NRG1/ErbB4通过GABA能系统抑制外侧杏仁核的LTP
发布时间：2020-12-13 19:59
精神分裂症是一种严重危害人类健康的精神疾病,它影响着全世界约1%的人口。Neuregulin1 （NRG1）与ErbB4作为精神分裂症众多易感基因中的一员,在近年来正在被越来越多的人重视并已成为神经科学研究的热点之一。在冰岛、苏格兰、爱尔兰、中国和韩国等人群的分子遗传学研究结果表明NRG1和ErbB4是精神分裂症的易感基因。在精神分裂症患者的脑中也发现有NRG1或ErbB4表达量的异常增加,且患者大脑皮质中NRG1激活的ErbB4活性也有升高。再者,NRG1或ErbB4的敲除小鼠也表现出类精神分裂症样的症状。Neuregulin是一类隶属于营养因子家族的多肽因子,其由NRG基因编码产物的选择性剪切体所组成。在NRG的多种异构体当中（NRG 1-4）,对NRG1的研究最为广泛。NRG1通过ErbB受体酪氨酸激酶起作用,ErbB受体同样具有多种异构体（ErbB1-4）。其中ErbB4在脑内高表达,并与NRG1结合后可激活其酪氨酸激酶的活性。NRG1-ErbB4信号通路在神经系统的发育中发挥着重要的作用,并且以往的研究大都集中于此。现已发现它参与了神经细胞的分化、神经元的迁移、神经突起的外向...
【文章来源】：南方医科大学广东省
【文章页数】：94 页
【学位级别】：博士
【文章目录】：
中文摘要
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
Reagents and Animals
Cell Culture and Ecto-ErbB4 Purified
Slice Preparation
Electrophysiological recording
Western blot analysis
Statistical analysis
RESULTS
1. Amygdala exhibits comparatively high GABAergic activity
2. LTP in LA is suppressed in normal conditions with compare to CA1, and thissuppression is removed by BMI
3. NRG1-ErbB4 signaling inhibitor attenuates GABAA receptor-mediated synapticcurrents while its enhancer has no effects
4. Both thalamus and cortex input LTP was induced in LA after perfusion ofEcto-ErbB4
5. Perfusion of ecto-ErbB4 do not further increase the extent of LTP in slicesGABA-mediated inhibition have been blocked
6. ecto-ErbB4 treatment show normal basal synaptic transmission in LA
7. ErbB4-/-HER4heart mice identification
8. Changes in the balance of excitation and inhibition of ErbB4-/-HER4heart mice
-/-HER4heart mice exhibited LTP in LA"> 9. ErbB4-/-HER4heart mice exhibited LTP in LA
DISCUSSION
1. LA exhibits robust GABAergic inhibiton with compare to other brain areas
2. Block NRG1-ErbB4 signaling decreases the GABAergic inhibiton in the lateralamygdala
3. NRG1/ErbB4 signaling contributes to the suppression of LTP in the lateralamygdala
4. Blocking GABAA recepotor prevents suppression of LTP induction in the LA
SUMMARY
REFERENCE
缩写词表 ABBREVIATIONS
致谢
统计学证明
本文编号：2915099
【文章来源】：南方医科大学广东省
【文章页数】：94 页
【学位级别】：博士
【文章目录】：
中文摘要
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
Reagents and Animals
Cell Culture and Ecto-ErbB4 Purified
Slice Preparation
Electrophysiological recording
Western blot analysis
Statistical analysis
RESULTS
1. Amygdala exhibits comparatively high GABAergic activity
2. LTP in LA is suppressed in normal conditions with compare to CA1, and thissuppression is removed by BMI
3. NRG1-ErbB4 signaling inhibitor attenuates GABAA receptor-mediated synapticcurrents while its enhancer has no effects
4. Both thalamus and cortex input LTP was induced in LA after perfusion ofEcto-ErbB4
5. Perfusion of ecto-ErbB4 do not further increase the extent of LTP in slicesGABA-mediated inhibition have been blocked
6. ecto-ErbB4 treatment show normal basal synaptic transmission in LA
7. ErbB4-/-HER4heart mice identification
8. Changes in the balance of excitation and inhibition of ErbB4-/-HER4heart mice
-/-HER4heart mice exhibited LTP in LA"> 9. ErbB4-/-HER4heart mice exhibited LTP in LA
DISCUSSION
1. LA exhibits robust GABAergic inhibiton with compare to other brain areas
2. Block NRG1-ErbB4 signaling decreases the GABAergic inhibiton in the lateralamygdala
3. NRG1/ErbB4 signaling contributes to the suppression of LTP in the lateralamygdala
4. Blocking GABAA recepotor prevents suppression of LTP induction in the LA
SUMMARY
REFERENCE
缩写词表 ABBREVIATIONS
致谢
统计学证明
本文编号：2915099
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