中华神经医学杂志
中華神經醫學雜誌
중화신경의학잡지
Chinese Journal of Neuromedicine
2015年
8期
799-804
,共6页
王正玉%韩振敏%唐伟%姚余有
王正玉%韓振敏%唐偉%姚餘有
왕정옥%한진민%당위%요여유
产前应激%慢性应激%真核翻译起始因子2的α亚单位%蛋白激酶R样内质网激酶%葡萄糖调节蛋白78%淀粉样前体蛋白β位点分裂酶1
產前應激%慢性應激%真覈翻譯起始因子2的α亞單位%蛋白激酶R樣內質網激酶%葡萄糖調節蛋白78%澱粉樣前體蛋白β位點分裂酶1
산전응격%만성응격%진핵번역기시인자2적α아단위%단백격매R양내질망격매%포도당조절단백78%정분양전체단백β위점분렬매1
Prenatal stress%Chronic stress%Eukaryotic initiation factor 2α%Protein kinase R [PKR]-like ER kinase%Glucose-regulated protein 78%Beta-site APP-cleaving enzyme 1
目的 探讨产前应激是否能促进慢性应激诱导的6月龄雄性子代鼠海马β-淀粉样蛋白(Aβ)形成及其作用机制. 方法 以APPswe/PS1 dE9双转基因小鼠为研究对象,将雄性APPswe/PS1 dE9双转基因子代鼠根据产前是否应激和子代鼠是否慢性应激分为产前应激-子代慢性应激(TT)组、产前应激-子代正常处理(TC)组、产前正常处理-子代慢性应激(CT)组和产前正常处理-子代正常处理(CC)组,每组18只.采用刚果红染色检查子代鼠脑组织的淀粉样斑块;采用Western blotting检测海马组织磷酸化真核翻译起始因子2的α亚单位(p-eIF2α)、磷酸化蛋白激酶R样内质网激酶(p-PERK)、葡萄糖调节蛋白78(Grp78)和淀粉样前体蛋白β位点分裂酶1(BACE1)的表达水平;采用ELISA法检测Aβ1-40和Aβ1-42表达水平;采用荧光酶标仪检测BACE1活性. 结果 与CC组相比,CT组、TT组、TC组小鼠脑组织淀粉样斑块数目增多.与CC组相比,CT组小鼠海马组织p-eIF2α、p-PERK、Grp78、BACE1、Aβ1-40和Aβ1-42表达水平明显升高,差异均有统计学意义(P＜0.05).与CT组相比,TT组海马组织p-eIF2α、p-PERK、Grp78、BACE1、Aβ1-40和Aβ1-42表达水平进一步升高,差异均有统计学意义(P＜0.05).各组小鼠海马组织BACE1活性比较差异无统计学意义(P＞0.05). 结论 产前应激可促进慢性应激诱导的6月龄雄性APPswe/PS1 dE9双转基因小鼠子代鼠Aβ生成增多,其机制可能是产前应激通过促进子代鼠海马神经元内质网应激,激活PERK,引起eIF2α磷酸化,促进BACE1表达增加,从而促进Aβ生成.
目的 探討產前應激是否能促進慢性應激誘導的6月齡雄性子代鼠海馬β-澱粉樣蛋白(Aβ)形成及其作用機製. 方法 以APPswe/PS1 dE9雙轉基因小鼠為研究對象,將雄性APPswe/PS1 dE9雙轉基因子代鼠根據產前是否應激和子代鼠是否慢性應激分為產前應激-子代慢性應激(TT)組、產前應激-子代正常處理(TC)組、產前正常處理-子代慢性應激(CT)組和產前正常處理-子代正常處理(CC)組,每組18隻.採用剛果紅染色檢查子代鼠腦組織的澱粉樣斑塊;採用Western blotting檢測海馬組織燐痠化真覈翻譯起始因子2的α亞單位(p-eIF2α)、燐痠化蛋白激酶R樣內質網激酶(p-PERK)、葡萄糖調節蛋白78(Grp78)和澱粉樣前體蛋白β位點分裂酶1(BACE1)的錶達水平;採用ELISA法檢測Aβ1-40和Aβ1-42錶達水平;採用熒光酶標儀檢測BACE1活性. 結果 與CC組相比,CT組、TT組、TC組小鼠腦組織澱粉樣斑塊數目增多.與CC組相比,CT組小鼠海馬組織p-eIF2α、p-PERK、Grp78、BACE1、Aβ1-40和Aβ1-42錶達水平明顯升高,差異均有統計學意義(P＜0.05).與CT組相比,TT組海馬組織p-eIF2α、p-PERK、Grp78、BACE1、Aβ1-40和Aβ1-42錶達水平進一步升高,差異均有統計學意義(P＜0.05).各組小鼠海馬組織BACE1活性比較差異無統計學意義(P＞0.05). 結論 產前應激可促進慢性應激誘導的6月齡雄性APPswe/PS1 dE9雙轉基因小鼠子代鼠Aβ生成增多,其機製可能是產前應激通過促進子代鼠海馬神經元內質網應激,激活PERK,引起eIF2α燐痠化,促進BACE1錶達增加,從而促進Aβ生成.
목적 탐토산전응격시부능촉진만성응격유도적6월령웅성자대서해마β-정분양단백(Aβ)형성급기작용궤제. 방법 이APPswe/PS1 dE9쌍전기인소서위연구대상,장웅성APPswe/PS1 dE9쌍전기인자대서근거산전시부응격화자대서시부만성응격분위산전응격-자대만성응격(TT)조、산전응격-자대정상처리(TC)조、산전정상처리-자대만성응격(CT)조화산전정상처리-자대정상처리(CC)조,매조18지.채용강과홍염색검사자대서뇌조직적정분양반괴;채용Western blotting검측해마조직린산화진핵번역기시인자2적α아단위(p-eIF2α)、린산화단백격매R양내질망격매(p-PERK)、포도당조절단백78(Grp78)화정분양전체단백β위점분렬매1(BACE1)적표체수평;채용ELISA법검측Aβ1-40화Aβ1-42표체수평;채용형광매표의검측BACE1활성. 결과 여CC조상비,CT조、TT조、TC조소서뇌조직정분양반괴수목증다.여CC조상비,CT조소서해마조직p-eIF2α、p-PERK、Grp78、BACE1、Aβ1-40화Aβ1-42표체수평명현승고,차이균유통계학의의(P＜0.05).여CT조상비,TT조해마조직p-eIF2α、p-PERK、Grp78、BACE1、Aβ1-40화Aβ1-42표체수평진일보승고,차이균유통계학의의(P＜0.05).각조소서해마조직BACE1활성비교차이무통계학의의(P＞0.05). 결론 산전응격가촉진만성응격유도적6월령웅성APPswe/PS1 dE9쌍전기인소서자대서Aβ생성증다,기궤제가능시산전응격통과촉진자대서해마신경원내질망응격,격활PERK,인기eIF2α린산화,촉진BACE1표체증가,종이촉진Aβ생성.
Objective To explore whether prenatal stress promotes formation of chronic stress-induced hippocampal amyloid β (Aβ) protein in 6-month-old male offspring mice and its mechanism.Methods The APPswe/PSIdE9 double transgenic mice were divided into 4 groups according to the prenatal stress and offspring mice stress:prenatal control-offspring control group (CC group),prenatal control-chronic offspring stress group (CT group),chronic prenatal stress-offspring control group (TC group),and chronic prenatal stress-chronic offspring stress group (TT group) (n=18).The number of amyloid plaques in brains was checked using Congo red staining.ELISA was used to examine the hippocampus levels ofamyloid-β proteins (Aβ1-42 and Aβ1-40) in the offspring mice;β-site APP-cleaving enzyme 1 (BACE1) activity was detected using fluorospectrophotometry.Additionally,Western blotting were used to observe the expression levels of phosphorylated eukaryotic initiation factor 2α (p-eIF2α),phosphorylated protein kinase R [PKR]-like ER kinase (p-PERK),glucose-regulated protein 78 (Grp78) and β-site BACE1 in the hippocampus.Results As compared with that in the CC group,the number of amyloid plaques in brain in CT,TT and TC groups was increased.The expressions of p-eIF2α,p-PERK,Grp78,BACE1,Aβ1-40 and Aβ1-42 in the hippocampus of CT group were significantly increased as compared with those in the CC group (P＜0.05).The expressions of p-eIF2α,p-PERK,Grp78,BACE1,Aβ1-40 and Aβ1-42 in the hippocampus of TT group were further significantly increased as compared with those in the CT group (P＜0.05).There was no significant difference in BACE1 activity among the different groups (P＞0.05).Conclusion The prenatal stress can promote the formation of hippocampal Aβ protein induced by chronic stress in 6-month-old male offspring mice,whose mechanism may be that prenatal stress aggravates hippocampal neurons endoplasmic reticulum stress,activates the PERK,then causes eIF2 alpha phosphorylation,and finally promotes BACE1 expression.
