Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice.
Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice.
复制标题
3XTG-AD转基因小鼠的胆碱营养基础前脑系统改变。
DOI：
10.1016/j.nbd.2010.10.002
复制
发表时间：
2011-02
影响因子：
6.1
通讯作者：
Mufson, Elliott J.
中科院分区：
文献类型：
--
作者：
Perez, Sylvia E.;He, Bin;Muhammad, Nadeem;Oh, Kwang-Jin;Fahnestock, Margaret;Ikonomovic, Milos D.;Mufson, Elliott J.
关键词：
依赖于神经生长因子及其受体生存的胆碱能系统在阿尔茨海默病（AD）中选择性地脆弱。但是，几乎没有人知道这种缺陷是如何发展的，与这种疾病的标志性病变，淀粉样蛋白斑块和含tau蛋白的神经元缠结有关。绝大多数用于评估β淀粉样蛋白（Aβ）沉积对胆碱能系统影响的AD转基因模型过度表达淀粉样蛋白前体蛋白（APP）。然而，对于该系统在三重转基因（3xTg）-AD小鼠中如何受到影响还一无所知，这是一种在皮质和海马中显示Aβ斑块和缠结样病理学的AD动物模型，其接受广泛的胆碱能神经支配。我们对年轻（2-4个月）、中年（13-15个月）和老年（18-20个月）3xTg-AD小鼠的胆碱营养系统进行了详细的形态学和生化表征。胆碱能神经炎性髓鞘的数量和大小随着年龄的增长而增加，老年雌性小鼠的海马-下托复合体比3xTg-AD雄性小鼠更明显。体视学分析显示，减少胆碱乙酰转移酶（ChAT）阳性细胞的内侧隔/垂直肢体的斜角带的Broca在老年3xTg-AD小鼠。与年龄匹配的ntg小鼠相比，中年3xTg-AD小鼠海马中的ChAT酶活性水平显著降低。ProNGF蛋白水平在老年3xTg-AD小鼠的皮质中增加，而TrkA蛋白水平在老年突变小鼠中以性别依赖的方式降低。与此相反，p75 NTR蛋白质皮质水平是稳定的，但增加了老年3xTg-AD小鼠的海马。这些数据表明，3xTg-AD小鼠中的促胆碱能改变具有年龄和性别依赖性，并且在海马中更明显，海马是一种受Aβ斑块病理学影响更严重的结构。
The cholinotrophic system, which is dependent upon nerve growth factor and its receptors for survival, is selectively vulnerable in Alzheimer's disease (AD). But, virtually nothing is known about how this deficit develops in relation to the hallmark lesions of this disease, amyloid plaques and tau containing neurofibrillary tangles. The vast majority of transgenic models of AD used to evaluate the effect of beta amyloid (Aβ) deposition upon the cholinotrophic system over-express the amyloid precursor protein (APP). However, nothing is known about how this system is affected in triple transgenic (3xTg)-AD mice, an AD animal model displaying Aβ plaque- and tangle-like pathology in the cortex and hippocampus, which receive extensive cholinergic innervation. We performed a detailed morphological and biochemical characterization of the cholinotrophic system in young (2-4 months), middle-aged (13-15 months), and old (18-20 months) 3xTg-AD mice. Cholinergic neuritic swellings increased in number and size with age, and were more conspicuous in the hippocampal-subicular complex in aged female than in 3xTg-AD male mice. Stereological analysis revealed a reduction in choline acetyltransferase (ChAT) positive cells in the medial septum/vertical limb of the diagonal band of Broca in aged 3xTg-AD mice. ChAT enzyme activity levels decreased significantly in the hippocampus of middle-aged 3xTg-AD mice compared to age-matched ntg mice. ProNGF protein levels increased in the cortex of aged 3xTg-AD mice, whereas TrkA protein levels were reduced in a gender-dependent manner in aged mutant mice. In contrast, p75NTR protein cortical levels were stable but increased in the hippocampus of aged 3xTg-AD mice. These data demonstrate that cholinotrophic alterations in 3xTg-AD mice are age and gender dependent and more pronounced in the hippocampus, a structure more severely affected with Aβ plaque pathology.
登录
查看更多内容
影响因子：
3.3
作者：
Aucoin, JS;Jiang, P;Hamel, E
通讯作者：
Hamel, E
影响因子：
4.7
作者：
Chen, L;Yamada, K;Sokabe, M
通讯作者：
Sokabe, M
DOI：
10.1097/nen.0b013e3181aed9e6
发表时间：
2009-08-01
影响因子：
3.2
作者：
Bruno, Martin A.;Leon, Wanda C.;Cuello, A. Claudio
通讯作者：
Cuello, A. Claudio
DOI：
10.1093/jnen/62.2.137
发表时间：
2003-02-01
影响因子：
3.2
作者：
D'Amore, JD;Kajdasz, ST;Hyman, BT
通讯作者：
Hyman, BT
影响因子：
2.5
作者：
AMARAL, DG;KURZ, J
通讯作者：
KURZ, J