The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease
The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease
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DOI：
10.1016/j.expneurol.2015.02.034
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发表时间：
2015-05-01
影响因子：
5.3
通讯作者：
Vickers, James C.
中科院分区：
文献类型：
--
作者：
Collins, Jessica M.;King, Anna E.;Vickers, James C.
创伤性脑损伤是阿尔茨海默病（AD）的危险因素，然而，这种神经损伤对β-淀粉样蛋白（A β）斑块病理学的发作和进展的影响尚未得到充分了解。本研究利用局灶性脑损伤的体内模型来检查局部损伤如何可能急性影响A β斑块沉积的发作和进展以及炎症和突触变化，在AD的APP/PS1（APP（SWE），PSEN 1dE 9）转基因模型中相对于野生型（Wt）小鼠。急性局灶性脑损伤在3个月和9个月大的APP/PS1和Wt小鼠的诱导通过插入一根针到躯体感觉新皮层，与假手术相比，并检查在24小时和7天后损伤（PI）。在3月龄APP/PS1小鼠或Wt小鼠中，局灶性脑损伤在PI 24 h或7 d均未诱导硫代嘌呤-S染色或（泛A β抗体）MOAB-2标记的斑块。9个月大的APP/PS1小鼠表现出皮质A β斑块，但在PI 24 h或PI 7 d，局灶性损伤对损伤部位周围的硫代嘌呤-S或MOAB-2斑块负荷没有统计学显著（p > 0.05）影响。与假手术动物相比，受损小鼠中lba-1阳性小胶质细胞占据的横截面皮质面积显著增加（p < 0.001），然而，APP/PS1和Wt小鼠之间的这种反应没有差异（p > 0.05）。对于Wt和APP/PS1小鼠，损伤部位附近的突触体蛋白斑点在PI 24小时显著减少（与远离损伤的部位和假手术小鼠中的相应区域相比; p < 0.01），但在PI 7天后不显著减少（p > 0.05）。基因型对该反应无显著影响（p > 0.05）。这些结果表明，局灶性脑损伤和相关的小胶质细胞反应不会急性改变APP/PS1小鼠模型中的A β斑块沉积。此外，目前的研究表明，Wt和APP/PS1小鼠的大脑都能够恢复损伤后失去的突触素免疫反应性，后者在A β斑块病理的存在下导致突触变性。(C)2015 Elsevier Inc. All rights reserved.
Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (A beta) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of A beta plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APP(SWE), PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24 h and 7 d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-A beta antibody) MOAB-2-labeled plaques at either 24 h or 7 d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical A beta plaques but focal injury had no statistically significant (p > 0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24 h PI or 7 d PI. There was a significant (p < 0.001) increase in cross-sectional cortical area occupied by lba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p > 0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24 h PI (compared to sites distant to the injury and the corresponding area in sham mice; p < 0.01), but not after 7 d PI (p > 0.05). There was no significant effect of genotype on this response (p > 0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter A beta plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of A beta plaque pathology that causes synaptic degeneration. (C) 2015 Elsevier Inc. All rights reserved.