induce the synapse remodelling in the S1 following peripheral nerve injury, which plays an important role in the development of neuropathic mechanical hypersensitivity.

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