發(fā)布時間：2020-12-13 19:59

　　精神分裂癥是一種嚴重危害人類健康的精神疾病,它影響著全世界約1%的人口。Neuregulin1 （NRG1）與ErbB4作為精神分裂癥眾多易感基因中的一員,在近年來正在被越來越多的人重視并已成為神經(jīng)科學研究的熱點之一。在冰島、蘇格蘭、愛爾蘭、中國和韓國等人群的分子遺傳學研究結(jié)果表明NRG1和ErbB4是精神分裂癥的易感基因。在精神分裂癥患者的腦中也發(fā)現(xiàn)有NRG1或ErbB4表達量的異常增加,且患者大腦皮質(zhì)中NRG1激活的ErbB4活性也有升高。再者,NRG1或ErbB4的敲除小鼠也表現(xiàn)出類精神分裂癥樣的癥狀。Neuregulin是一類隸屬于營養(yǎng)因子家族的多肽因子,其由NRG基因編碼產(chǎn)物的選擇性剪切體所組成。在NRG的多種異構(gòu)體當中（NRG 1-4）,對NRG1的研究最為廣泛。NRG1通過ErbB受體酪氨酸激酶起作用,ErbB受體同樣具有多種異構(gòu)體（ErbB1-4）。其中ErbB4在腦內(nèi)高表達,并與NRG1結(jié)合后可激活其酪氨酸激酶的活性。NRG1-ErbB4信號通路在神經(jīng)系統(tǒng)的發(fā)育中發(fā)揮著重要的作用,并且以往的研究大都集中于此�，F(xiàn)已發(fā)現(xiàn)它參與了神經(jīng)細胞的分化、神經(jīng)元的遷移、神經(jīng)突起的外向... 

【文章來源】：南方醫(yī)科大學廣東省

【文章頁數(shù)】：94 頁

【學位級別】：博士

【文章目錄】：
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
-/-HER4^heart mice exhibited LTP in LA">    9. ErbB4^-/-HER4^heart 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
縮寫詞表 ABBREVIATIONS
致謝
統(tǒng)計學證明



本文編號：2915099