Decreased hippocampal cell proliferation correlates with increased expression of BMP4 in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease
Decreased hippocampal cell proliferation correlates with increased expression of BMP4 in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease
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DOI：
10.1002/hipo.20428
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Yang, Li
中科院分区：
文献类型：
--
作者：
Li, Dabing;Tang, Jun;Yang, Li
已经在阿尔茨海默病(AD)转基因(TG)小鼠模型中发现了海马细胞增殖的变化；然而，对其潜在机制知之甚少。在此之前，我们已经证明了在戊四氮点燃癫痫模型中，齿状回(DG)中BMP4的含量影响海马细胞的增殖。在本研究中，我们评估了APPswe/PS1 Delta E9 TG小鼠的海马细胞增殖和BMP4 mRNA水平，APPswe/PS1 Delta E9 TG小鼠是一种成熟的小鼠模型，在该模型中，家族性AD相关APP“瑞典”(APPswe)和PS1 Delta E9多肽变体的共同表达导致Aβ在海马区和皮质中沉积。9月龄和12月龄APPswe/PS1 Delta E9TG小鼠DG颗粒下带(DG-SGZ)的BrdU标记细胞数明显少于同龄非转基因仔鼠，而Tg小鼠BMP4mRNA水平显著升高。BMP4基因表达增加与BrdU标记细胞数量减少呈正相关。在用反义寡核苷酸(ASODN)有效地阻断内源性BMP4的表达后，9月龄和12月龄TG小鼠DGSGZ和门区海马区细胞增殖的减少被逆转。提示APPsWE/PS1 Delta E9TG小鼠海马齿状回BMP4基因表达增加可能是其细胞增殖能力下降的原因之一。(C)2008年Wiley-Liss，Inc.
Alterations in hippocampal cell proliferation have been identified in transgenic (tg) mouse models of Alzheimer's disease (AD); however, relatively little is known about the underlying mechanisms. Previously, we have demonstrated that enclogenous level of BMP4 in the dentate gyrus (DG) affects hippocampal cell proliferation in a pentylentetrazol kindling-induced epilepsy model. In the present study, we evaluated hippocampal cell proliferation and BMP4 mRNA level in the APPswe/PS1 Delta E9 tg mouse, a well-established mouse model in which coexpression of familial AD-linked APP "Swedish" (APPswe) and PS1 Delta E9 polypeptide variants leads to A beta deposition throughout the hippocampus and cortex. The number of bromodeoxyuricline (BrdU)labeled cells in the DG subgranular zone (DG-SGZ) of 9- and 12-month-old APPswe/PS1 Delta E9 tg mice was markedly reduced compared with age-matched nontransgenic littermates, whereas, the BMP4 mRNA level was significantly increased in the tg mice. There was a significant correlation between the increased BMP4 mRNA expression and the decreased number of BrdU labeled cells. After effectively blocking the expression of endogenous BMP4 with antisense oligodeoxynucleotides (ASODN), the decrease in hippocampal cell proliferation in the DGSGZ and hilus of 9- and 12-month-old tg mice was reversed. These findings suggest that the increased expression of BMP4 mRNA within the DG of the hippocampus may contribute to the decrease in cell proliferation in APPswe/PS1 Delta E9 tg mice. (C) 2008 Wiley-Liss, Inc.