Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.
Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.
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野生型和阿尔茨海默氏病的类似疾病的APP/PS1小鼠衰老期间的胶质血管变化。
DOI：
10.1016/j.brainres.2015.04.056
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发表时间：
2015-09-16
期刊：
影响因子：
2.9
通讯作者：
Brito MA
中科院分区：
文献类型：
--
作者：
Janota CS;Brites D;Lemere CA;Brito MA
血管和神经胶质参与神经退行性疾病的发展，如阿尔茨海默病（AD），和年龄相关的大脑脆弱性已被提出。因此，我们力求：i）研究哪些血管和神经胶质事件在衰老和/或AD中是明显的，ii）确定AD样和野生型（WT）小鼠中血管和神经胶质变化的时间演变，iii）将其与淀粉样蛋白-β（Aβ）蓄积相关。我们用化学方法检测了APP/PS1 dE 9和WT C57 BL/6小鼠沿着衰老和疾病进展（成年期、中年期和老年期）的大脑皮层和皮质。衰老导致晚期糖基化终产物受体表达增加，以及凝血酶和白蛋白进入海马实质。相比之下，血小板衍生生长因子受体-β（PDGFR-β）阳性细胞的损失，在这两个地区，只与AD发病机制。海马血管形成受到衰老和AD的影响，但这是两种因素在皮质中相互作用的结果。星形胶质细胞增生是海马中AD和皮质中两种因素的结果，而小胶质细胞增生与AD样小鼠中的纤维状淀粉样斑块以及每个研究区域中两种因素之间的相互作用相关。总之，这些数据表明，老年斑仅在海马中先于血管和神经胶质改变，而在皮质中，血管和神经胶质改变，即PDGFR-β阳性细胞的损失和星形胶质细胞增生，伴随着第一个老年斑。因此，这项研究指出血管和神经胶质事件与AD发病机制和年龄相关的大脑脆弱性共存。
Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer’s disease (AD), and age-related brain vulnerabilities has been suggested. Therefore, we sought to: i) investigate which vascular and glial events are evident in ageing and/or AD, ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and iii) to relate them to amyloid-β (Aβ) accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampus parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and by both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations just in hippocampus, whereas in cortex, vascular and glial alterations, namely loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist with AD pathogenesis and age-related brain vulnerabilities.