| 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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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥37,570,000 (Direct Cost: ¥28,900,000、Indirect Cost: ¥8,670,000)
Fiscal Year 2004: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2003: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2002: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
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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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