Modulation of synaptic functions by astrocytes

• Project/Area Number: 10214203
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: KUDO Yoshihisa School of Life Science, Tokyo University of Pharmacy and Life Science, Professor, 生命科学部, 教授 (20080179)
• Co-Investigator(Kenkyū-buntansha): KIYAMA Hiroshi Osaka City University Graduate School of Medicine, Medical School, Professor, 医学部, 教授 (00192021) ; MORITA Mitsuhiro School of Life Science, Tokyo University of Pharmacy and Life Science, Research Associate, 生命科学部, 助手 (50297602)
• Project Period (FY): 1998 – 2001
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥24,600,000 (Direct Cost: ¥24,600,000); Fiscal Year 2001: ¥5,400,000 (Direct Cost: ¥5,400,000); Fiscal Year 2000: ¥5,400,000 (Direct Cost: ¥5,400,000); Fiscal Year 1999: ¥6,300,000 (Direct Cost: ¥6,300,000); Fiscal Year 1998: ¥7,500,000 (Direct Cost: ¥7,500,000)
• Keywords: astrocytes / calcium oscillation / cytokines / glutamate / lipopolysaccharide / feedback mechanism / neuron / カルシウム / 成長因子 / NO / Cre-loxP / シュワン細胞 / アストログリア / トランスポーター電位 / 神経栄養因子 / エンドセリン / シナプス / グルタミン酸トランスポーター / t-ACPD / ディファレンシアルディスプレー法 / メタロペプチダーゼ / アンチオキシダント / グリア細胞 / Ca^<2+>オシレーション / 遺伝子クローニング

Research Abstract

To explore the variability in the calcium response of astrocytes to neurotransmitters, we examined factors affecting the pattern of calcium response in cultured cells and investigated the consequences of the astrocyte calcium response in slice preparations. Growth factors (epidermal growth factor plus basic fibroblast growth factor) promoted calcium oscillation in response to glutamate, ATP, or thimerosal (which directly activates the inositol-1, 4, 5 trisphosphate receptor), enlargement of the calcium store, and the development of a hypertrophic morphology, all of which were mediated by the mitogen-activated protein kinase (MAPK) cascade. All three effects were suppressed by proinflammatory cytokines (interleukin-1b or tumor necrosis factor-a), lipopolysaccharide, or a MAPK inhibitor, U0126 suggesting dual regulation of calcium oscillation in astrocytes by factors affecting brain function and pathology. In slice preparations, a metabotropic glutamate receptor agonist induced a similar calcium oscillation in neurons which was independent of synaptic transmission, indicating that the calcium response in astrocytes affects the activity of neighboring neurons as a feedback mechanism of neuronal activity.

Research Products

• [Publications] Yasuda H, Higashi H, Kudo Y, 他5名: "Imaging of calcineurin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex"Eur J Neurosci.. 17. 287-297 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsuchiya R, Yoshiki F, Kudo Y, Morita M.: "Cell type-selective expression of green fluorescent protein and the calcium indicating protein, yellow cameleon, in rat cortical primary cultures"Brain Res.. 956. 221-229 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki Y, (Kudo, Y.)ら13名: "Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex"Neuron. 35. 907-920 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Enoki R, Namiki M, Kudo Y, Miyakawa H: "Optical monitoring of synaptic summation along the dendrites of CA1 pyramidal neurons"Neuroscience. 113. 1003-1014 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishii, W., Shoda, T., Kudo, Y., Takahashi, K.: "Insitu visualization of caspase-1-like activty associated with promotion of hippocampal cell death"FEBS letters. 518. 149-153 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 工藤佳久, 吉田佳督, 森田光洋: "脳機能の解明(アストロサイトとニューロンのクロストークとその生理学的意義)"赤池紀夫、東 英穂、阿部康二、久保千春(ガイア出版会). 570 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 工藤佳久: "神経研究の進歩 特集 ダリアの生物科学"医学書院. 120 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yasuda H, Higashi H, Kudo Y, Inoue T, Hata Y, Mikoshiba K, Tsumoto T.: "Imaging of calcineurin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex"Eur J Neurosci.. 17(2). 287-297 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuchiya R, Yoshiki F, Kudo Y, Morita M.: "Cell type-selective expression of green fluorescent protein and the calcium indicating protein, yellow cameleon, in rat cortical primary cultures"Brain Res.. 956(2). 221-229 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sasaki Y, Cheng C, Uchida Y, Nakajima O, Ohshima T, Yagi T, Taniguchi M, Nakayama T, Kishida R, Kudo Y, Ohno S, Nakamura F, Goshima Y.: "Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex"Neuron. 35(5). 907-920 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Enoki R, Namiki M, Kudo Y, Miyakawa H.: "Optical monitoring of synaptic summation along the dendrites of CA1 pyramidal neurons"Neuroscience. 113(4). 1003-1014 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishii, W., Shoda, T., Matsumoto, N., Nakamura, T., Kudo, Y., and Takahashi, K.: "Insitu visularization of caspse-1-like acitivty associated with promotion of hippocampal cell death"FEBS letters. 518. 149-153 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Inoue, M., Hashimoto, Y., Kudo, Y., Miyakawa: "Dendritic attenuation of synaptic potentials in the CA1 region of rat hippocampal slices detected with a optical method"Europ. J. Neurosceince. 13(1). 1-12 (2001)
• [Publications] Enoki, R., Inoue, M., Hashimoto, Y., Kudo, Y., Miyakawa, H: "GABAergic control of synaptic summation in hippocampal CA1 pyramidal neurons"Hippocampus. 11(6). 683-689 (2001)
• [Publications] Uchino, S.Nakamura, T.Makamura, K., N-Iijima, S., Mishina, M.ohsaka, S., Kudo, Y.: "A real time, two dimensional visualization of ischemia-induced glutamate release from hippocampal slices"Europ. J. Neurosci.. 13(2). 670-678 (2001)
• [Publications] Iida N, Namikawa K, Kiyama H, Ueno H, Nakamura S, Hattori S: "Requirement of Ras for the activation of mitogen-activated protein (MAP) kinase by calcium influx, cAMP and neurotrophin in hippocampal neurons"J.Neurosci. 21(17). 6459-6466 (2001)
• [Publications] Shirotani K, Tsubuki S, Iwata N, Takaki Y, Harigaya W, Maruyama K, Kiryu-SeoS, Kiyama H, Iwata H, Tomita T, Iwatsubo T, Saido TC: "Neprilysin degrades both amyloid b peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan-and phosphoramidon-sensitive endopeptidases"J. Biol Chem. 276. 21895-21901 (2001)
• [Publications] Abe K, Namikawa K, Honma M, Iwata T, Matsuoka I, Watabe K, Kiyama H: "Inhibition of Ras-Extracellular signal-regulated Kinase (ERK) mediated signaling promotes ciliary neurotrophic factor (CNTF) expression in schwann cells"J. Neurochem. 77(2). 700-703 (2001)
• [Publications] Uchino,S.Nakamura,T.Makamura,K.,N-Iijima,S.,Mishina,M.Kohsaka,S.& Kudo,Y.: "A Real time, two demensional visualrization of ischemia-induced glutamate release from hippocampal slices"Europ.J.Neurosci.. 13(4). 670-678 (2001)
• [Publications] Kojima,H.,Hirata,M.,Kudo,Y.,Kikuchi,K & Nagano,T.: "Visualization of Oxygen Concentration-dependent Production of Nitric Oxide in Rat Hippocampal Slices during Aglycemia"J.Neurochem. 76. 1-8 (2001)
• [Publications] Nakagomi S,Kiryu-Seo S,Kiyama H: "Endoothelin converting enzymes and endothelin receptor B mRNAs are expressed in different neural cell species and these mRNAs are coordinately induced in neurons and astrocytes respectively."Neuroscience. 101. 441-449 (2000)
• [Publications] Tanabe K,Tachibana T,Yamashita T,Che YH,Yoneda Y,Ochi T,Tohyama M,Yoshikawa T,Kiyama H: "The small GTP-binding protein TC10 promotes growth cone-like formation and nerve elongation in neuronal cells, and its expression is induced during nerve regeneration in rats."J.Neurosci.. 20. 4138-4144 (2000)
• [Publications] Namikawa,K.,Honma,M.,Abe,K.,Takeda,M.,Mansur,K.,Obata,T.,Miwa,A.,.Okada,H.and Kiyama,H: "Akt/PKB prevents injury-induced motor neuron death and accelates axonal regenaration"J.Neuroscience. (in press). (2000)
• [Publications] Takano,R.,Hisahara,S.,Namikawa,K.,Kiyama,H.,Okano H,Miura M: "Nervegrowth factor protects oligodendrocytes from TNF-a-induced injury through Akt-mediated signaling mechanisms."J.Biol.Chem.. 275. 16360-16365 (2000)
• [Publications] Hirasawa, T. , Nakamura, T. , Mizushima, A. , Morita, M. , Ezawa, I. , Miyakawa, H. & Kudo, Y.: "Adverse effects of an active fragment of parahyroid hormone on rat hippocampal organotypic cultures"Brit. J. Pharmacol.. 129. 21-28 (2000)
• [Publications] Kojima, S. , Nakamura, T. , Nidaira, T. , Nakamura, K. , OOashi, N. , Ito, E. , Watase, K. , Tanaka, K. , Wada, K. , Kudo, Y. & Miyakawa, H.: "Optical detection of synaptically induced glutamate transport in hippocampal slices"J. Neuroscience. 19(7). 2580-2588 (1999)
• [Publications] Tanabe, K. , nakagomi, S. , Kiryu-Seo, S., Namikawa, K. , Imai, Y. , Ochi, T. , Tohyama, M. , Kiyama: "Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy"Mol. Brain Res.. 65. 34-40 (1999)
• [Publications] Kiryu-Seo, S. , Sakaki, M. , Yokohama, H. , Nakagomi, S. , Hirayama, T. , Aoki, S. , Wada, K. and Kiyama, H.: "Damage induced neuroral endopeptidase(DINE) as a unique metallopeptidase expressed in response to neuronal damage and active superoxide scavengers"Proc. Natl. Acad. Sci. USA. (in press). (2000)
• [Publications] Namikawa, K. , Honma, M. , Abe, K. , Takeda, M. , Mansur, K. , Obata, T. , Miwa, A. , Okada, H. and Kiyama, H.: "Akt/PKB prevents injury-induced motor neuron death and accelates axonal regenaration"J. Neuroscience. (in press). (2000)
• [Publications] 工藤佳久: "グリア研究の歴史と現状"Clinical Neuroscience. 17(9). 970-974 (1999)
• [Publications] Sekiguchi, M., Takeo, J., Harada, T., Morimoto, T., Kudo, Y., Yamashita, S., Kohsaka, S. and Wada, K.: "Pharmacological detection of AMPA receptor heterogeneity by use of two allosteric potentiators in rat hippocampal cultures." Brit. J.Pharmacol.123. 1294-1303 (1998)
• [Publications] Kojima, S., Nakamura, T., Nidaira, T., Nakamura, K., OOashi, N. Ito,E., Watase, K., Tanaka, K., Wada, K., Kudo, Y., & Miyakawa, H.: "Optical detection of synaptically induced glutamate transport in hippocampal slices" J. Neuroscience. 19. 印刷中(9頁) (1999)
• [Publications] Tanabe K, Nakagomi S, Kiryu-Seo S, Namikawa K, Imai Y, Ochi T, Tohyama M, Kiyama: "Expressed-sequence-tag approach to identify differentially expressed genes following peripheral nerve axotomy." Mol. Brain Res.64. 34-40 (1999)
• [Publications] 森田光洋、工藤佳久: "グリア細胞の性質と機能" 生物物理. (印刷中)