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The roles and mechanisms of GABA receptor activation in regulating neurogenesis i

GABA受体激活在调节神经发生中的作用和机制

基本信息

批准号：
8531359
负责人：
Shaoyu Ge
金额：
$ 25.8万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8531359
关键词：
Acids Adult Area Axon Brain Brain Diseases Butyric Acids Cells Confocal Microscopy Data Degenerative Disorder Dendrites Development Disease Electron Microscopy Electrophysiology (science)Embryo Embryonic Development Engineering Epilepsy Etiology Generations Glutamates Hippocampus (Brain)Image Immunohistochemistry Label Laboratories Lead Life Light Mammals Mental disorders Molecular Mus Nature Neuraxis Neuronal Differentiation Neurons Neurotransmitters Newborn Infant Pathology Physiological Play Process Receptor Activation Retroviridae Role Series Staging Stem cells Synapses Techniques adult neurogenesis combinatorial dentate gyrus embryonic stem cell gamma-Aminobutyric Acid granule cell in vivo migration nerve stem cell nervous system disorder neural precursor cell neurodevelopment neurogenesis neuron development newborn neuron novel novel therapeutics progenitor receptor synaptogenesis therapy development two-photon

项目摘要

Neurogenesis was traditionally believed to occur only during embryonic development in mammals. Only recently has it become generally accepted that new neurons are indeed continuously produced and integrated in discrete regions of the adult mammalian central nervous system. Adult neurogenesis recapitulates the complete process of the neuronal development, from fate specification of neural progenitors, migration, synaptic integration and maturation of newborn dentate granule cells (DGCs). The molecular mechanisms that regulate these neurogenesis steps are largely unknown. Gamma-aminbutyric acid (GABA), one of the major inhibitory neurotransmitter in the adult central nervous system, activates GABA receptors in the tonic/phasic mechanisms. Emerging evidence suggests that GABA receptor activity also plays an essential role in regulating the adult neurogenesis. The specific contribution of tonic and/or phasic GABA activation to the proliferation and differentiation of adult neural progenitors and the synaptic integration of their progeny, however, is unknown, and will be examined in our current proposal. Specific Aim I: To determine the roles of tonic GABA receptor activation in regulating proliferation and fate specification of neural progenitors in the adult brain. Specific Aim II: To examine the specific roles of tonic and/or phasic GABA receptor activation in synapse formation and maturation of newborn DGCs in the adult brain. Specific Aim III: To determine the roles of GABA receptor activation in the formation of functional synapses by the axons of newborn DGCs in the adult brain. The approach will be to use engineered retroviruses to genetically manipulate GABAergic activity of the adult neural progenitors and their progeny. The proliferation and differentiation of these genetically-manipulated adult neural progenitors and the synaptic integration of these newborn neurons will be examined. Understanding these regulatory mechanisms for adult neurogenesis may provide clues into the etiology and pathology of these brain disorders and diseases. More importantly, these studies may shed light on novel therapy development such as functional replacement of damaged neurons in degenerative neurological disease utilizing stem cells, including both embryonic stem cells and adult neural stem cells.

传统上认为神经发生只发生在胚胎发育过程中

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neurogenesis and hippocampal plasticity in adult brain.

DOI：
10.1007/7854_2012_217
发表时间：
2013-01-01
期刊：
Current topics in behavioral neurosciences
影响因子：
0
作者：
Gu, Yan;Janoschka, Stephen;Ge, Shaoyu
通讯作者：
Ge, Shaoyu

Optical controlling reveals time-dependent roles for adult-born dentate granule cells.

DOI：
10.1038/nn.3260
发表时间：
2012-12
期刊：
NATURE NEUROSCIENCE
影响因子：
25
作者：
Gu, Yan;Arruda-Carvalho, Maithe;Wang, Jia;Janoschka, Stephen R.;Josselyn, Sheena A.;Frankland, Paul W.;Ge, Shaoyu
通讯作者：
Ge, Shaoyu

A role for primary cilia in glutamatergic synaptic integration of adult-born neurons.