本文關(guān)鍵詞：杏仁外側(cè)核突觸可塑性在抑郁癥發(fā)病中的作用及機(jī)制研究　出處：《山東大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 抑郁癥 突觸可塑性 慢性不可預(yù)知性溫和應(yīng)激刺激 杏仁外側(cè)核 姜黃素 腦源性神經(jīng)生長(zhǎng)因子

【摘要】：背景抑郁癥是危害人類健康的常見神經(jīng)精神性疾患,其病理機(jī)制迄今尚未徹底闡明。積累的證據(jù)顯示抑郁癥患者邊緣系統(tǒng)的部分腦區(qū)出現(xiàn)結(jié)構(gòu)、功能的改變,提示環(huán)境應(yīng)激因素對(duì)邊緣系統(tǒng)突觸可塑性的影響在抑郁癥的形成過(guò)程中起重要作用。杏仁核是邊緣系統(tǒng)的重要結(jié)構(gòu),參與恐懼記憶的形成和消退。本研究在成功建立大鼠抑郁癥模型的基礎(chǔ)上,結(jié)合形態(tài)、分子生物學(xué)和行為學(xué)的技術(shù)手段研究了杏仁外側(cè)核突觸可塑性與抑郁行為形成的關(guān)系,同時(shí)探討了姜黃素抗抑郁效應(yīng)的機(jī)制。目的1.應(yīng)用慢性不可預(yù)知性溫和應(yīng)激刺激(CUMS)建立大鼠抑郁癥模型,研究抑郁行為和杏仁外側(cè)核突觸可塑性的關(guān)系。2.使用上述抑郁癥模型探討姜黃素的抗抑郁效應(yīng)及其作用機(jī)制。方法將Wistar大鼠隨機(jī)分為空白對(duì)昭、CUMS、姜黃素處理和溶劑對(duì)照四組。除空白對(duì)照組外,CUMS組,姜黃素處理組和溶劑對(duì)照組的動(dòng)物均接受為期6周的慢性不可預(yù)知性溫和應(yīng)激刺激。姜黃素處理組在每次施予刺激前30分鐘給予姜黃素腹腔注射,溶劑對(duì)照組給予姜黃素溶劑DMSO腹腔內(nèi)注射。刺激完畢后對(duì)大鼠進(jìn)行曠場(chǎng)實(shí)驗(yàn)、強(qiáng)迫游泳實(shí)驗(yàn)和糖水偏好實(shí)驗(yàn)等行為學(xué)測(cè)試。應(yīng)用透射電子顯微鏡觀察杏仁外側(cè)核(LA)神經(jīng)元超微結(jié)構(gòu)。取杏仁外側(cè)核組織進(jìn)行免疫印跡和免疫熒光測(cè)定,觀察BDNF、PSD-95和突觸小泡蛋白(synaptophysin)表達(dá)水平的變化。用ERK阻斷劑SL327預(yù)處理姜黃素組大鼠,觀察對(duì)LA神經(jīng)元及抑郁行為的影響,從而探討姜黃素在抑郁癥發(fā)生中的機(jī)制。結(jié)果(1)與空白對(duì)照組相比,CUMS組大鼠體重增加變緩,曠場(chǎng)實(shí)驗(yàn)中橫向運(yùn)動(dòng)和縱向運(yùn)動(dòng)均明顯減少,強(qiáng)迫游泳實(shí)驗(yàn)中靜止時(shí)間顯著增長(zhǎng)而游泳時(shí)間變短,糖水偏好實(shí)驗(yàn)中糖水消耗量明顯減少。(2)電鏡結(jié)果顯示CUMS組大鼠杏仁外側(cè)核神經(jīng)元出現(xiàn)核固縮和細(xì)胞器排列散亂等異常改變,而且出現(xiàn)突觸數(shù)目減少以及突觸前后膜變薄等突觸結(jié)構(gòu)變化。(3)免疫熒光和免疫印跡結(jié)果顯示,與空白對(duì)照組相比,6周CUMS刺激導(dǎo)致LA部位的BDNF、PSD-95和synaptophysin的表達(dá)減少。(4)與CUMS組相比,姜黃素改善了大鼠的體重增長(zhǎng)以及橫向運(yùn)動(dòng)和縱向運(yùn)動(dòng),同時(shí)減少了強(qiáng)迫游泳實(shí)驗(yàn)中的靜止時(shí)間并增加了游泳時(shí)間,而且糖水消耗量也有明顯增加。。免疫熒光和免疫印跡結(jié)果顯示姜黃素治療組LA部位BDNF、PSD-95和synaptophysin的表達(dá)水平均高于CUMS組動(dòng)物。(5)另外,姜黃素的抗抑郁作用還伴隨杏仁外側(cè)核神經(jīng)元磷酸化ERK1/2的表達(dá)水平的提高。結(jié)論1.CUMS誘導(dǎo)大鼠產(chǎn)生抑郁樣行為并伴隨杏仁外側(cè)核神經(jīng)元的突觸可塑性改變。2.這一可塑性改變可能與CUMS下調(diào)ERK磷酸化水平,減少BDNF蛋白表達(dá),從而影響了突觸相關(guān)蛋白如PSD-95和synaptophysin的蛋白表達(dá)有關(guān)。3.姜黃素可通過(guò)ERK-BDNF調(diào)節(jié)神經(jīng)突觸可塑性變化,發(fā)揮其抗抑郁效應(yīng)。
[Abstract]:Background depression is a common disease of nervous and mental harm to human health, the pathological mechanism has not been completely elucidated. The accumulation of evidence of brain structure in patients with depression of the limbic system, functional changes, suggesting the influence environmental stress factors on the plasticity of synaptic limbic system can play an important role in the formation process of depression in the amygdala. Is an important structure of the limbic system, the formation and extinction of fear memory. In the foundation of the establishment of rat model of depression in the success, combined with the form, the relationship between technology in molecular biology and behavior of the lateral amygdaloid nucleus of synaptic plasticity and depressive behavior formation, and discuss the mechanism of antidepressant effect of curcumin 1.. Application of chronic unpredictable mild stress (CUMS) to establish rat model of depression, depression and behavior of lateral amygdaloid nucleus synapses can be The plastic of the relation.2. to explore the use of the model of depression with antidepressant effect of curcumin and its mechanism. Methods: Wistar rats were randomly divided into the blank of Zhao, CUMS, curcumin and four solvent control group. Except the blank control group, CUMS group, curcumin treatment group and solvent control group animal were treated for a period of 6 weeks of chronic unpredictable mild stress. Curcumin administered 30 minutes before stimulation of curcumin intraperitoneal injection in each solvent control group received intraperitoneal injection of curcumin in DMSO solvent. After the stimulation of open field experiments on rats, the forced swimming test and sucrose preference test were studied by transmission electron testing. Microscope observation of lateral amygdaloid nucleus (LA) neurons. The ultrastructure of lateral amygdaloid nucleus tissue were observed by Western blot and immunofluorescence assay of BDNF, PSD-95, and synaptophysin (synaptophysin) The expression of inhibitor of SL327 pretreatment of curcumin. The rats in group ERK, observe the effect on LA neurons and depressive behavior, and to explore the mechanism of curcumin in occurrence of depression. Results (1) compared with the control group, CUMS group rats weight increased slowly, open field test and real transverse motion the vertical movement decreased immobility time during the forced swimming test increased significantly while swimming time, reduce the consumption of sucrose sucrose preference test. (2) electron microscope showed that CUMS rats lateral amygdaloid nucleus neurons karyopyknosis and organelles arranged scattered abnormal changes, and reduce the number of synapses and synaptic before and after the changes of membrane thinning of synaptic structure. (3) immunofluorescence and Western blot results showed that compared with the control group, 6 weeks stimulation with CUMS resulted in LA position of BDNF, PSD-95 and synaptophysin expression decreased (4) and CU. Compared with the MS group, curcumin improved the body weight gain of rats and the horizontal and vertical movement, and reduce the immobility time during the forced swimming test and the increase of the swimming time, and sugar consumption have increased significantly. Immunofluorescence and Western blotting showed Jiang Huang in treatment of BDNF group at the LA expression level of PSD-95 and synaptophysin the animal was higher than that in group CUMS (5). In addition, the antidepressant effects of curcumin with the expression level of lateral amygdaloid nucleus on the expression of phosphorylated ERK1/2 increased. Conclusion 1.CUMS induce depression like behavior and associated with synaptic plasticity with lateral amygdaloid nucleus neurons change.2. this plasticity may be associated with downregulation of CUMS ERK the phosphorylation level, decrease the expression of BDNF protein, thus affecting the synapse associated proteins such as PSD-95 and synaptophysin on the expression of.3. ERK-BDNF by curcumin can regulate the nerve The synaptic plasticity changes and plays its antidepressant effect.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R749.4

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本文編號(hào)：1397641