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Roles of brain mast cells and their related substances in the central mechanisms of stress responses

脑肥大细胞及其相关物质在应激反应中枢机制中的作用

基本信息

批准号：
10557008
负责人：
KATAFUCHI Toshihiko
金额：
$ 7.55万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10557008/
关键词：
c-kit stem cell factor spatial learning and memory mutant rat mossy fiber-CA3 pathway tetanic stimulation long-term potentiation real-time RT-PCR 肥満細胞増殖因子 c-kit mRNA リアルタイムPCR テタヌス刺激海馬スライス隔離ストレス c-kitミュータントラットシナプス可塑性 Pai

项目摘要

It is well known that a variety of cytokines, growth factors and cell adhesion molecules are synthesised in the brain, and affect the neuronal activities, thereby playing a role in the mechanisms of homeostasis and stress responses. Receptor tyrosine kinase, c-kit, is expressed in mast cells and their precursor cells, and involved in the differentiation and proliferation of mast cells by the action of its ligand, stem cell factor (SCF). However, recent anatomical studies have shown that both c-kit and SCF are found in the hippocampus of the adult rat and mouse. In the present study, therefore, we investigated a role of c-kit/SCF signaling in learning and memory, and found the following results.(1) The homozygous (Ws/Ws)mutant rats, that have deletion of 4 amino acids in the tyrosine kinase domain of c-kit receptors and a very low kinase activity, shown a deficit in spatial learning and memory in Morris water maze.(2) The c-kit mutant rats also demonstrated an impariment of paired-pulse … More facilitation (PPF) and the tetanus-induced long-term potentiation (LTP) in the hippocampal mossy fiber (MF)-CA3 pathway but not in the Schaffer collateral/commissural (S/C)-CA1 pathway.(3) When recombinant mouse SCF was applied to the hippocampal slices of normal mice, SCF acted on the postsynaptic c-kit receptors, then activated PI3'-kinase and phospholipased A2, As a result, PPF in the MF-CA3 pathway was affected as it was after the establishment of LTP.It is considered that arachidonic acid plays a role as a retrograde neurotransmitter in the action of SCF.(4) In mouse slice preparations, the contents of SCF and c-kit mRNA were decreased after the tenic stimulation was applied to the MF-CA3 pathway. The quantitative measurement of mRNA levels were performed by a real-time capillary RT-PCR method.(5) The amount of SCF and c-kit mRNA in the mouse brain decreased after 8 days isolation stress.Thus it is concluded that c-kit/SCF signaling plays a significant role in the hippocampal synaptic potentiation and learning and memory in adult animals and that stressful stimuli affected the expression of SCF amd c-kit mRNA, which may result in the impairment of learing and memory during stress responses. Less

众所周知，脑内合成多种细胞因子、生长因子和细胞粘附分子，影响神经元的活动，从而在体内平衡和应激反应机制中发挥作用。受体酪氨酸激酶c-kit在肥大细胞及其前体细胞中表达，并通过其配体干细胞因子（SCF）的作用参与肥大细胞的分化和增殖。然而，最近的解剖学研究表明，c-kit和SCF都发现在成年大鼠和小鼠的海马。因此，在本研究中，我们研究了c-kit/SCF信号在学习和记忆中的作用，并发现了以下结果。(1)C-kit受体酪氨酸激酶区缺失4个氨基酸且激酶活性极低的纯合子（Ws/Ws）突变大鼠在Morris水迷宫中表现出空间学习和记忆的缺陷。(2)c-kit突变大鼠也表现出成对脉冲的不对称性 ...更多信息在海马苔藓纤维（MF）-CA 3通路中存在强直诱发的长时程增强（LTP），但在Schaffer侧支/连合（S/C）-CA 1通路中不存在。(3)将重组小鼠SCF作用于正常小鼠海马脑片，SCF作用于突触后c-kit受体，激活PI 3 '-激酶和磷脂酶A2，导致MF-CA 3通路中的PPF在LTP建立后仍受到影响，认为花生四烯酸在SCF的作用中起着逆行神经递质的作用。(4)在小鼠脑片制备中，对MF-CA 3通路施加张力刺激后，SCF和c-kit mRNA的含量降低。通过实时毛细管RT-PCR方法进行mRNA水平的定量测量。(5)结果表明，在8d的隔离应激后，小鼠脑内SCF和c-kit mRNA的表达量明显减少，提示c-kit/SCF信号在成年动物海马突触增强和学习记忆中起重要作用，应激刺激影响SCF和c-kit mRNA的表达，可能是导致应激反应中学习记忆障碍的原因之一。少