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Role of glial cells in brain development

神经胶质细胞在大脑发育中的作用

基本信息

批准号：
14208092
负责人：
TANAKA Kohichi
金额：
$ 24.04万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14208092/
关键词：
neuroscience brain and neuron development and differentiation glutamate knockout mice glial cells

项目摘要

1.Role of glia glutamate transporters in brain developmentPrevious 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 astrocyteWe 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 channel3.Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytesNeuron-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

1.神经递质谷氨酸在脑发育中的作用先前的体外研究表明，谷氨酸在中枢神经系统发育中起重要作用。矛盾的是，谷氨酸能信号丧失的小鼠模型显示大脑组装正常。我们通过靶向删除谷氨酸转运体GLAST和GLT1来增加谷氨酸受体的激活，从而建立了谷氨酸能信号传导的功能获得模型。GLAST/GLT1双敲除小鼠表现出多种脑缺陷，包括皮质、海马和嗅球紊乱。这些结果提供了直接的体内证据，表明GLAST和GLT1通过调节细胞外谷氨酸浓度来控制大脑发育，谷氨酸除了作为神经递质外，在大脑发育中也起着关键作用。星形胶质细胞钙自发振荡的机制我们正在研究星形胶质细胞钙自发振荡的控制机制及其与神经活动的关系。我们发现，谷氨酸通过谷氨酸转运体触发Na离子的进入，进而激活电压门控的Ca通道3。神经胶质谷氨酸转运体介导神经元和星形胶质细胞之间的功能性代谢串音。神经元-胶质相互作用对突触功能至关重要，胶质谷氨酸再摄取在谷氨酸能突触中起关键作用。在神经胶质谷氨酸转运体（GLAST或GLT-1）的敲除小鼠中，在须激活后的早期功能阶段，体感桶状皮层对突触激活的经典代谢反应（即葡萄糖利用的增强）减少。体外研究表明，胶质谷氨酸转运是触发葡萄糖利用增强的关键步骤，也是通过细胞内Na^+浓度变化的机制触发星形胶质细胞释放乳酸的关键步骤。这些数据表明，在发育中的皮层中，神经元和星形胶质细胞之间发生了代谢串扰，该串扰受突触活动的调节和胶质谷氨酸转运体的介导。少

项目成果

期刊论文数量（53）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chen W.: "The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons."Journal of Neuroscience. 24. 1136-1148 (2004)

Chen W.：“谷氨酸转运蛋白 GLT1a 在成熟海马神经元的兴奋性轴突末端表达。”神经科学杂志。

DOI：
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0
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Huang YH.: "Climbing fiber activation of EAAT4 transporters and kainite receptors in cerebellar Purkinje cells."Journal of Neuroscience. 24. 103-111 (2004)

Huang YH.：“小脑浦肯野细胞中 EAAT4 转运蛋白和红藻氨酸受体的攀爬纤维激活。”神经科学杂志。

DOI：
发表时间：
期刊：
影响因子：
0
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Glial Glutamate Transporters Mediate a Functional Metabolic Crosstalk between Neurons and Astrocytes in the Mouse Developing Cortex

DOI：
10.1016/s0896-6273(02)01170-4
发表时间：
2003-01
期刊：
Neuron
影响因子：
16.2
作者：
Brigitte Voutsinos-Porche;G. Bonvento;Kohichi Tanaka;P. Steiner;E. Welker;J. Chatton;P. Magistretti;L. Pellerin
通讯作者：
Brigitte Voutsinos-Porche;G. Bonvento;Kohichi Tanaka;P. Steiner;E. Welker;J. Chatton;P. Magistretti;L. Pellerin

Distributions of two chicken bonbesin receptors, bombesin receptor subtype-3.5 (chBRS-3.5) and gastrin-releasing peptide receptor (chGRP-R) mRNA's in chicken telencephalon.

鸡端脑中两种鸡铃蟾肽受体、铃蟾肽受体亚型 3.5 (chBRS-3.5) 和胃泌素释放肽受体 (chGRP-R) mRNA 的分布。