2004 Fiscal Year Final Research Report Summary
Role of glial cells in brain development
| Project/Area Number |
14208092
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TANAKA Kohichi Tokyo Medical and Dental University, School of Miomedical Science, Professor, 大学院・疾患生命科学研究部, 教授 (80171750)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Takashi Senshu University, School of Literature, Associate Professor, 文学部, 助教授 (00242082)
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| Project Period (FY) |
2002 – 2004
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| Keywords | neuroscience / brain and neuron / development and differentiation / glutamate / knockout mice / glial cells |
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| Research Abstract |
1.Role of glia glutamate transporters in brain development
Previous in vitro studies demonstrated that the neurotransmitter glutamate is importantly involved in CNS development. Paradoxically, loss-of-function mouse models of glutamatergic signaling show normal brain assembly. We created a gain-of-function model of glutamatergic signaling by increasing glutamate receptor activation through targeted deletion of glutamate transporters GLAST and GLT1. GLAST/GLT1 double knockout mice display multiple brain defects, including cortical, hippocampal and olfactory bulb disorganization. These results provide direct in vivo evidence that GLAST and GLT1 control brain development through the regulation of extracellular glutamate concentration and that glutamate, in addition to its role as neurotransmitter, is a key player in brain development.
2.Mechanisms of spontaneous calcium oscillation in astrocyte
We are studying mechanisms controlling calcium spontaneous transients in astrocytes and their rela
… More
tionship to neural activity. We found that via glutamate transporters, glutamate triggers an entry of Na ions wich in turn activate voltage gated Ca channel
3.Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes
Neuron-glia interactions are essential for synaptic function and glial glutamate reuptake plays a key role at glutamatergic synapses. In knockout mice for either glial glutamate transporters, GLAST or GLT-1, a classical metabolic response to synaptic activation (i.e. enhancement of glucose utilization) is decreased at an early functional stage in the somatosensory barrel cortex following activation of whiskers. Investigation in vitro demonstrates that glial glutamate transport represents a critical step for triggering enhanced glucose utilization but also lactate release from astrocytes through a mechanism involving changes in intracellular Na^+ concentration. These data suggest that a metabolic crosstalk takes place between neurons and astrocytes in the developing cortex which would be regulated by synaptic activity and mediated by glial glutamate transporters. Less
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[Journal Article] Role of Neurotrophin-4/5 in Neural Cell Death during Retinal Development and Ischemic Retinal Injury in Vivo.2005
Author(s)
Harada, C., Harada, T., Quah, H-M A., Namekata, K., Yoshida, K., Ohno, S., Tanaka K., Parada, L.F.
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Journal Title
Invest Ophthalmol Vis Sci 46
Pages: 669-673
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glutamate transporter in retinal Muller cells from glutamate/aspartate transporter (GLAST) knockout mice.2005
Author(s)
Sarthy, V.P., Pignataro, L., Pannicke, T., Weick, M., Reichenbach, A., Harada, T., Tanaka K., Marc, R.
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Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons.2004
Author(s)
Chen, W., Mahadomrongkul, V., Berger, U.V., Bassan, M., DeSilva, T., Tanaka K., Irwin, N., Aoki, C., Rosenberg, P.A.
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Journal Title
J.Neurosci. 24
Pages: 1136-1148
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Diverse NF-kB expression in epiretinal membranes after human diabetic retinopathy and proliferative vitreoretinopaty.2004
Author(s)
Harada, C., Harada, T., Mitamura, Y., Quah, H-M.A., Ohtsuka, K., Kotake, S., Ohno, S., Wada, K., Takeuchi, S., Tanaka K.
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Journal Title
Mol.Vision 10
Pages: 31-36
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced by ischemic retinal injury in vivo.2004
Author(s)
Harada, T., Harada, C., Wang, Y-U., Osaka, H., Amanai, K., Tanaka K., Takizawa, S., Setsuie, R., Sakurai, M., Sato, Y., Noda, M., Wada, K.
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Journal Title
Am.J.Pathol. 164
Pages: 59-64
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Potential role of glial cell line-derived neurotrophic factor receptors in Muller glial cells during light-induced retinal degeneration.2003
Author(s)
Harada, C., Harada, T., Quah, H.-M.A., Maekawa, F., Yoshida, K., Ohno, S., Wada, K., Parada, L.F., Tanaka, K.
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Journal Title
Neuroscience 122
Pages: 229-235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glial glutamate transporters and maturation of the mouse somatosensory cortex.2003
Author(s)
Voutsinos-Porche, B., Knott, G., Tanaka, K., Quairiaux, C., Welker, E., Bonvento, G.
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Journal Title
Cereb.Cortex 13
Pages: 1110-1121
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular cloning and characterization of avian bombesin-like peptide receptors : New tools for investigating molecular basis for ligand selectivity.2003
Author(s)
Iwabuchi, M., Ui-Tei, K., Yamada, Y., Matsuda, Y., Sakai, Y., Tanaka.K., Ohki-Hamazaki, H.
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Journal Title
Brit.J.Pharmacol. 139
Pages: 555-566
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] NF-kB in epiretinal membranes after human diabetic retinopathy.2003
Author(s)
Mitamura, Y., Harada, T., Harada, C., Ohtsuka, K., Kotake, S., Ohno, S., Tanaka, K., Takeuchi, S., Wada, K.
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Journal Title
Diabetologia 46
Pages: 699-703
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Long-term potentiation in the hippocampal CA1 area and dentate gyrus plays different roles in spatial learning.2003
Author(s)
Okada, T., Yamada, N., Tsuzuki, K., Horikawa, PM., Tanaka, K., Ozawa, S.
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Journal Title
Eur.J.Neurosci. 17
Pages: 341-349
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex.2003
Author(s)
Voutsinos-Porche, B., Bonvento, G., Tanaka.K., Welker, E., Chatton, J.-Y., Magistretti, P.J., Pellerin, L.
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Description
「研究成果報告書概要(欧文)」より
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