Jmjd3通過增強前額葉和海馬神經(jīng)炎癥調控早年應激致抑郁障礙易感性
發(fā)布時間:2021-01-26 16:06
1.研究背景抑郁障礙,是一種最常見的精神疾患,主要癥狀為情緒低落,快感缺失及認知功能損害。研究顯示,抑郁障礙影響世界約4.4%的人口,且因其發(fā)病率和致殘率較高,給社會帶來巨大的經(jīng)濟負擔。但迄今為止,抑郁癥的發(fā)病機理尚未完全闡明,導致治療方法和療效有限。因此,深入探究其發(fā)病機制,尋找新的治療靶點,是抑郁癥防治工作中亟待解決的重要課題。研究顯示,應激是抑郁障礙的重要風險因素,早年應激可以導致大腦結構和功能出現(xiàn)持久性的異常,從而引起個體行為和認知的持久性改變,使個體在成年后抑郁障礙患病易感性增加。大量研究證實,應激可誘導中樞神經(jīng)系統(tǒng)免疫激活,誘發(fā)炎性細胞因子表達失調,進而導致情緒相關腦區(qū)的神經(jīng)炎癥狀態(tài),這一過程是構成抑郁障礙的重要發(fā)病機制之一。小膠質細胞作為中樞神經(jīng)系統(tǒng)中參與固有免疫的神經(jīng)細胞,是炎性細胞因子的主要來源,參與介導神經(jīng)炎癥過程。研究證實,應激狀態(tài)下,下丘腦-垂體-腎上腺(Hypothalamic-pituitary-adrenal,HPA)軸激活,大量糖皮質激素(Glucocorticoid,GC)釋放至調控情緒的腦區(qū)如前額葉、海馬,導致這些區(qū)域小膠質細胞激活。激活的小膠質細胞...
【文章來源】:山東大學山東省 211工程院校 985工程院校 教育部直屬院校
【文章頁數(shù)】:147 頁
【學位級別】:博士
【部分圖文】:
圖1.1實驗范式圖??
?山東大學博士學位論文???A?B??_?100-1?”?100-]??卜n?i?Hi■卜ft?i円i??I-?i|?nl?I-?-I?-i??JJlll?^llJul?JJIJI??///?///?///?///??C?D??40-1?*??一?15.??Iw??J?■*?円???i:ljaMni??/?//?/?//?/,/?/?//??E??0.5-1?*?.??,n;?fi?&?i??i:?n|??::JL?I??/,/?/</??圖1.2青少年期慢性不可預知性應激對青少年和成年大鼠抑郁樣焦慮樣行為的影??響。??Fig.1.2?Effects?of?CUMS?on?the?depressive-?and?anxietj-like?behaviors?of??adolescent?and?adult?rats.?(A)?Sucrose?preference?percentage?in?the?SPT;?(B)??Number?of?crossing?in?the?OFT;?(C)?Number?of?rearing?in?the?OFT;?(D)?Number?of??40??
?山東大學博士學位論文???A?B??*g6-|?^?60-??mAM{Jnl??/?/?/?一?</?/?/?/?/?/?/??圖1.3青少年期慢性不可預知性應激對青少年和成年大鼠空間學習記憶功能的影??響。??Fig.1.3?Effects?of?CUMS?on?the?spatial?learning?and?memory?ability?of?adolescent??and?adult?rats.?(A)?Number?of?crossings?of?the?platform?in?the?MWM?test;?(B)?Target??quadrant?entries?percentage?in?the?MWM?test.?Results?were?expressed?as?the?mean?±??SEM?(n=10?each?group).?#?and?##?indicate?P?<?0.05?and?P?<?0.01?vs.?C?group,??respectively;?and?**?indicate?P?<?0.05?and?P?<?0.01?vs.?S?group,?respectively.??表1-2各組大鼠Morris水迷宮實驗的行為學數(shù)據(jù)(mean?±?SEM)??指標?AdoC?AdoS?AdoS+M?F?P?AduC?AduS?AduS+M?F?尸??平臺區(qū)穿越次?3.90±?1.90±?4.20±?6.658?0.004?4.00±?1.70±?4.30±?8.252?0.002??數(shù)(次)?0.48?0.38^?0.57“?0.67?0.37#?0.40"??目標象限穿
【參考文獻】:
期刊論文
[1]Neuroinflammation and cytokine abnormality in major depression:Cause or consequence in that illness?[J]. Sang Won Jeon,Yong Ku Kim. World Journal of Psychiatry. 2016(03)
本文編號:3001410
【文章來源】:山東大學山東省 211工程院校 985工程院校 教育部直屬院校
【文章頁數(shù)】:147 頁
【學位級別】:博士
【部分圖文】:
圖1.1實驗范式圖??
?山東大學博士學位論文???A?B??_?100-1?”?100-]??卜n?i?Hi■卜ft?i円i??I-?i|?nl?I-?-I?-i??JJlll?^llJul?JJIJI??///?///?///?///??C?D??40-1?*??一?15.??Iw??J?■*?円???i:ljaMni??/?//?/?//?/,/?/?//??E??0.5-1?*?.??,n;?fi?&?i??i:?n|??::JL?I??/,/?/</??圖1.2青少年期慢性不可預知性應激對青少年和成年大鼠抑郁樣焦慮樣行為的影??響。??Fig.1.2?Effects?of?CUMS?on?the?depressive-?and?anxietj-like?behaviors?of??adolescent?and?adult?rats.?(A)?Sucrose?preference?percentage?in?the?SPT;?(B)??Number?of?crossing?in?the?OFT;?(C)?Number?of?rearing?in?the?OFT;?(D)?Number?of??40??
?山東大學博士學位論文???A?B??*g6-|?^?60-??mAM{Jnl??/?/?/?一?</?/?/?/?/?/?/??圖1.3青少年期慢性不可預知性應激對青少年和成年大鼠空間學習記憶功能的影??響。??Fig.1.3?Effects?of?CUMS?on?the?spatial?learning?and?memory?ability?of?adolescent??and?adult?rats.?(A)?Number?of?crossings?of?the?platform?in?the?MWM?test;?(B)?Target??quadrant?entries?percentage?in?the?MWM?test.?Results?were?expressed?as?the?mean?±??SEM?(n=10?each?group).?#?and?##?indicate?P?<?0.05?and?P?<?0.01?vs.?C?group,??respectively;?and?**?indicate?P?<?0.05?and?P?<?0.01?vs.?S?group,?respectively.??表1-2各組大鼠Morris水迷宮實驗的行為學數(shù)據(jù)(mean?±?SEM)??指標?AdoC?AdoS?AdoS+M?F?P?AduC?AduS?AduS+M?F?尸??平臺區(qū)穿越次?3.90±?1.90±?4.20±?6.658?0.004?4.00±?1.70±?4.30±?8.252?0.002??數(shù)(次)?0.48?0.38^?0.57“?0.67?0.37#?0.40"??目標象限穿
【參考文獻】:
期刊論文
[1]Neuroinflammation and cytokine abnormality in major depression:Cause or consequence in that illness?[J]. Sang Won Jeon,Yong Ku Kim. World Journal of Psychiatry. 2016(03)
本文編號:3001410
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