权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study of neurotransmitters in the brain of SNAP25 mutant mouse.

SNAP25突变小鼠脑内神经递质的研究。

基本信息

批准号：
17591233
负责人：
SUZUKI Eiji
金额：
$ 2.24万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591233/
关键词：
SNAP25 dopamine serotonin mouse behavior SNAP オープンフィールド明暗刺激試験

项目摘要

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. SNAP-25 may also be involved in neurite extension and the regulation of ion channel function. Previously, we demonstrated that protein kinase C (PKC) phosphorylated Ser187 of SNAP-25 and enhanced neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. In order to know the physiological roles of PKC-dependent phosphorylation of SNAP-25 in brain function, we generated a mutant mouse having a substitution of Ser187 with Ala using "knock in" technology. We found that the homozygous mutant mice showed various abnormal behavior such as strong thigmotaxis, hyperlocomotion or freezing-like behavior. In the present study, firstly, we examined levels of neurotransmitters in homogenized samples of various brain regions, thalamus, hypothalamus, amygdala, cortex, hippocampus, cerebellum, brain stem and striatum. The amino acids measured in this study were glutamate, glycine, taurine, arginine and gamma aminobutyric acid (GABA). The monoamines measured were norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3-methoxy-4-hydroxyphenylglycol (MHPG), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). We found that the significant decrease of levels of NE in the amygdala and hippocampus. Next, we investigated the differences of responses of DA and 5-HT to high-potassium stress in the amygdale and restraint stress in the hypothalamus. Under short-time high-potassium stress, there were no significant differences in DA or 5-HT responses between homo and wild mouse, however, under the long-term stress, the responses of DA in homo mouse were significantly weak in comparison with those in wild mouse. We also found that restraint stress induced increases of dopamine and 5-HT in the hypothalamus. DA response was significantly weak in homo mouse in comparison with wild type.

25 kDa 的突触体相关蛋白 (SNAP-25) 是神经递质释放所必需的突触前蛋白。 SNAP-25 还可能参与神经突延伸和离子通道功能的调节。此前，我们证明蛋白激酶 C (PKC) 磷酸化 SNAP-25 的 Ser187，并通过募集质膜附近的分泌囊泡来增强神经递质释放。为了了解 SNAP-25 的 PKC 依赖性磷酸化在脑功能中的生理作用，我们使用“敲入”技术生成了 Ser187 被 Ala 取代的突变小鼠。我们发现纯合突变小鼠表现出各种异常行为，如强烈的趋触性、过度运动或冻结样行为。在本研究中，首先，我们检查了不同脑区、丘脑、下丘脑、杏仁核、皮质、海马、小脑、脑干和纹状体的均质样本中神经递质的水平。本研究中测量的氨基酸是谷氨酸、甘氨酸、牛磺酸、精氨酸和γ-氨基丁酸(GABA)。测量的单胺是去甲肾上腺素（NE）、多巴胺（DA）、血清素（5-HT）、3-甲氧基-4-羟基苯基乙二醇（MHPG）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）和5-羟基吲哚乙酸（5-HIAA）。我们发现杏仁核和海马中的NE水平显着下降。接下来，我们研究了 DA 和 5-HT 对杏仁核高钾应激和下丘脑约束应激反应的差异。在短时高钾胁迫下，纯种小鼠和野生小鼠的DA或5-HT反应没有显着差异，但在长期胁迫下，纯种小鼠的DA反应明显弱于野生小鼠。我们还发现，束缚应激会导致下丘脑中多巴胺和 5-HT 的增加。与野生型相比，纯种小鼠的 DA 反应明显较弱。