IGF2 ameliorates amyloidosis, increases cholinergic marker expression and raises BMP9 and neurotrophin levels in the hippocampus of the APPswePS1dE9 Alzheimer's disease model mice.
IGF2 ameliorates amyloidosis, increases cholinergic marker expression and raises BMP9 and neurotrophin levels in the hippocampus of the APPswePS1dE9 Alzheimer's disease model mice.
复制标题
DOI：
10.1371/journal.pone.0094287
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Blusztajn JK
中科院分区：
文献类型：
--
作者：
Mellott TJ;Pender SM;Burke RM;Langley EA;Blusztajn JK
开发一种有效的治疗阿尔茨海默病（AD）的方法是生物医学科学面临的一个重大挑战。由于早期阿尔茨海默病的病理生理包括海马异常，一种可行的治疗策略可能是使用支持海马完整性和功能的营养因子。IGF2是一个有吸引力的候选者，因为它在海马体中起作用，增强记忆巩固，刺激成人神经发生，上调胆碱能标志物表达和乙酰胆碱（ACh）释放。我们对转基因APPswe进行了为期7天的脑室内IGF2输注。在胆碱能神经元（APP.PS1/CHGFP）和野生型WT/CHGFP幼仔中表达绿色荧光蛋白的PS1dE9 AD模型小鼠，6月龄代表早期AD样疾病。IGF2可减少APP.PS1/CHGFP小鼠海马a - β40和a - β42阳性淀粉样斑块的数量。此外，IGF2增加了WT/CHGFP和APP.PS1/CHGFP小鼠海马中乙酰胆碱转移酶和乙酰胆碱合成酶的蛋白水平。后一种效应可能是由与对照组相比，在igf2处理的小鼠中观察到的胆碱能分化因子BMP9的蛋白表达增加介导的。IGF2还增加了海马NGF、BDNF、NT3和IGF1的蛋白水平，以及双皮质素（神经发生的标志）的蛋白水平。这些数据表明，IGF2可有效逆转和预防与AD相关的几种病理生理过程，并提示IGF2可能构成AD的治疗靶点。
The development of an effective therapy for Alzheimer’s disease (AD) is a major challenge to biomedical sciences. Because much of early AD pathophysiology includes hippocampal abnormalities, a viable treatment strategy might be to use trophic factors that support hippocampal integrity and function. IGF2 is an attractive candidate as it acts in the hippocampus to enhance memory consolidation, stimulate adult neurogenesis and upregulate cholinergic marker expression and acetylcholine (ACh) release. We performed a seven-day intracerebroventricular infusion of IGF2 in transgenic APPswe.PS1dE9 AD model mice that express green fluorescent protein in cholinergic neurons (APP.PS1/CHGFP) and in wild type WT/CHGFP littermates at 6 months of age representing early AD-like disease. IGF2 reduced the number of hippocampal Aβ40- and Aβ42-positive amyloid plaques in APP.PS1/CHGFP mice. Moreover, IGF2 increased hippocampal protein levels of the ACh-synthesizing enzyme, choline acetyltransferase in both WT/CHGFP and APP.PS1/CHGFP mice. The latter effect was likely mediated by increased protein expression of the cholinergic differentiating factor, BMP9, observed in IGF2-treated mice as compared to controls. IGF2 also increased the protein levels of hippocampal NGF, BDNF, NT3 and IGF1 and of doublecortin, a marker of neurogenesis. These data show that IGF2 administration is effective in reversing and preventing several pathophysiologic processes associated with AD and suggest that IGF2 may constitute a therapeutic target for AD.
登录
查看更多内容
影响因子：
16.2
作者：
ALDERSON, RF;ALTERMAN, AL;LINDSAY, RM
通讯作者：
LINDSAY, RM
影响因子：
4.8
作者：
Brown, MA;Zhao, QH;Choe, S
通讯作者：
Choe, S
影响因子：
3.4
作者：
Couillard-Despres, S;Winner, B;Aigner, L
通讯作者：
Aigner, L
影响因子：
6.1
作者：
Garcia-Alloza, Monica;Robbins, Elissa M.;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.
影响因子：
10.6
作者：
Grothe, Michel;Heinsen, Helmut;Teipel, Stefan J.
通讯作者：
Teipel, Stefan J.