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Intercelluar Bioactive Molecules in Neural Circuit

神经回路中的细胞间生物活性分子

基本信息

批准号：
08044261
负责人：
NAWA Hiroyuki
金额：
$ 2.94万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Neurons communicate with each other using a large variety of neurotransmitters and receptors. Despite this enormous diversity, each functional neural pathway can be recognized by its distinctive set of transmitters and receptors employed. How is the neurotransmitter/peptide phenotype specified in each neural pathway during development? The importance of their phenotypic regulation has been argumented since abnormal expression of neurotransmitters or their receptors are often associated with various neurological diseases.We have previously shown that diffusible intercellular factors such as nerve growth factor can regulate such neuronal phenotypes in cultured neurons. In this proposed project, we aimed at studying their in vivo influences on transmitter/receptor phenotypes using mutant mice whose genes of neurotrophins or related molecules are disrupted. Based on our previous friendship in Cold Spring Harbor Lovoratory, we have established this collaboration project with its neuroscience group to examine a large variety of these mutant mice. We have focused on genes of neurotropic factors as well as their target molecules ; brain-derived neurotrophic factor (BDNF), Fyn, CREB,alpha-CAMK2 and NOS.Molecular, biochemical and histochemical analyzes revealed that the neurotrophin mutant exhibited lower expression of various neurotransmitters, their receptors and the synaptic enzymes, and, in turn, the enzyme mutants contrained abnormal levels of neurotrophins. These observations suggest that neurotrophins and these synaptic receptors/enzymes interact with each other during brain development and regulate synergistic synaptic development.

神经元通过各种神经递质和受体相互交流。尽管存在巨大的多样性，但每个功能性神经通路都可以通过其独特的递质和受体来识别。在发育过程中，神经递质/肽表型在每个神经通路中是如何指定的？由于神经递质或其受体的异常表达往往与各种神经系统疾病有关，因此它们的表型调控的重要性一直受到争论，我们先前已经表明，在培养的神经元中，可扩散的细胞间因子如神经生长因子可以调节这种神经元表型。在这个项目中，我们的目的是研究他们在体内的影响，使用突变小鼠的神经营养因子或相关分子的基因被破坏的递质/受体表型。基于我们之前在冷泉港Lovoratory的友谊，我们与其神经科学小组建立了这个合作项目，以检查大量的这些突变小鼠。我们重点研究了神经营养因子的基因及其靶分子：脑源性神经营养因子（BDNF）、Fyn、CREB、α-CAMK 2和NOS。分子、生物化学和组织化学分析表明，神经营养因子突变体表现出各种神经递质及其受体和突触酶的表达降低，反过来，这些酶突变体抑制了神经营养因子的异常水平。这些观察结果表明，神经营养因子和这些突触受体/酶在大脑发育过程中相互作用，并调节协同突触发育。