Role of neuroinflammation in hypertension-induced brain amyloid pathology
Role of neuroinflammation in hypertension-induced brain amyloid pathology
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DOI：
10.1016/j.neurobiolaging.2010.08.013
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Minghetti, Luisa
中科院分区：
文献类型：
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作者：
Carnevale, Daniela;Mascio, Giada;Minghetti, Luisa
高血压和散发性阿尔茨海默病（AD）已被关联，但尚未证明明确的病理生理学联系。高血压和AD具有共同的炎症病理生理特征。因此，我们探讨了调节神经炎症是否可以影响高血压诱导的β-淀粉样蛋白（A β）沉积。高血压，炎症和A β沉积之间可能的相互作用进行了研究，在高血压小鼠横主动脉缩窄（TAC）。考虑到脑A β沉积早在TAC后4周就可检测到，在3周TAC小鼠中、在A β沉积之前和在稍后的时间（8周TAC小鼠）中分析脑病理学。在稍后的时间，沿着明显的A β沉积，小胶质细胞仍然被激活。最后，免疫系统刺激（LPS）或抑制（布洛芬），积极或消极地调节神经炎症的策略，不同地影响A β deposition.We表明，高血压本身触发神经炎症前A β沉积。只有免疫系统激活而不是其抑制强烈降低淀粉样蛋白负荷的发现表明，在适当的时间窗内刺激炎症可能代表限制血管触发的AD病理学的有希望的策略。(C)2012 Elsevier Inc. All rights reserved.
Hypertension and sporadic Alzheimer's disease (AD) have been associated but clear pathophysiological links have not yet been demonstrated. Hypertension and AD share inflammation as a pathophysiological trait. Thus, we explored if modulating neuroinflammation could influence hypertension-induced beta-amyloid (A beta) deposition.Possible interactions among hypertension, inflammation and A beta-deposition were studied in hypertensive mice with transverse aortic coarctation (TAC). Given that brain A beta deposits are detectable as early as 4 weeks after TAC, brain pathology was analyzed in 3-week TAC mice, before A beta deposition, and at a later time (8-week TAC mice).Microglial activation and interleukin (IL)-1 beta upregulation were already found in 3-week TAC mice. At a later time, along with evident A beta deposition, microglia was still activated. Finally, immune system stimulation (LPS) or inhibition (ibuprofen), strategies described to positively or negatively modulate neuroinflammation, differently affected A beta deposition.We demonstrate that hypertension per se triggers neuroinflammation before A beta deposition. The finding that only immune system activation, but not its inhibition, strongly reduced amyloid burden suggests that stimulating inflammation in the appropriate time window may represent a promising strategy to limit vascular-triggered AD-pathology. (C) 2012 Elsevier Inc. All rights reserved.