Enhanced expression of glia maturation factor correlates with glial activation in the brain of triple transgenic Alzheimer's disease mice.

Enhanced expression of glia maturation factor correlates with glial activation in the brain of triple transgenic Alzheimer's disease mice.
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DOI:
10.1007/s11064-012-0913-z
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发表时间:
2013-01
影响因子:
4.4
通讯作者:
Zaheer, Asgar
Zaheer, Asgar
中科院分区:
医学3区
文献类型:
--
作者:
Zaheer, Smita;Thangavel, Ramasamy;Wu, Yanghong;Khan, Mohammad Moshahid;Kempuraj, Duraisamy;Zaheer, Asgar

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我们以前证明,胶质细胞成熟因子(GMF),脑特异性蛋白质,分离,测序和克隆在我们的实验室,诱导表达的促炎细胞因子和趋化因子在中枢神经系统(CNS)。我们还报道了GMF在星形胶质细胞中的上调导致神经元的破坏,提示GMF介导的脑细胞毒性的新途径,并暗示其参与炎性神经退行性疾病的发病机制。在本研究中,我们研究了三转基因阿尔茨海默病(3xTg-AD)小鼠中GMF的表达。我们的结果显示,GMF上调13倍,促炎细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-1β、干扰素γ(IFN-γ)上调8-12倍,和趋化因子(C-C基序)配体2(CCL 2)和C-X-C基序趋化因子10图10显示了与非转基因(Non-Tg)小鼠相比,通过定量实时RT-PCR测定的3xTg-AD小鼠脑中的CXCL 10/IP-10 mRNA的表达。总之,GMF和细胞因子/趋化因子表达的增加与3xTg-AD小鼠中反应性胶质细胞酸性蛋白(GFAP)阳性星形胶质细胞和离子钙结合衔接分子1(Iba-1)阳性小胶质细胞相关。
We previously demonstrated that glia maturation factor (GMF), a brain specific protein, isolated, sequenced and cloned in our laboratory, induce expression of proinflammatory cytokines and chemokines in the central nervous system (CNS). We also reported that the up-regulation of GMF in astrocytes leads to the destruction of neurons suggesting a novel pathway of GMF-mediated cytotoxicity of brain cells, and implicated its involvement in the pathogenesis of inflammatory neurodegenerative diseases. In the present study, we examined the expressions of GMF in triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Our results show a 13-fold up-regulation of GMF and 8–12-fold up-regulation of pro inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, interferon gamma (IFN-γ), and chemokine (C-C motif) ligand 2 (CCL2) and C-X-C motif chemokine 10 (CXCL10/IP-10) mRNA as determined by quantitative real-time RT-PCR in the brain of 3xTg-AD mice as compared to non-transgenic (Non-Tg) mice. In conclusion, the increase in GMF and cytokine/chemokine expression was correlated with reactive glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglia in 3xTg-AD mice.
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发表时间: 2012-10
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DOI: 10.1073/pnas.86.10.3901
发表时间: 1989-05-01
影响因子: 11.1
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发表时间: 2012-05-01
影响因子: 3.8
作者:
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通讯作者: Roberson ED