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水通道蛋白1、4和9在多種朊病毒疾病大腦中的表達(dá)顯著增強(qiáng)

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發(fā)表時(shí)間：2024-09-04 15:55

2019年8月，中國(guó)疾病預(yù)防控制中心病毒病預(yù)防控制所；傳染病預(yù)防控制國(guó)家重點(diǎn)實(shí)驗(yàn)室；傳染病診治協(xié)同創(chuàng)新中心(浙江大學(xué))；首都醫(yī)科大學(xué)附屬北京友誼醫(yī)院神經(jīng)內(nèi)科；中國(guó)疾病預(yù)防控制中心全球公共衛(wèi)生中(State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University),National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Center for Global Public Health, Chinese Center for Disease Control and Prevention, Beijing, China) Cao Chen老師研究團(tuán)隊(duì)在《Prion》上發(fā)表論文：

“Significant enhanced expressions of aquaporin-1, -4 and -9 in the brains of various prion diseases”

“水通道蛋白1、4和9在多種朊病毒疾病大腦中的表達(dá)顯著增強(qiáng)”

Abstract：

Aquaporins (AQPs) are widely expressed in various types of tissues, among them AQP1, AQP4 and AQP9 are expressed predominately with relatively special distributing features in various brain regions. The aberrant changes of AQP1 and AQP4 have been observed in the brains of Alzheimer disease (AD). To evaluate the underlying alteration of brain AQPs in prion diseases, scrapie strains of 139A, ME7 and S15 infected mice were tested in this study. Western blots revealed markedly increased levels of AQP1, AQP4 and AQP9 in the brain tissues of all tested scrapie-infected mice collected at terminal stage. Analyses of the AQPs levels in the brain tissues collected at different time-points during incubation period showed time-dependent increased in 139A and ME7-infected mice, especially at the middle-late stage. The AQP1 levels also increased in the cortex regions of some human prion diseases, including the patients with sporadic Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and G114V genetic CJD (gCJD). Immunohistochemistry (IHC) assays verified that the AQPs-positive cells were astrocyte-like morphologically; meanwhile, numerous various sizes of AQPs-positive particles and dots were also observable in the brain sections of scrapie-infected mice. Immunofluorescent assays (IFAs) illustrated that the signals of AQPs colocalized with those of the GFAP positive proliferative astrocytes, and more interestingly, appeared to overlap also with the signals of PrP in the brains of scrapie-infected mice. Moreover, IHC assays with a commercial doublestain system revealed that distributing areas of AQPs overlapped not only with that of the activated large astrocytes, but also with that of abundantly deposited PrP^Sc
in the brain tissues of scrapie murine models. Our data here propose the solid evidences that the expressions of brain AQP1, AQP4 and AQP9 are all aberrantly enhanced in various murine models of scrapie infection. The closely anatomical association between the accumulated AQPs and deposited PrP^Sc
in the brain tissues indicates that the abnormally increased water channel proteins participate in the pathogenesis of prion diseases.

摘要：

水通道蛋白(Aquaporins, AQPs)廣泛表達(dá)于各類組織中，其中AQP1、AQP4和AQP9在腦各區(qū)域的表達(dá)占主導(dǎo)地位，分布特征相對(duì)特殊。AQP1和AQP4在阿爾茨海默病(AD)大腦中出現(xiàn)異常變化。為了評(píng)估朊病毒疾病中腦AQPs的潛在改變，本研究對(duì)139A、ME7和S15感染小鼠的癢病菌株進(jìn)行了檢測(cè)。Western blot結(jié)果顯示，所有被檢測(cè)的瘙癢病晚期小鼠腦組織AQP1、AQP4和AQP9水平均顯著升高。對(duì)139A和me7感染小鼠在孵育期間不同時(shí)間點(diǎn)腦組織AQPs水平的分析顯示，AQPs水平呈時(shí)間依賴性升高，尤其是在中晚期。在散發(fā)性克雅氏病(CJD)、致死性家族性失眠癥(FFI)和G114V遺傳性CJD (gCJD)患者等人類朊病毒疾病的皮質(zhì)區(qū)，AQP1水平也有所升高。免疫組化(IHC)檢測(cè)證實(shí)aqps陽(yáng)性細(xì)胞形態(tài)呈星形細(xì)胞樣;同時(shí)，在瘙癢病小鼠腦切片中也觀察到大量不同大小的aqps陽(yáng)性顆粒和點(diǎn)。免疫熒光分析(IFAs)表明AQPs的信號(hào)與GFAP陽(yáng)性的增殖性星形膠質(zhì)細(xì)胞的信號(hào)共定位，更有趣的是，在瘙癢病感染小鼠的大腦中，AQPs的信號(hào)似乎也與PrP的信號(hào)重疊。此外，用商業(yè)雙染色系統(tǒng)進(jìn)行的免疫組化檢測(cè)顯示，在癢病小鼠模型腦組織中，AQPs的分布區(qū)域不僅與活化的大星形膠質(zhì)細(xì)胞重疊，而且與大量沉積的PrPSc重疊。研究人員的數(shù)據(jù)提供了有力的證據(jù)，證明腦AQP1、AQP4和AQP9的表達(dá)在各種小鼠瘙癢病感染模型中都異常增強(qiáng)。腦組織中積累的aqp與沉積的PrPSc之間的密切解剖學(xué)關(guān)聯(lián)表明，異常增加的水通道蛋白參與了朊病毒疾病的發(fā)病機(jī)制。