精神分裂癥是一種嚴(yán)重危害人類(lèi)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(lái)正在被越來(lái)越多的人重視并已成為神經(jīng)科學(xué)研究的熱點(diǎn)之一。在冰島、蘇格蘭、愛(ài)爾蘭、中國(guó)和韓國(guó)等人群的分子遺傳學(xué)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(dá)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(lèi)精神分裂癥樣的癥狀。Neuregulin是一類(lèi)隸屬于營(yíng)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(dāng)中（NRG 1-4）,對(duì)NRG1的研究最為廣泛。NRG1通過(guò)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(dá),并與NRG1結(jié)合后可激活其酪氨酸激酶的活性。NRG1-ErbB4信號(hào)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。現(xiàn)已發(fā)現(xiàn)它參與了神經(jīng)細(xì)胞的分化、神經(jīng)元的遷移、神經(jīng)突起的外向... 

【文章來(lái)源】：南方醫(yī)科大學(xué)廣東省

【文章頁(yè)數(shù)】：94 頁(yè)

【學(xué)位級(jí)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(xiě)詞表 ABBREVIATIONS
致謝
統(tǒng)計(jì)學(xué)證明



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